Articles concerning Crohns / Colitis

Date: Mon, 08 Mar 1999 02:26:26 -0500
From: "H. Norris" <>
Subject: Nature Magz on gut bacteria

Recent Nature magazine article on gut bacteria biology.
- Holten

Looking after number one


Its astonishing the lengths some bacteria will go to get on in life. When times are hard, enterobacteriacae - the bacteria that colonise our guts - for example, murder their relatives from other strains in order to minimise competition for nutrients. They do so by releasing toxins known as colicins.

One of these, so-called 'endonuclease colicin', kills bacteria by stealing into them via their vitamin B12 receptors and digesting their DNA. But what of the bacteria that actually produces this lethal weapon? How does it protect itself during the toxin production stage, when the deadly colicin could just as easily 'bite the hand that fed it'?

A bacteria protects itself against its own colicin by simultaneously producing an inhibitory protein. The two bind, inactivating the toxin until it is released into the environment.

Now Colin Kleanthous of the University of East Anglia, Norwich , UK, and colleagues have used X-ray crystallography to determine the crystal structure of the complex formed when the DNA-destroying part of one of these colicins,'E9', binds to its inhibitor, 'Im9'. As they announce in Nature Structural Biology [March 1999], they also found that the inhibitor protein averts cell suicide by folding into its active shape within milliseconds - indeed it turns out to be one of the fastest-folding proteins known.

Surprisingly, the structure also shows that Im9 seems to block DNA-digestion in a novel way. Whereas most analogous systems work by plugging the 'active site' (the site where the toxin would lock onto its target) of the unwanted enzyme so that nothing else can dock there, Im9 appears to disable colicin in some alternative fashion that leaves the active site wide open.

Having analysed the structure and electrostatics or the system, Kleanthous' team suspects that Im9 binds to E9 in such a way that it not only hives-off the toxin's essential catalytic 'arms' and but also neutralises the charge density at its active site. Hence anything trying to bind there is electrostatically repelled.

"This hyperefficient mechanism of inhibition could well be suited to other toxic enzyme systems," the group conclude. Moreover since some aspects of mammalian programmed cell death, or 'apoptosis', resemble the colicin system, this toxin-inhibitor system may also be a good model for understanding the various ways in which cells can commit or prevent, suicide.

© Macmillan Magazines Ltd 1999 - NATURE NEWS SERVICE

Nature © Macmillan Publishers Ltd 1999 Registered No. 785998 England.

Date: Sun, 07 Mar 1999 08:00:38 -0500
From: jeff goldschlager <>
Subject: slim pickings

Here's article of interest:

Starchy foods may trigger overeating

NEW YORK, Mar 04 (Reuters Health) -- Eating pasta, white bread, potatoes, and other rapidly digested "starchy" or "sugary" foods may lead to overeating by triggering a hormonal state that convinces the body it is still hungry, researchers report this month in the electronic version of the journal Pediatrics.

Dr. David S. Ludwig of Tufts University in Boston, Massachusetts, and colleagues offered 12 obese teenage boys unlimited snacks several hours after giving them low-, medium-, or high-starch meals.

The low-starch meal consisted of a vegetable omelet and fruit, the medium was unprocessed oatmeal, and the high-starch meal was processed "instant" oatmeal.

All of the meals had the same number of calories.

The boys who had eaten the high-starch instant oatmeal ate 81% more snacks than those who had eaten the low-starch omelet and fruit, the researchers found.

The investigators also found that the blood sugar of these boys had risen sharply and then crashed, triggering hunger.

More Americans are obese now than at any time in recorded history -- approximately 20% of children and more than 33% of adults. The popularity of starchy foods may play a role, Ludwig's team notes.

Although more work needs to be done to determine the optimal healthy diet, the study authors write that "this study suggests possible advantages for treatment of obesity... with abundant quantities of vegetables, legumes, and fruits; decreased amounts of... carbohydrates; and moderate intake of protein and fats."

SOURCE: Pediatrics 1999;103:e26.

Date: Thu, 07 Jan 1999 18:05:03 -0800
From: Tom <>
To: "" <>
Subject: Probiotics article in Time magazine

The following article appeared in Time magazine. It looks like there is
a lot of interest in probiotics.

TIME, DECEMBER 28,1998 - JANUARY 4,1999 Page 197

Healthy Germs
by Christine Gorman

What's the next trend at your health-food store? Bacteria that fight diarrhea and other illnesses
Say the word bacteria, and most folks conjure up images of a nasty germ like staphylococcus or salmonella that can make you really sick. But most bacteria aren't bad for you. In fact, consuming extra amounts of some bacteria can actually promote good health. These beneficial bacteria are available without a prescription in drug and health-food stores and in foods like yogurt. So far, the best results have been seen in the treatment of diarrhea, particularly in children. But researchers are also looking into the possibility that beneficial bacteria may thwart vaginal infections in women, prevent some food allergies in children and lessen symptoms of Crohn's disease, a relatively rare but painful gastrointestinal disorder.

So where have these good germs been lurking all your life? In your intestines, especially the lower section called the colon, which harbors at least 400 species of bacteria. Which ones you have depends largely on your environment and diet. An abundance of good bacteria in the colon generally crowds out stray bad bacteria in your food. But if the bad outnumber the good -- for example, after antibiotic treatment for a sinus or an ear infection, which kills normal intestinal germs as well -- the result can be diarrhea.

For generations, people have restored the balance by eating yogurt, buttermilk or other products made from fermented milk. But nowadays, you can also down a few pills that contain freeze-dried germs. These preparations are called probiotics to distinguish them from antibiotics. Unfortunately, you can't always be sure that the bacteria in the products you buy are the same strains as those listed on the label or even that they're still alive. Probiotics are usually sensitive to both heat and moisture.

Among the most promising and most thoroughly researched probiotics is the CC strain of Lactobacillus, discovered by Dr. Sherwood Gorbach and biochemist Barry Goldin, both at Tufts University School of Medicine. L-GG, as it's called, has been used to treat traveler's diarrhea and intestinal upsets caused by antibiotics. Even more intriguing, L-GG also seems to work against some viruses, including rotavirus, one of the most common causes of diarrhea in children in the U.S. and around the world. Here the effect is indirect. Somehow L-GG jump-starts the immune system into recognizing the threat posed by the virus. In October a subsidiaiy of Con Agra started marketing L-GG under the brand name Culturelle. (For more information, call 888-828-4242.)

Pediatricians at Johns Hopkins are studying a different bug, the Bb-12 strain of Bifidobacterium which was discovered by researchers at CHR Hansen Biosystems. Like L-GG, Bb12 stimulates the immune system. For reasons that are not clear, infants who are breast-fed have large amounts of bifidobacteria in their intestines. They also have fewer intestinal upsets. Dr. Jose Saavedra and colleagues at Hopkins have shown that Bb-12 prevents several types of diarrhea, including that caused by rotavirus, in hospitalized infants as young as four months. It has also been used to cure diarrhea in children of all ages. Products containing Bb-12 are available from Nutraceutical Corp. (800-365-5966), Solgar (800-645-2246) and American Lifeline (800-257-5433), among others.

For more Web resources on probiotics, visit

Paris, Tuesday, March 2, 1999
Can a Person 'Catch' Heart Disease? Maybe
Infectious Microbes Under Suspicion

By Rick Weiss Washington Post Service

WASHINGTON - From gallstones to arthritis to heart disease, many illnesses long presumed to have roots in genes or lifestyle might be caused largely by infectious agents, a growing number of scientists believe.
That prospect is raising the intriguing possibility that people can "catch" kidney stones, cerebral palsy or Alzheimer's disease.
Most of the evidence remains circumstantial. A microbe might be suspiciously present in people who have a disease, for example, and not in those who do not - suggesting, but not proving, causality.
But for some conditions - including heart disease - many scientists feel certain that microbes play at least a contributing role where none previously was suspected. Researchers announced last week that they had discovered a molecular mechanism by which mice can get heart disease from a bacterium. And high-tech tests have been picking up previously undetectable bacterial "fingerprints" in people with other chronic conditions, strengthening the case that microbes are the hidden perpetrators.
The implications of the new theory are enormous, researchers say. Most important, it suggests that vaccines or antibiotics might have an unexpectedly big role to play in the treatment of chronic diseases that today are treated with only modest success through lifestyle changes, such as exercise and improved diet.
"If an infectious agent is responsible for even a portion of these diseases, that could change the outlook for treatment and prevention dramatically," said Barry Bloom, dean of the Harvard School of Public Health. "I see chronic disease as the next frontier for vaccines."
Mr. Bloom and others cautioned against placing too much blame on bacteria. For most chronic diseases, bacteria are probably just part of the puzzle, they said. And widespread, long-term use of powerful antibiotics carries its own problems, including the possible emergence of drug-resistant "superbugs."
"The bacteria by themselves are not going to give us the only useful answers," said Janice Kiecolt-Glaser of Ohio State University, who studies the effects of stress on health. "You could have the bug, and if resistance is altered by stress or other factors, you could be more prone to not healing or to the infection progressing."
Nonetheless, said Anne Schuchat, chief of the respiratory diseases branch at the Centers for Disease Control and Prevention in Atlanta, chronic conditions such as heart disease take such a big toll on society that even a modest contribution by bacteria deserves to be targeted.
The revolution began about five years ago, when definitive evidence arose that stomach ulcers are caused not by excess stomach acid, as had long been presumed, but by the bacterium Helicobacter pylori. It was not easy persuading the scientific community to accept the new model.
Barry Marshall, an Australian scientist with a flair for theatrics, resorted to swallowing a beaker of the bacteria to help settle the question. Today, ulcers are treated primarily with antibiotics instead of acid-blocking drugs.
Infectious-disease specialists now are turning attention to coronary artery disease, which is caused by a progressive buildup of fatty deposits inside vessels that feed the heart. Scientists have long known that diabetes, high blood pressure, tobacco use and a family history of the disease increase a person's odds of artery disease and the risk of a subsequent heart attack or stroke. But those factors account for only about half the incidence.
In 1997, Boston researchers showed that men with higher levels of a certain protein circulating in their blood over a period of years had an increased risk of eventually suffering a heart attack or stroke. The protein is a well-known sign of inflammation, which can indicate a bacterial infection.
Separately, Joseph Muhlestein of the LDS Hospital in Salt Lake City and his colleagues discovered that a peculiar bacterium, Chlamydia pneumoniae, often can be found inside blood vessel cells of people with heart disease - but not generally in the cells of healthy people.
C. pneumoniae - a close cousin of C. trachomatis, which causes a common sexually transmitted disease - is best known as a cause of pneumonia and bronchitis. It is unlike most other bacteria because it lives not on cells but inside them, much as a virus does.
It is possible that the microbe is an innocent bystander, a bacterium that feels at home in arteries damaged by years of fat consumption and a lack of exercise. But rabbits on fatty diets develop hardening of the arteries much faster when they are infected with C. pneumoniae, suggesting that the microbes actively contribute to the disease.

Is Heart Disease Caused by Germs? Microbes Linked to More Illnesses

By Rick Weiss Washington Post Staff Writer Monday, March 1, 1999; Page A01

From gallstones to arthritis to heart disease, many illnesses long presumed to have roots in genes or lifestyle may be caused largely by infectious agents, a growing number of scientists believe. That prospect is raising the intriguing possibility that people can "catch" kidney stones, cerebral palsy or Alzheimer's disease.
Most of the evidence remains circumstantial. A microbe may be suspiciously present in people who have a disease, for example, and not in those who don't -- suggesting, but not proving, causality.
But for some conditions -- including heart disease, the nation's top killer -- many scientists feel certain that microbes play at least a contributing role where none was suspected previously. Last week, researchers announced that they had discovered a molecular mechanism by which mice can get heart disease from a bacterium. And high-tech tests have been picking up previously undetectable bacterial "fingerprints" in people with other chronic conditions, strengthening the case that microbes are the hidden perpetrators in those diseases as well.
The implications of the new theory are enormous, researchers say. Most important, it suggests that vaccines or antibiotics may have an unexpectedly big role to play in the treatment of chronic diseases that today are treated with only modest success through lifestyle changes, such as exercise and improved diet.
"If an infectious agent is responsible for even a portion of these diseases, that could change the outlook for treatment and prevention dramatically," said Barry Bloom, dean of the Harvard School of Public Health. "I see chronic disease as the next frontier for vaccines."
Bloom and others cautioned against placing too much blame on bacteria. For most chronic diseases, they are probably just part of the puzzle, they said. And the prospect of widespread, long-term use of powerful antibiotics carries its own problems, including the possible emergence of drug-resistant "superbugs." Attractive though the idea may be, a pill or shot will not likely allow people to ignore everything they have learned about how to remain healthy into old age.
"The bacteria by themselves are not going to give us the only useful answers," said Janice Kiecolt-Glaser of Ohio State University, who studies the effects of stress on health. "You could have the bug, and if resistance is altered by stress or other factors, you could be more prone to not healing or to the infection progressing."
Nonetheless, said Anne Schuchat, chief of the respiratory diseases branch at the Centers for Disease Control and Prevention (CDC) in Atlanta, chronic conditions such as heart disease take such a big toll on society that even a modest contribution by bacteria deserves to be targeted. "Even if there are still a lot of questions," she said, "it's really worth a lot of attention."
The revolution began about five years ago, when definitive evidence arose that stomach ulcers are caused not by excess stomach acid, as had long been presumed, but by the bacterium Helicobacter pylori.
It wasn't easy persuading the scientific community to accept the new model. Barry Marshall, an Australian scientist with a flair for theatrics, resorted to swallowing a beaker of the bacteria to help settle the question. Today, ulcers are treated primarily with antibiotics instead of acid-blocking drugs.
Infectious disease specialists now are turning their attention to coronary artery disease, which is caused by a progressive buildup of fatty deposits inside vessels that feed the heart. Scientists have long known that diabetes, high blood pressure, tobacco use and a family history of the disease increase a person's odds of artery disease and the risk of a subsequent heart attack or stroke. But those factors account for only about half the incidence of this disease.
Several lines of research support the proposition that a microbe might cause coronary artery disease. In 1997, Boston researchers showed that men with higher levels of a certain protein circulating in their blood over a period of years had an increased risk of eventually suffering a heart attack or stroke. The protein is a well-known sign of inflammation, which can indicate a bacterial infection.
Separately, Joseph B. Muhlestein of the LDS Hospital in Salt Lake City and his colleagues discovered that a peculiar bacterium, Chlamydia pneumoniae, often can be found inside blood vessel cells of people with heart disease -- but not generally in the cells of healthy people.
C. pneumoniae -- a close cousin of C. trachomatis, which causes a common sexually transmitted disease -- is best known as a cause of pneumonia and bronchitis. It is unlike most other bacteria because it lives not on cells but inside them, much as a virus does.
It is possible that the microbe is just an innocent bystander -- a bacterium that feels at home in arteries damaged by years of hamburger consumption and a lack of exercise. But rabbits on fatty diets develop hardening of the arteries much faster when they are infected with C. pneumoniae, suggesting that the microbes actively contribute to the disease.
A study published in the journal Science last Friday offered the best evidence yet for precisely how chlamydia may cause heart disease. A protein found on chlamydia, it turns out, is almost identical to one found in heart tissue in mammals. Scientists discovered that when a mouse's immune system attacks the bug, it accidentally attacks the heart protein, too. The resulting syndrome is not exactly the same as human heart disease, said Josef M. Penninger, the University of Toronto immunologist who led the study. But the similarities have convinced him that something very much like this may be causing heart disease in people.
If Penninger is right, then heart disease might be prevented or even reversed by a drug that tempered the immune system's reaction to chlamydia. Scientists trying to create a vaccine against chlamydia would face a challenge, however. Vaccines work by stimulating the immune system and could inadvertently trigger the immune response that causes heart disease.
If the microbe, and not the immune response against it, causes heart disease directly then antibiotics might prove useful. Two studies in people have indicated that a short course of antibiotics known to kill chlamydia can reduce the risk of a heart attack or stroke for up to 18 months. Another study was unable to verify the benefit and other studies are ongoing.
Heart disease is not the only chronic disease in which C. pneumoniae may play a role. Neuroscientist Brian Balin of the Philadelphia College of Osteopathic Medicine and his colleagues have found signs of the microbe in 27 of 29 autopsied brains of people with Alzheimer's disease, but in only one of 19 brains from non-Alzheimer's patients.
The bacteria, found in so-called glial cells that surround neurons, may be "opportunists" taking advantage of dying brains, Balin said. But studies indicate that they can cause Alzheimer-like damage. "I think it's definitely an agent that has to be considered as a potential causative or at least a risk factor for Alzheimer's disease," he said.
Gallstones and kidney stones recently have been added to the list of diseases that might have microbiological roots. Studies led by Phillip B. Hylemon of the Medical College of Virginia in Richmond, for example, showed that gallstone patients have 100- to 1,000-fold higher levels of Clostridia and eubacteria in their intestines. Those bacteria generate deoxycholic acid, which prompts the liver to secrete bile especially rich in cholesterol -- a key risk factor for gallstone formation. In one encouraging finding, antibiotics have been shown to lower the concentration of these bacteria in people and decrease bile levels to below the threshold needed to make gallstones.
Last summer, Finnish researchers reported provocative evidence that "nanobacteria" -- smaller than many viruses -- may be a cause of kidney stones. Using genetic fingerprinting tests and other methods, they found that the bacteria can build a mineralized coating around themselves, upon which additional proteins and minerals can accumulate. In one study of 30 kidney stones, all had traces of nanobacteria in their cores. DNA studies suggest that the nanobacteria are related to a small, slow-growing, rod-shaped bacteria known to cause abortions in animals and blood poisoning in people.
Juvenile rheumatoid arthritis, generally considered an immune system disorder, also may be caused by a microbe, although the evidence remains indirect. The proposed culprit is Mycoplasma pneumoniae, a common cause of "atypical pneumonia" in people. In a 17-year Canadian study, diagnoses of the disease peaked in the same years as M. pneumoniae infections did.
Some researchers suspect that scleroderma, a painful chronic disease affecting connective tissues under the skin, also may be caused by mycoplasma. A recent U.S. study found a virtually complete disappearance of symptoms in four of six patients treated for one year with an anti-mycoplasma antibiotic called minocycline.
Cerebral palsy, too, may prove to be infectious. That disease, which affects about 500,000 Americans and is characterized by brain damage at birth, was long believed to have been caused by oxygen deprivation before or during birth. But a study last year suggested that infected amniotic fluid may often be to blame.
Researchers have not isolated a particular microbe from newborns with cerebral palsy. But a technique being studied by David Relman at Stanford University may help scientists find the cause of that and other diseases for which there is evidence of infection but no isolated microbe. Relman is using DNA fingerprinting methods to find tiny fragments of microbial DNA in cells of people with various diseases.
Some scientists suspect that such tests will reveal infectious causes for more and more chronic diseases. "They will pop up in all kinds of places," the University of Toronto's Penninger said.
Attractive as the emerging evidence is, not everyone is so sure. To a microbiologist, the world can sometimes seem full of "infectious agents in search of a disease," said Schuchat of the CDC. "How much is real and how much is a fad remains to be seen."
Infections at Fault?
Infections could be at the root of a variety of diseases, including the following:
     Suspect microbe
Heart disease
     Chlamydia pneumoniae, cytomegalovirus
Alzheimer's disease
     Chlamydia pneumoniae
Juvenile rheumatoid arthritis
     Mycoplasma pneumoniae
     Mycoplasma species
Temporomandibular joint dysfunction
     Chlamydia trachomatis
     Gram-positive anaerobic bacteria
Cerebral palsy
Kidney stones
     Brucella-like "nanobacteria"
© Copyright 1999 The Washington Post Company

Common gastrointestinal problems can be a real pain Nutrition

By Craig T. Hunt - The Spokesman-Review
December 2, 1998

Spokane _ At one time or another, everyone has a tummy ache or a bout of diarrhea. You probably don't think much about how your eating habits affect your digestive tract, yet millions of people must pay extra attention to that 30 feet of tubing inside them.

Gastrointestinal problems are the most common medical complaint after the common cold. Some are life-threatening, others are far less formidable.

Have you ever listened to another person's stomach area? You hear gurgling and creaks that sometimes sounds like sea creatures talking to each other.

Some gastrointestinal diseases sound odd, too, with names like celiac sprue, Crohn's disease, ulcerative colitis and diverticulosis.

Celiac sprue, an inherited disorder, affects an estimated one in 2,500 people. They cannot tolerate even tiny amounts of wheat, oats, rye, barley, buckwheat, bulgur, quinoa, amaranth or millet. A protein portion in these grains, called gliadin, damages the lining of the small intestine, causing chronic diarrhea, abdominal cramping and bloating.

Eventually, the absorptive structures of the intestine, called villi, become damaged. Absorption of almost all vitamins and minerals is affected, leading to such problems as fatigue, growth failure, night blindness, muscle cramps, osteoporosis and decreased ability of the blood to clot. Itchy blisters may form on the skin, especially the knees, elbows and feet.

Incredibly, all of these symptoms will disappear with the complete avoidance of gliadin-containing grains. Unfortunately, gliadin is added to tens of thousands of food products including vinegar, salad dressings, soups, cereals, cheese sauces, meat bastes, bouillon and food dyes. Even licking a stamp can cause a reaction, because the glue contains wheat starch.

There's a celiac support group in Spokane called the Celiac Explorers Group; contact Melba Tschirley at 922-4366. The Seattle-based Gluten Intolerance Group of North America can be reached at (206) 325-6980.

Like celiac sprue, Crohn's disease is inherited, but the cause is more elusive -- possibly a virus or bacteria interacting with the body's immune system. Certain foods, depending on the person, can also trigger symptoms: inflammation, abdominal pain, diarrhea, fever, weight loss and joint pain. As with celiac, the intestinal villi become less functional and valuable nutrients are not absorbed.

Ulcerative colitis is a similar form of inflammatory bowel disease in which the sensitive mucous layers of the intestines become ulcerated and bleed.

If untreated, celiac sprue, Crohn's and ulcerative colitis all can damage the digestive tract to the point where diseased sections need to be removed, which further reduces absorption of nutrients.

The treatment for Crohn's and ulcerative colitis includes avoiding foods the body doesn't tolerate well, frequent feedings of high-calorie, high-protein foods and an increase in fiber, unless the intestines are inflamed. Vitamin and mineral supplements are also necessary, and omega-3 fatty acids from fish oil can help reduce inflammation.

Diverticulosis and diverticulitis, its more advanced form, begin with herniations of the intestinal mucous membrane, often because of lack of fiber in the diet. When waste matter collects in the herniated pockets -- again, a result of not eating enough fiber to scrub the system -- infection and inflammation cause ulceration and perforation. Symptoms can include abdominal pain and rectal bleeding.

An increase in fluids and dietary fiber are both the best defense and the best cure. Eating at least two teaspoons of wheat, barley or rice bran daily and drinking plenty of water (at least eight cups) is helpful for prevention. Psyllium seed in the form of Metamucil can also be helpful, if you can tolerate it, but nuts and seeds must be avoided in the diet because they can become trapped in the intestinal pockets.

One of the most common digestive disorders, irritable bowel syndrome, affects 20 to 30 percent of the population at some point in their lives.

The cause of irritable bowel syndrome is unknown, although stress seems to play a large part. Symptoms include painless diarrhea alternating with constipation over a period of at least three months. Excess caffeine, laxatives, antibiotics and decreased fluid intake can make symptoms worse.

Remedies include exercise, relaxation techniques and massaging the abdomen in a clockwise manner -- left to right -- which is the direction food moves through the body.

Short-term diarrhea is another common intestinal problem. Drinking bouillon and fruit juice can help replace lost electrolytes. A peeled apple, or unsweetened applesauce, can sometimes help. Low-fiber foods, like white bread, followed by a protein (meat or cheese) can also be effective in slowing diarrhea.

The bottom line in preventing or dealing with a gastrointestinal disease is to know what foods your body does and doesn't tolerate well. A high-fiber diet (25 to 35 grams daily) can help keep the colon functioning properly; fruits, vegetables and whole grains are your best sources of fiber. But there are times when low-fiber foods are more advisable, especially during times of inflammation.

If you are having symptoms of any of the above-mentioned diseases, be sure to discuss it with your doctor. We're all a little shy when it comes to talking about our bowels, but with 30 feet of tubing in us, it's sometimes hard to ignore when it's complaining.

*Craig T. Hunt, a registered dietitian and nutritionist in private practice in Spokane, writes about nutrition each month for IN Food.

This article is placed at:

Does diet work?
Sunday June 15, 12:43 GMT

There is no clear or final answer to this question, but if you run through this copy of the web page Crohn's Disease - Nutritional Therapy References (which someone sent to me by email) you will get some kind of an idea.

Date: Mon, 10 Aug 1998 12:02:58 -0400
From: Midas Gold <>
Subject: A Gut Feeling

For anyone who's interested, here is an IBD/gut bacteria thesis that
draws stikingly different dietary conclusions than does Elaine
Gottschall in _Breaking the Vicious Cycle_.

"A Gut Feeling

"If you thought junk food would merely make you fat, think again. You
could also be fattening a hungry mass of alien gut bacteria that may
repay you with bowel disease or even cancer.

"Gail Vines reports

"WHAT'S the difference between the contents of your bowels and the
noxious black sludge at the bottom of an estuary? Not a lot
perhaps--particularly if you live on a diet of junk food. The same
sulphur loving bacteria that give mud in estuaries and ocean sediments
their pungent, rotten-egg smell may have invaded your gut. In the sea,
they are notorious troublemakers with a penchant for corroding oil
pipelines, and their effect on human passageways may be equally

"All these microbes need to flourish in your guts is a good supply of
sulphurous compounds. And that's where your diet comes in. Eat large
amounts of animal protein and processed food and you could be giving
these bad bugs everything they need to triumph at the expense of your
natural healthy gut microbes. Over the past decade, the researchers
doing this work have steadily accumulated evidence to implicate
sulphur bacteria in a range of human diseases from inflammatory bowel
diseases to colon cancer.

"'It's a potential bombshell,' says John Cummings, head of the 'gut
group'--the team pioneering this type of work at the Dunn Nutrition
Unit at Addenbrooke's Hospital in Cambridge. Sulphur-based
preservatives are in most processed foods, from instant potato to jams
and dried fruit, as well as in most wines, beers and ciders. Sulphur
compounds are one of the world's oldest food additives, used by the
ancient Greeks and Egyptians to preserve wine, and widely regarded as
both versatile and safe. So if these foods do encourage the growth of
alien microbes that are linked to disease, the food and drinks
industry could face a crisis to rival salmonella or BSE.

"The story involves a series of coincidences and begins 500 kilometres
north of Cambridge, in the port of Dundee on the east coast of
Scotland. There, in the mid-1980s, two PhD students from Dundee
University, Glenn Gibson and George Macfarlane, were studying the
ecology of the Tay estuary. 'As it happens, the results weren't
particularly exciting,' chuckles Gibson. But the young researchers did
learn a lot about sulphur bacteria--knowledge that was to prove useful
in a very different quarter.

"These mud-loving organisms, officially known as sulphate-reducing
bacteria, find plenty to feast on in the oxygen-free (anaerobic) sea
sediments. That's because they can exploit both the hydrogen that
comes from the fermentation of countless microbes in the stagnant mud,
and the plentiful sulphate in seawater. The bugs make their own energy
from these raw ingredients, converting sulphate to sulphite and then
creating a poisonous waste product: hydrogen sulphide, with its
telltale smell of rotten eggs. To humans, the compound is as toxic as
cyanide. In water, it rapidly becomes highly corrosive sulphuric acid.

"In the late 1980s the oil industry was well aware how caustic
by-products of the sulphur-loving organisms could wreck their
pipework, but no one yet imagined that they could also be causing
trouble in the human gut. This idea was to emerge from
multidisciplinary teamwork as Macfarlane and Gibson moved south to
Cambridge, to join Cummings and his gut group. The timing was good for
the two young microbiologists. 'Researchers were discovering just how
important the gut bacteria are in health and disease,' says Cummings.
His own team's decision to pursue this line of enquiry was to lead
them eventually to finger the sulphur lovers as the agents of disease.

"Something in the Wind

"The quest began in an unlikely place--with the gases made by gut
bacteria that people give off when they belch or fart. The team
devised an elegant technique to provide the first accurate
measurements of the composition of intestinal gas in healthy people.
For 36 hours, volunteers lived in a small airtight room, while
researchers controlled the flow of air through it. By measuring the
difference in the concentration of gases in the air entering and
leaving the room, the investigators could determine which gases were
coming from volunteers.

"The results, published in 1992, were a surprise. Everyone knew that
gut bacteria churn out a variable mix of odourless, mainly harmless
gases--hydrogen, nitrogen, carbon dioxide and methane. But the team
was surprised by how little hydrogen they found in the air leaving the
room--given the chemical composition of the foods the volunteers had
eaten. Something in the gut was gobbling up much of the available
hydrogen. Another finding was puzzling too: some people produced
substantial amounts of methane, while others produced much less, or
none at all.

"The methane could have come from only one source: methane-producing
bacteria, otherwise known as methanogens. These bacteria consume
hydrogen, which would explain the low levels of this gas given off by
people harbouring methanogens. But breath tests designed to detect
methane suggest that only about half of the people living in North
America and Northern Europe have methanogens living in their gut. Why
do some people have them, while others do not? And what is soaking up
the hydrogen if methanogens aren't?

"Sulphate-reducing bacteria, first reported in the human gut in the
late 1970s, looked like good contenders. Gibson and Macfarlane,
recalling their experiences in the Tay estuary, quickly realised that
this was not such a preposterous idea. After all, microbial
fermentation in the final part of the gut, the distal colon, provides
anaerobic conditions on a par with those in marine muds. And
sulphate-reducing bacteria predominate in marine sediments where they
use up hydrogen as well as sulphurous compounds. What's more, on the
seabed these microbes get the better of methane-generating bacteria if
sulphate is present.

"High levels of sulphur are also present in the typical Western diet.
Could sulphate-reducing bacteria be displacing methanogens inside the
guts of people who eat large quantities of meat, packed with
sulphur-rich amino acids, and processed foods and fermented drinks
preserved with the ubiquitous sulphur-based food additives?

"Fighting Back

"To test this idea the team asked volunteers who normally produce
methane in their breath to eat a diet rich in sulphate. Ten days on,
the breath of half of their subjects no longer showed significant
traces of methane. By day 15, sulphide levels in their faeces had shot
up. When they stopped eating the added sulphate methanogens returned
while the sulphate-reducing bacteria went into sharp decline. In
another study, the Dunn team found that rural South Africans, eating a
diet low in sulphur, were virtually all methane-producers.

"Intrigued, the Dunn researchers next began to wonder if these gut
microbes affected human health. They compared the levels of
sulphate-reducing bacteria in the faeces of healthy people and in
patients suffering from ulcerative colitis, a serious inflammatory
bowel disease that afflicts up to one in a thousand people in Britain
and the US. Work done in the US during the 1970s showed that
'germ-free' lab animals lacking any gut bacteria do not develop
colitis-like symptoms, even when exposed to irritants such as
sulphated seaweed. Bacteria in general had been implicated in the
disease, but could the sulphate reducers be major players?

"The team's results were striking. Virtually everyone with colitis--96
per cent of the sufferers tested--played host to the sulphate lovers,
but only 50 per cent of the healthy people did. In particular, the gut
of someone with colitis was home to large numbers of sulphate-reducing
bacteria from the genus Desulfovibrio. 'There turned out to be more
subtypes of these bacteria in the human gut than we had expected, with
some more active or virulent than others,' says Cummings. One strain
isolated from the colons of people with colitis showed signs of being
adapted to life in an inflamed gut, Gibson found. Growing in a
continuous culture 'gut model' fermenter in the laboratory, the strain
can survive high flushing rates that simulate diarrhoea in the colon.

"Nevertheless, not everyone harbouring the sulphate-reducing bacteria
was ill. And some ill people did not have the bacteria. So, what
exactly is their link with colitis? Do they cause it, exacerbate it,
or simply take up residence in a diseased colon because they can?
Macfarlane points out that pinpointing an individual cause of
ulcerative colitis is virtually impossible because it is a chronic
inflammatory condition intimately involved with the body's immune
response. 'It may be that sulphate-reducing bacteria contribute to the
maintenance of the disease rather than kick it off,' he cautions. 'It
is difficult to tie gut disease to a particular organism,' adds
Gibson. The gut is home to at least 400 species of microbes, many of
which are difficult or impossible to grow in lab cultures--and the
vast majority of which are harmless.

"Gibson, who is now at the Institute of Food Research in Reading, is
investigating why some sulphate-reducing bacteria are linked to bowel
disease but others are not. By studying mutant strains genetically
engineered not to make hydrogen sulphide, he hopes to find out whether
it is the bacterial invasion of gut cells alone that causes damage, or
whether the sulphide by-products are to blame, or indeed both. Gibson
hopes this will reveal how sulphate-reducing bacteria can cause

"Defective Cells

Meanwhile, an Australian abdominal surgeon has already found one way
in which sulphide might damage the gut. In the 1980s Bill Roediger, at
the Queen Elizabeth Hospital in Woodville, near Adelaide, first
noticed that, in people with ulcerative colitis, the epithelial cells
that line their colons don't function normally. These cells lack the
ability to oxidise a vital fatty acid called butyrate, which is
normally their main nutrient. This metabolic abnormality could be the
first step in the development of the disease: it seems to precede the
start of obvious colitic changes in the colon. Significantly, in 1993,
he showed that exposure to sulphides selectively inhibits the ability
of colon cells to use butyrate.

"More work is needed to understand the link between diet, bacteria and
disease, says Macfarlane. Such research could tell us how to encourage
beneficial bacteria and freeze out the harmful ones. One day there
might even be a vaccine against harmful gut organisms. But at the
moment, the most hopeful strategy is to encourage a process of
'natural displacement' through changing what we eat.

"Meat and other foods high in protein release sulphur-amino acids as
they are digested. Cummings's team believes these feed bacteria in the
same way that other sulphur compounds do. A preliminary study at the
Dunn shows that as meat consumption rises from 60 to 600 grams per
day sulphates in the urine double, and sulphides in faeces increase
tenfold. A diet rich in meat has long been implicated in colon cancer,
and Cummings suspects that the toxic sulphides released by these
microbes might promote cancerous changes in gut cells by damaging
their DNA.

"But what about vegetarians? Are they off the hook? Vegetable
protein--notably in beans and seeds--also contains amino acids with
sulphur groups attached, so why are vegetarians at lower risk of colon
cancer? The crucial difference could be in the balance of nutrients.
In plant foods, protein comes in carbohydrate-rich packages. Cummings
suspects that this combination could make the sulphur-amino acids
harmless. Carbohydrate fuels the growth of beneficial bacteria which
snap up the sulphur amino-acids to incorporate into their own
proteins. The end result isn't harmful sulphide, but lots of
beneficial 'biomass'--bacterial bulk that helps to speed the passage
of faeces through the gut. It is possible, he says, that carnivores
who eat lots of plant foods and carbohydrates along with their meat
could be protected too.

"The second major source of sulphur in our diet is a large family of
sulphur additives in foods and drinks: sulphur dioxide, sulphites,
bisulphites, metabisulphites and sulphates, known in Europe by E
number codes E220 to E227, but often collectively called 'sulphur
dioxide'. These sulphur compounds are the major preservative in the
Western diet. 'They are in hundreds and hundreds of foods,' says
Cummings, everything from sausages and burgers to jam, dried raisins
and instant soup. Even fresh foods may not be sulphur-free--packaged
salads are 'gassed' with sulphur dioxide to prolong their shelf life.
Soft drinks, wines, beers and ciders can contain widely varying
levels, which do not have to be listed on the label. It is detoxified
by enzymes in the liver and kidneys which makes sulphur dioxide 'a
very safe additive--about the safest thing we've got that does that
job', says Bronik Wedzicha, professor of food science at the
University of Leeds. Nonetheless, a shadow of doubt has already been
cast on this venerable preservative. Especially lavish use--in
American salad bars, for instance--has now been curtailed, after
allergic reactions particularly in people with asthma.

"Although sulphur additives are in such a huge variety of foods, no
one has yet systematically monitored the amount ingested with an
average Western diet. In Britain, the Ministry of Agriculture
Fisheries and Food recognises an acceptable daily intake for
sulphur-based preservatives. But if you eat large amounts of processed
food, washed down with beer or wine, your daily consumption could be
well above this level. So, with funding from MAFF, Cummings and his
colleagues are assessing how much sulphur people typically consume, by
measuring their dietary intake and monitoring the amount of sulphate
excreted in urine. 'The aim is to discover how much sulphur we are
getting from protein and how much from sulphur additives,' says

"Although the evidence is not yet in, Cummings suspects that other
inflammatory bowel diseases, such as Crohn's disease, as well as the
ill-defined irritable bowel syndrome, could also be linked to
sulphate-reducing bacteria. If a link between Desulfovibrio bacteria,
gut disease and a dietary source of sulphur can be tied down and the
mechanism identified, it will mark a major turning point in the way we
think about human health. As bacterial warfare is waged in the human
gut, our health may yet depend on feeding an army of friendly microbes
and starving the foe into submission."


This should be of interest to those of you with CD?

Antibody Treatment For Crohn's Disease

Monday February 24 5:51 PM EST
NEW YORK (Reuters)
-- Crohn's disease is a chronic inflammation of the intestines that causes episodes of diarrhea, abdominal pain, fever, and fatigue. Now, a new study suggests that using an antibody to block tumor necrosis factor -- an immune system protein -- may provide some relief for Crohn's disease sufferers.

Currently, these patients have to rely on steroids and strong immunosuppressing drugs to prevent destruction of their digestive tract. However, more study is needed to determine if the new method can successfully relieve symptoms for a period of time longer than a few weeks.

The blocking agent is an antibody called CDP571, which has the ability to neutralize tumor necrosis factor-alpha (TNFa) -- a molecule thought to play a key role in the disease, according to a report in The Lancet. Over a two-week period, an injection of CDP571 in 21 patients reduced the median disease activity index -- a measure of symptoms and blood inflammatory factors -- from 263 to 167.

Overall, nine patients were considered to be in or near remission, which is a disease activity score of less than 156. The patients did have some side effects during infusion of the antibody, including dizziness, abdominal pain and gas.

Another 10 patients given an injection of a placebo, or inactive drug, had a drop from 253 to 247 -- a statistically insignificant difference, according to lead study author, Dr. William Stack, of the Department of Gastroenterology at University Hospital in Nottingham, U.K.

"These data suggest that antibody neutralization of TNFa is a potentially effective strategy in the management of Crohn's disease," wrote Stack. However, "the use of CDP571 in
Crohn's disease requires further study."

But there was no evidence that the beneficial effects persisted after the antibody was cleared from the body, the authors noted. And, as with any antibody treatment, there are concerns that it may lose effectiveness when given repeatedly.

Most engineered antibodies are made in mice, but rodent proteins are recognized as foreign by the human immune system. Although an antibody may be successful at first, the body could rapidly destroy subsequent exposure to mouse antibodies.

CDP571 was produced in rodents, but genetically engineered to contain almost all human proteins -- and is, therefore, less likely to be destroyed. Altogether, the antibody is 95% human and 5% mouse.

"Further studies are underway to define an optimum dose of CDP571 in Crohn's disease, and to investigate the efficacy of repeated dosing," the authors concluded.

SOURCE: The Lancet (1997;349:521-524)

UC News: Nicotine
Sun, 2 Mar 1997 11:22:46 GMT

The following article was printed in our newspaper this morning:

Researchers writing in the March 1 issue of the Annals of Internal Medicene say people suffering from moderate UC can significantly iumprove their respective conditions by wearing a nicotine skin patch and having a dring or two a day.

The nicotine study was carried out by doctors under the direction of Dr. William Sandborn at eh Mayo Clinic.

They go on to say that they gave the group a nicotine patch that had 22 milligrams a day and it was a 4 week trial.

Doctors found that 39% of those receiving nicotine reported significant improvement of their symptoms - improvements that were confirmed with lab tests and physician exans.

There was more but I don't this message to be too long. I have been on the diet 9mo and found out this week that the Pecan Flour is a big NO NO for me. I was doing fine until the big "D" hit after eating the flour.

Take care out there
Bob Chisam

Nicotine - new information
Sun, 2 Mar 1997 15:45:03 GMT
From: (Johnson, Terri Ristau)

Re: Jim Prousalis's info here is that article and another that once again speaks of the benefits of nicotine (patch). These are from the San Diego Union Tribune March 1,97. I will also include some of the more recent news from the Colitis Crohns Foundation of America's homepage regarding nicotine and oral tolerance

Dave Johnson


(Page C-1 )

Isis drug fights off Crohn's disease
Test results are called dramatic

By Craig D. Rose, STAFF WRITER

01-Mar-1997 Saturday

Isis Pharmaceuticals yesterday announced strongly positive results from an
interim test of its drug for Crohn's disease, a chronic gastrointestinal
disorder for which there often is no effective treatment.

In a study involving 20 patients, Isis said 47 percent of those treated
with its drug experienced complete remission, compared with no remissions
among patients who received a placebo.

The group treated with Isis 2302 also had significantly lower requirements
for steroids than placebo patients. Steroids are used to control symptoms,
but they can cause serious side effects of their own, including

Isis said it will proceed with Boehringer Ingelheim, its development
partner, in a third phase of testing with about 300 patients.

The larger study is designed to provide a definitive assessment of the
effectiveness of Isis 2302. The test is expected to be completed within 24

An industry analyst, meanwhile, said results announced yesterday were
particularly impressive.

"Very rarely in a phase two study do you get results that are this
dramatic," said James McCamant, editor of the Medical Technology Stock
Letter in Berkeley. "Based on these results, the probability that the drug
will prove to work in a phase three is well over 90 percent."

The strength of the results from the interim study also surprised Isis.

"We never expected to obtain statistically significant results from this
trial," said Dr. Stanley Crooke, chief executive officer of the Carlsbad
company. "Five patients were weaned completely from steroids and these are
patients who had taken the drugs for years."

He said the company is particularly encouraged because the Isis treatment,
which was administered over one month, continued to be effective for as
long as six months in many patients.

"One patient, a year out from the treatment, remains off steroids and feels
well," Crooke said.

Crohn's disease affects about 200,000 people in the United States and an
equal number in Europe. The disease causes an array of symptoms including
abdominal pain, diarrhea, anemia and fistulas, which are abnormal passages
from the digestive system to the skin or other organs.

Isis shares yesterday closed at $19.375, up 50 cents in heavy trading on
the Nasdaq Stock Exchange. During the previous session, as advance notice
of results from the Crohn's disease test began to spread, the company's
shares closed up 25 cents.

The test results were hailed as the strongest support yet for Isis'
strategy for drug development, which focuses on what is called anti-sense
technology. The approach seeks to combat disease at the cellular level.

Crooke said the Crohn's disease treatment data provided a signal moment for
anti-sense technology, marking the first time it had demonstrated
effectiveness when administered systemically.

Isis, which employs about 300 people, also announced positive interim
results for an anti-sense treatment it is developing for the blindness
associated with AIDS.


(Page A-14 )

Some benefits seen in alcohol, nicotine
May help with colitis, angina, studies suggest


01-Mar-1997 Saturday

Alcohol and nicotine may not always be bad for you, despite all the
evidence to the contrary, two new studies published today suggest.

While the doctors don't advocate retiring to the nearest smoke-filled bar,
researchers writing in the March 1 issue of the Annals of Internal Medicine
say people suffering from moderate ulcerative colitis and men seeking to
avoid heart disease can significantly improve their respective conditions
by wearing a nicotine skin patch and having a drink or two a day.

The nicotine study was carried out by doctors under direction of Dr.
William Sandborn at the Mayo Clinic on 64 nonsmoking patients. They were
divided into a group that got the maximum dosage of nicotine patch that's
generally tolerated, 22 milligrams a day, and a control group that wore
unmedicated patches.

All had mild to moderate ulcerative colitis that conventional medication
was failing to control, though they continued to take the medicine during
the four-week trial.

Doctors found that 39 percent of those getting nicotine reported
significant improvement of their symptoms. The improvements were confirmed
with laboratory tests and physician examinations. Improvement also was
noted in 9 percent of those getting the placebo.

The results mirror two earlier studies that also used very high doses of
nicotine on a 16- to 24-hour cycle to achieve remission for roughly 30
percent to 50 percent of patients. Other previous studies using lower doses
of nicotine showed much less success.

Nicotine is disparaged as addictive to smokers, but researchers have found
evidence of positive effects from nicotine on several illnesses, including
Alzheimer's disease and schizophrenia.

All the research on colitis builds on findings published more than a decade
ago that almost everyone suffering from ulcerative colitis is a nonsmoker,
while conversely, smoking increases the risk of contracting a similar
inflammatory bowel disorder, Crohn's disease, almost five-fold.

The researchers suggested that more studies need to be done to see whether
longer duration of treatment might result in reversal of the illness.

In the heart-alcohol study, researchers led by Dr. Carlos Camargo Jr. at
Brigham and Women's Hospital and several other Boston institutions tracked
the incidence of angina and heart attack among 22,000 male physicians
taking part in a national study of heart disease over time.

Compared with men who had less than one drink a week, those who consumed
two or more drinks a day had a 56 percent lower risk for angina (chest
pains from a reduced supply of oxygen to the heart during exertion) and a
47 percent lower risk for heart attack.


(Page A-14 )


Nicotine therapy may help ease the symptoms of active ulcerative colitis,
according to recent studies headed by William Sandborn, M.D. (Mayo Clinic, Rochester, Minn.)

The first Mayo Clinic studies involving nicotine, conducted earlier this year,
entailed the use of a patch. Nearly 39% of persons treated with the patch showed
significant improvement; however, side effects such as skin rashes, nausea,and
dizziness were common. To prevent large amounts of nicotine from entering
the blood stream and causing these adverse effects, researchers developed nicotine enemas,
which deliver the drug directly to the colon.

Two different types of nicotine enemas were studied: one group of patients was
treated solely with nicotine, while another was treated with a combination of
nicotine and carbomer, an acrylic acid polymer. Carbomer, which coats the
wall of the gut, slowly releases nicotine into the colon. Because the bowel absorbs
smaller quantities of the drug, adverse effects should be lessened. Nearly 75% of
patients treated with the nicotine/carbomer enema showed significant improvement in their
condition, with minimal side effects. The results of the study involving
nicotine only are not yet available.

These positive results prompted Medeva PLC, a London-based drug company, to
purchase the rights to this experimental therapy. Under terms of the agreement, the Mayo
Clinic will continue to study nicotine's effectiveness and safety as a
treatment for colitis. (For example, though results so far have been promising, it is also
important to demonstrate that long-term use of nicotine therapy will not be
addictive or produce other adverse effects associated with smoking.) In addition,
studies of an oral nicotine capsule are expected to begin in the first half of 1997.

CCFA will continue to report on this potential therapy as new study results
become available.



Several recent clinical trials have studied the efffectiveness
of an experimental therapy, known as oral tolerance, in
treating such illnesses as multiple sclerosis, rheumatoid
arthritis, and uveitis (inflammation of the eye). The results
have been encouraging, and this treatment is being considered
for other diseases which, researchers suspect, may be
autoimmune disorders. Unlike corticosteroid and
immunomodulators, which are currently used to treat such
disorders, oral tolerance therapy does not appear to have
potentially serious side effects. It may one day offer hope to
people who have inflammatory bowel disease (IBD).

Autoimmunity means that inflammatory cells (e.g., white blood
cells, such as T cells), which normally defend the body against
antigens (bacteria, viruses, etc.) are unable to distinguish
between foreign substances and the body's own tissue. As a
result, the inflammatory cells attack healthy tissue, causing
chronic inflammation.

These self-destructive immune responses may occur in such
tissues as the joint surfaces (rheumatoid arthritis), the
thyroid gland (Grave's disease), the central nervous system
(multiple sclerosis), and the intestine (IBD). In each case,
the inflammatory cells target specific proteins, which are
normally found in the tissues of these organs. Such proteins
are, therefore, known as "self-antigens" or "autoantigens."

What is Oral Tolerance Therapy?

By feeding patients an oral preparation containing the
autoantigens that play a role in their disease, it may be
possible to inhibit the immune response. Simply put, the body's
ability to tolerate these proteins is restored, a phenomenon
known as oral tolerance.

Though scientists have long been familiar with this concept,
they still do not know exactly which immune mechanisms generate
the state of oral tolerance. Current theory suggests that T
cells migrate from the intestine to other tissues, where they
diminish the immune response. A recent series of studies
provides an alternate hypothesis: that high doses of oral
antigens completely inactivate specific T cells. As studies
provide new data, researchers will attempt to learn how to
generate and maintain oral tolerance in various diseases that
have autoimmune characteristics.

Studies In Animal Models and Humans

Studies in animal models of such illnesses as diabetes,
uveitis, and multiple sclerosis have shown that oral tolerance
therapy can effectively prevent, and in some cases decrease,
exacerbations of disease.

In one particularly interesting study, investigators found that
they could prevent the onset of a multiple sclerosis-like
illness in mice by feeding them an antigen that is not involved
in the disease process. Apparently, this antigen stimulated the
production of "suppressor" T cells. The suppressor cells then
migrated to the diseased tissues, where they decreased the
activity of the T cells that were involved in the illness.
Since it does not appear that scientists must first identify
the specific autoantigens involved in a particular autoimmune
disease--something that is rarely known --- the likelihood of
the success of oral tolerance therapy in humans is encouraging.

Preliminary studies in humans also have had promising results.
In one trial, eight men with multiple sclerosis received daily
doses of the protein myelin. Over the course of a year, none of
them had a relapse, while two of the three men who received a
placebo suffered frequent relapses. (The treatment did not,
however, demonstrate favorable effects in women.) In a trial
involving 60 patients with rheumatoid arthritis, disease
severity diminished in patients who received oral tolerance
therapy; four attained total clinical remission. The
investigators reported that patients tended to relapse when
they were taken off the feeding regimen, results that are borne
out by the multiple sclerosis trial and an ongoing study on
uveitis. But, since patients do not appear to suffer allergic
reactions, this therapy seems to be safe for trials of
long-term treatment.

Future Directions

The exciting implications of animal and human studies is that
oral feeding of proteins may be a safe and effective treatment
for several forms of autoimmune disease. Ultimately, it may be
possible that people with Crohn's disease or ulcerative colitis
may be fed a combination of proteins from the small or large
intestine, respectively.

As with all new approaches, scientists will need to exercise
some caution as they initiate these trials, to avoid unexpected
side effects. Among the key questions they must answer is
whether this therapy must be continued indefinitely in order to
avoid relapses of disease.

Copyright © 1996 by Crohn's & Colitis Foundation of America, Inc.

TO British Columbia IBS folks: New Drug
Mon, 3 Mar 1997 4:16:22 GMT

Jim Prousalis recently sent out a message on a new drug called ISIS 2302. The preliminary results seem very impressive. I live in the Seattle area. If the drug has success, I can expect the US FDA to
release it some time in the next decade or so. Jim has stated that the drug may be available by the end of 1997.

I know that is quite a while off, but, when it becomes available, if any of you in BC have your doctor prescribe the drug or know of a doctor which is prescribing the drug as it comes out, would you please try to remember this E-mail and drop me a line. It is a day trip for me to Canada and, if the trials following this are as promising, I want very much to give this a try.

I have put a note in my schedule to re-send an inquiry in early January.

Thanks... Kim.

Info On ISIS That May be of Interest from the IBD Diigest
From: Harry Hollenberg,
Subject: ISIS 2302
Date: Fri, 14 Mar 1997 15:31:00 -0500

I hope this isn't too long for the list, but I saw some questions about it, so I thought the group would be interested.

- Harry Hollenberg

300 Patient, Pivotal-Quality Study to Begin in Early Second Quarter 1997

CARLSBAD, Calif., and INGELHEIM, Germany, Feb. 27, 1997 / PRNewswire / -- Isis
Pharmaceuticals (Nasdaq: ISIP) and Boehringer Ingelheim will present
data tomorrow showing that ISIS 2302, an antisense anti-inflammatory
drug, demonstrated safety and efficacy in a Phase II study of patients
with Crohn's disease, a form of inflammatory bowel disease. The positive
results of this study are the first evidence of therapeutic benefit with
a systemically administered antisense drug and form the basis for the
decision by Isis and its partner, Boehringer Ingelheim, to proceed with
full-scale development of ISIS 2302 in Crohn's disease.

In this randomized, double-blinded, placebo-controlled study, 47% of
patients treated with ISIS 2302 were in disease remission versus 0% in
the placebo group at the end of the one-month treatment phase. The mean
duration of remission in the responding patients was prolonged, lasting
almost five months following a single course of treatment. In addition,
a statistically significant lowering of corticosteroid requirements was
achieved in the ISIS 2302 treated group from Month 1 through the end of
the study at six months (p=0.0001).

Study Design
Speaking at the Canadian Digestive Diseases Week conference in Quebec
City, Quebec, Canada, the clinical investigator on the ISIS 2302 Crohn's
disease study, Bruce R. Yacyshyn, M.D., of the Division of
Gastroenterology, Department of Medicine of the University of Alberta,
will present data from a placebo-controlled study of 20 patients with
steroid dependent Crohn's disease. The patients were randomized in a
three-to-one (3:1) ratio of drug to placebo. Efficacy was assessed by
change from baseline in three indices: the Crohn's Disease Activity
Index (CDAI), a clinical scoring scale; the Endoscopic Index of Severity
(EIS), based on colonoscopic examination; and the Inflammatory Bowel
Disease Questionnaire (IBDQ), a quality of life scale. Changes in
corticosteroid requirements were also recorded and analyzed.

Patients were evaluated at intervals during the four-week treatment
phase and then for six months, or until disease progression was
documented, to determine the kinetics and duration of response. During
the treatment phase, patients were intravenously administered ISIS 2302
or saline placebo every other day for two weeks and then three times per
week for an additional two weeks, for a total of 13 infusions over a
26-day period. The doses ranged from 0.5 mg/kg to 2 mg/kg, with the
first four patients assigned to the 0.5 mg/kg group, the second four
patients assigned to the 1 mg/kg group and the remaining 12 patients to
the 2 mg/kg group.

Study Results
Study results showed that the clinical scoring (CDAI) trends clearly
favored ISIS 2302 over placebo in both magnitude and duration of
response. These trends were supported by similar trends in EIS and IBDQ
assessments, and, most importantly, by significantly lower (p=0.0001)
steroid requirements in the ISIS 2302 group than in the placebo group
from the first through the sixth month of the study. There was no
evidence of a dose response for any of the measurement indices, most
likely due to the relatively narrow range of doses and the small number
of patients within each dosage group. The study also showed that ISIS
2302 was safe and well-tolerated.

CDAI scores can range from approximately 0-600. A score of <150 is
considered a remission. In this study, at the end of one month of
therapy, 47% of the ISIS 2302 treated patients were in remission
(CDAI<150) versus none of the placebo group. Although improvements in
CDAI were seen at the end of the first week of treatment, in the
remitting patients the mean time to remission was 24.9 days. The mean
duration of remission for ISIS 2302 responding patients was 147.6 days.

Most remarkable for a small trial, strongly statistically lower steroid
requirements for the ISIS 2302 group than for the placebo group were
observed. At the end of the trial, five of 15 patients (33%) were
completely weaned from corticosteroids compared to zero placebo

Significance of the Results
"The safety and efficacy results from this Phase II study in Crohn's
disease are extremely encouraging for patients with Crohn's disease and
for their physicians," said Daniel Kisner, M.D., President and Chief
Operating Officer. "Crohn's disease is a serious, debilitating, chronic
disease that affects hundreds of thousands of people all over the world
in the prime of their lives and for which current treatments such as
steroids and immunosuppressive agents are often ineffective and highly
toxic. The data show that ISIS 2302 can induce high levels of response
and disease remission, and, even more remarkable, that patients can be
weaned from dependency on steroids. We are eager to initiate a pivotal
quality study of ISIS 2302 in Crohn's disease within the next one to two

"Isis and Boehringer Ingelheim are very excited by the safety and
efficacy results of this Phase II study of our first systemically
administered antisense drug as they confirm the specificity and
selectivity of antisense drugs and the importance of ICAM-1 as a target
in inflammatory diseases," said Stanley Crooke, M.D., Ph.D., Chairman
and Chief Executive Officer. "Combined with the safety and efficacy
profile of ISIS 2922, a locally administered drug for CMV retinitis in
AIDS patients, the ISIS 2302 data show that antisense drugs can achieve
significant therapeutic benefit with an attractive safety profile, and
that antisense technology is succeeding as an effective and productive
drug discovery platform."

ISIS 2302 is an antisense inhibitor of ICAM-1, a cell adhesion molecule
implicated in a wide range of inflammatory diseases and conditions. Isis
plans to initiate a multi-center, 300-patient, pivotal quality study of
ISIS 2302 in Crohn's disease in the second quarter of this year. ISIS
2302 is in Phase II trials in four indications in addition to Crohn's
disease: rheumatoid arthritis, psoriasis, ulcerative colitis and
prevention of kidney transplant rejection. Results from these four
trials are anticipated throughout 1997. ISIS 2302 is a key asset in the
cell adhesion drug discovery and development collaboration established
in 1995 between Isis and Boehringer Ingelheim. Isis and Boehringer
Ingelheim will make a determination concerning further development of
ISIS 2302 based on the drug's performance in these studies.

Patients and physicians who are interested in obtaining additional
information about the Phase II clinical trials of ISIS 2302 in Crohn's
disease that will begin in the second quarter of 1997 should contact

Fri, 11 Apr 1997 21:02:53 GMT

I don't know if you are up on this treatment of Centocor's, but this came out yesterday-

CentoCor's CA2 -2:Confirms Effectiveness In Closing Fistulae

MALVERN, Pa. (Dow Jones) - - Centocor Inc. (CNTO) said data from a trial in patients with Crohn's disease showed treatment with its CA2 monoclonal antibody, or CenTNF, produced a ''statistically significant positive result.''

In a press release Friday, Centocor said the trial's primary goal was closure of at least 50% of open fistulae.

The company said the data demonstrated that CA2 is useful in treating a severe complication in Crohn's disease patients, and it will work to bring the product to market as quickly as possible.

The trial studied the clinical benefit of CA2 among 94 patients suffering from Crohn's disease who had enterocutaneous fistulae, a complication of the disease in which extensions occur between the bowel and the skin, allowing drainage of mucous and fecal material.

The company said the results confirm findings from earlier studies which show that Crohn's disease can be brought under control and, in some cases, into remission with the use of the drug.

Full results of this study will be released later in the year.

The drug will add an inflammatory disease product to CentoCor's pipeline of therapeutic products, which includes cardiovascular diseases and cancer products.

Centocor develops and commercializes therapeutic and diagnostic products and services.

11:34 040497

Good Luck


The Paleodiet List-server group has a continual discussion about the absence of grains in the early Man's diet.
A letter from the discussion is placed here.

Intestinal Dysbiosis and the Causes of Disease

by Leo Galland, MD, and Stephen Barrie, ND.

(Note: For use by & dissemination to members of the "Specific Carbohydrate Diet" list-server only, by permission of Dr. Stephen Barrie, as of November 1997. Placed on this web site on Saturday, 3 January 1998)

Leo Galland is Senior Research Consultant and Stephen Barrie, President, at Great Smokies Diagnostic Laboratory, 18A Regent Park Boulevard, Asheville, North Carolina 28806.


With the advent of biochemical and microbial stool analysis panels, an increasing number of physicians are seeking a clearer understanding of the relationship between the ecology of the digestive tract and local and systemic factors affecting health and disease. It can be described as being due to either putrefaction, fermentation, deficiency, or sensitization. A number of inflammatory diseases within the bowel or involving skin and connective tissue have been reported in association with dysbiosis. This article details the relationships, causes, and treatment options for dysbiotic-related conditions.



Recognition that intestinal flora have a major impact on human health first developed with the birth of microbiology in the late nineteenth century. It is generally accepted that our relationship with indigenous gut flora is eu-symbiotic, meaning a state of living together that is beneficial. Metchnikoff popularized the idea of "Dys-symbiosis, or Dysbiosis", a state of living with intestinal flora that has harmful effects. He postulated that toxic amines produced by bacterial putrefaction of food were the cause of degenerative diseases, and that ingestion of fermented foods containing Lactobacilli could prolong life by decreasing gut putrefaction (1). Although Metchnikoff's ideas have been largely ignored in the United States, they have influenced four generations of European physicians. The notion that dysbiotic relationships with gut microflora may influence the development of inflammatory diseases and cancer has received considerable experimental support over the past two decades, but the mechanisms involved are far more diverse than Metchnikoff imagined.

The stool of healthy human beings consuming a Western diet contains 2.4 x 1050 bacteria per gram. Twenty species comprise 75% of the total number of colonies; non-spore forming anaerobes predominate over aerobes by a ratio of 5,000:1 (2). Organisms cultured from mucosal surfaces are significantly different from those found in stool and vary among different parts of the gastrointestinal tract. The bacterial concentration in the stomach and small intestine is several orders of magnitude less than in the colon. The major mucosal organisms there are coccobacilli (1) and streptococci (3). The predominant organisms cultured from the gastric and duodenal aspirates are yeasts and Lactobacilli (2), living in the lumen. In the colon, the presence of these organisms is overshadowed by spirochetes and fusiform bacteria on the mucosal surface, and anaerobic rods like Eubacterium, Bacteroides, and Bifidobacterium in the lumen. Benefits and adverse effects of the normal gut microflora are listed in Tables 1 and 2 and have been described elsewhere (4).

Materials and Methods

Clinical Assessment

Intestinal dysbiosis should be considered as a mechanism promoting disease in all patients with chronic gastrointestinal, inflammatory, or autoimmune disorders, food allergy, and intolerance, breast and colon cancer, and unexplained fatigue, malnutrition or neuro-psychiatric symptoms.

Table 1: Benefits of Normal Gut Flora

Synthesize vitamins - biotin, cobalamin, pantothenic acid, pyridoxine, riboflavin, vitamin K.

Synthesize short chain fatty acids (SCFA) - butyrate, propionate, and acetate.

Degrade toxins and xenobiotics.

Prevent colonization by pathogens.

Stimulate maturation of normal immune responses.

Table 2: Adverse Effects of Normal Gut FloraDeactivate trypsin and chymotrypsin.

Consume vitamin B12.

Produce ammonia.

Inactivate brush border enzymes.

Desaturate bile steroids.

Deconjugate bile acids and estrogens.

Activate pro-carcinogens.

Degrade dietary flavonoids.

Create secondary bile acids.

Activate proto-carcinogens.

Stimulate dysfunctional immune responses.

Hydrogenate dietary PUFAs (poly-unsaturated fatty acids).

Convert amino acids to amines and phenols.


The most useful test for this condition is a Comprehensive Digestive Stool Analysis (CDSA), which includes:

a) biochemical measurements of digestion / mal-digestion (fecal chymotrypsin, fecal triglycerides, meat and vegetable fibers, pH), intestinal absorption / malabsorption (long chain fatty acids, fecal cholesterol, and total short chain fatty acids)

b) metabolic markers of intestinal metabolism

c) identification of the bacterial microflora, including friendly, pathogenic and imbalanced flora

d) detection of abnormal gut mycology

[.... Interpretation of Gut Dysbiosis Score & Table 3]


Based on available research and clinical data, we now believe that there are four patterns of intestinal dysbiosis: putrefaction, fermentation, deficiency, and sensitization.


This is the classic Western degenerative disease pattern advanced by Metchnikoff. Putrefaction dysbiosis results from diets high in fat and animal flesh and low in insoluble fiber. This type of diet produces an increased concentration of Bacteroides sp. and a decreased concentration of Bifidobacteria sp. in stool. It increases bile flow and induces bacterial urease activity 1. The alterations in bacterial population dynamics which result from this diet are not measured directly by the [Comprehensive Digestive Stool Analysis (CDSA)]. The changes occur primarily among anaerobes, but the effects are measured in an increase in stool pH (partly caused by elevated ammonia production) and in bile or urobilinogen and possibly by a decrease in short chain fatty acids, especially in butyrate. Epidemiologic and experimental data implicate this type of dysbiosis in the pathogenesis of colon cancer and breast cancer (5).

A putrefaction dysbiosis is accompanied by an increase in fecal concentrations of various bacterial enzymes which metabolize bile acids to tumor promoters and deconjugate excreted estrogens, raising the plasma estrogen level (6).

Putrefaction dysbiosis is corrected by decreasing dietary fat and flesh, increasing fiber consumption and feeding Bifidobacteria and Lactobacillus preparations. Most adverse effects of the indigenous gut flora are caused by intense metabolic activity of luminal organisms.

The following are associated with Putrefaction dysbiosis.

1. The enzyme urease, found in Bacteroides, Proteus, and Klebsiella species, and induced in those organisms by a diet high in meat, hydrolyzes urea to ammonia, raising stool pH. A relatively high stool pH is associated with a higher prevalence of colon cancer (7).

2. Bacterial decarboxylation of amino acids yields vasoactive and neurotoxic amines, including histamine, octopamine, tyramine, and tryptamine; these are absorbed through the portal circulation and deaminated in the liver. In severe cirrhosis they reach the systemic circulation and contribute to the encephalopathy and hypotension or hepatic failure (1).

3. Bacterial tryptophanase degrades tryptophan to carcinogenic phenols, and, like urease, is induced by a high meat diet (8).

4. Bacterial enzymes like beta-glucuronidase hydrolyze conjugated estrogens and bile acids. Hepatic conjugation and biliary excretion is an important mechanism for regulating estrogen levels in the body. Bacterial deconjugation increases the enterohepatic recirculation of estrogen. A Western diet increases the level of deconjugating enzymes in stool, lowers estrogen levels in stool and raises estrogen levels in blood and urine, possibly contributing to the development of breast cancer (6).

5. Beta-glucuronidase and other hydrolytic bacterial enzymes also deconjugate bile acids.

Deconjugated bile acids are toxic to the colonic epithelium and cause diarrhea. They or their metabolites appear to be carcinogenic and are thought to contribute to the development of colon cancer (6, 9) and to ulcerative colitis (10). Gut bacteria also reduce primary bile acids like cholate and chenodeoxycholate to secondary bile acids like deoxycholate (DCA) and lithocholate. The secondary bile acids are absorbed less efficiently than primary bile acids and are more likely to contribute to colon carcinogenesis. The prevalence of colon cancer is proportional to stool concentration of DCA. Not all bacterial enzyme activity is harmful to the host. Fermentation of soluble fiber by Bifidobacteria sp. yields SCFA (short chain fatty acids). Recent interest has focused on the beneficial role of short-chain fatty acids like butyrate in nourishing healthy colonic mucosal cells. Butyrate has been shown to induce differentiation of neoplastic cells (11), decrease absorption of ammonia from the intestine (1), decrease inflammation in ulcerative colitis (12) and, following absorption, decrease cholesterol synthesis in the liver (7). Butyrate lowers the stool pH. A relatively low stool pH is associated with protection against colon cancer (5). The principal source of colonic butyrate is fermentation of soluble fiber by colonic anaerobes. Thus, putrefaction dysbiosis results from the interplay of bacteria and diet in their effects on health and disease.


This is a condition of carbohydrate intolerance induced by overgrowth of endogenous bacteria in the stomach, small intestine, and cecum. The causes and effects of small bowel bacterial overgrowth have been well characterized. Bacterial overgrowth is promoted by gastric hypochlorhydria, by stasis due to abnormal motility, strictures, fistulae, and surgical blind loops, by immune deficiency or by malnutrition (13).

Small bowel parasitosis may also predispose to bacterial overgrowth (4). Some of the damage resulting from small bowel bacterial overgrowth is produced by the action of bacterial proteases which degrade pancreatic and intestinal brush border enzymes causing pancreatic insufficiency, mucosal damage and malabsorption. In more severe cases the intestinal villi are blunted and broadened and mononuclear cells infiltrate the lamina propria. Increased fecal nitrogen leads to hypoalbuminemia. Bacterial consumption of cobalamin lowers blood levels of vitamin B12. Bile salt dehydroxylation impairs micelle formation (10). Endotoxemia resulting from bacterial overgrowth contributes to hepatic damage in experimental animals (4). Gastric bacterial overgrowth increases the risk of systemic infection. Gastric bacteria convert dietary nitrates to nitrogen and nitrosamines; hence, the increased risk of gastric cancer in individuals with hypochlorhydria (15).

Some bacterial infections of the small bowel increase passive intestinal permeability (16). Carbohydrate intolerance may be the only symptom of bacterial overgrowth making it indistinguishable from intestinal candidosis; in either case, dietary sugars can be fermented to produce endogenous ethanol (17, 18). Chronic exposure of the small bowel to ethanol may itself impair intestinal permeability (19). Another product of bacterial fermentation of sugar is D-lactic acid. Although D-lactic acidosis is usually a complication of short-bowel syndrome or of jejuno-ileal by-pass surgery (colonic bacteria being the source of acidosis), elevated levels of D-lactate were found in blood samples of 1.12% of randomly selected hospitalized patients with no history of gastro-intestinal surgery or disease (20).

Small bowel fermentation is a likely cause of D-lactic acidosis in these patients. British physicians working with the gut-fermentation syndrome as described by Hunisett et al (18) tentatively concluded, based on treatment results, that the majority of cases are due to yeast overgrowth and about 20% are bacterial in origin. The symptoms include abdominal distention, carbohydrate intolerance, fatigue, and impaired cognitive function.


Exposure to antibiotics or a diet depleted of soluble fiber may create an absolute deficiency of normal fecal flora, including Bifidobacteria, Lactobacillus, and E. Coli. Direct evidence of this condition is seen on stool culture when concentration of Lactobacillus or E. Coli are reduced. Low fecal short chain fatty acids provide presumptive evidence. This condition has been described in patients with irritable bowel syndrome and food intolerance [...]. Deficiency and putrefaction dysbiosis are complementary conditions which often occur together and have the same treatment.


Aggravation of abnormal immune responses to components of the normal indigenous intestinal microflora may contribute to the pathogenesis of inflammatory bowel disease, spondyloarthropathies, other connective tissue disease and skin disorders like psoriasis or acne. The responsible bacterial components include endotoxins, which can activate the alternative complement pathway, and antigens, some of which may cross-react with mammalian antigens. Treatment studies in ankylosing spondylitis and inflammatory bowel disease suggest that sensitization may complement fermentation excess and that similar treatments may benefit both conditions. Clinical research has implicated bacterial dysbiosis in a number of diseases of inflammation within the bowel or involving skin or connective tissue. [...]

Atopic Eczema

Ionescu and his colleagues have studied fecal and duodenal flora in patients with atopic eczema and found evidence of small bowel dysbiosis and subtle malabsorption phenomena in the majority (21, 22). Treatment with antibiotics or with a natural antibiotic derived from grapefruit seeds, produced major improvement in the gastro-intestinal symptoms of eczema patients and moderate improvement in severity of eczema (23). One advantage in the use of grapefruit seed extract over conventional antibiotics lies in its anti-fungal activity. This agent adds a second therapeutic dimension and eliminates the possibility of secondary candidosis. The minimum effective dose of grapefruit seed extract for bacterial dysbiosis is 600mg a day.

Irritable Bowel Syndrome

Hunter and his colleagues have studied patients with the irritable bowel syndrome in whom diarrhea, cramps, and specific food intolerances are major symptoms (24). They have found abnormal fecal flora to be a consistent finding, with a decrease in the ratio of anaerobes to aerobes, apparently due to a deficiency of anaerobic flora (25, 26). Previous exposure to antibiotics, metronidazole in particular, was associated with the development of this disorder (27).

Inflammatory Bowel Disease

Two decades ago, exaggerated immunologic responses to components of the normal fecal flora were proposed as possible mechanisms in the etiology of inflammatory bowel disease (28). Little progress has been made in confirming or disproving this theory, although bacterial overgrowth of the jejunum has been found in 30% of patients hospitalized for Crohn's disease, in which it contributes to diarrhea and malabsorption (29).

The demonstration of increased intestinal permeability in patients with active Crohn's disease and in healthy first- degree relatives suggests the existence of a pre-existing abnormality that allows an exaggerated immune response to normal gut contents to occur (30). It is interesting to note that elemental diets can induce remission in Crohn's disease as effectively as prednisone. The chief bacteriologic effect of elemental diets is to lower the concentration of Lactobacilli in stool drastically without altering the levels of other bacteria (31). It is well-known that many patients with Crohn's disease can be brought into remission with metronidazole, tetracycline, and other antibiotics. In ulcerative colitis, colonic damage from toxic metabolites of bile acids has been suggested (9). Alpha-tocopherylquinone, a vitamin E derivative that antagonizes vitamin K-dependent bacterial enzymes, reversed ulcerative colitis dramatically in one subject (32).

Drawing on much broader experience with inflammatory bowel disease, Gottschall has proposed that gut dysbiosis plays the major etiologic role, with small and large bowel fermentation being a key component. She has used a "specific carbohydrate diet" restricted in disaccharide sugars and devoid of cereal grains to alter gut flora (33). Some will undoubtedly argue that Gottschall's success is due to food allergen elimination, but the time course of patients' responses is more consistent with the author's contention that a gradual alteration of gut flora content is the mechanism.

McCann has pioneered a dramatic, experimental treatment for inflammatory bowel disease which has induced a rapid remission in 16 out of 20 patients with ulcerative colitis. A two-day course of multiple broad-spectrum antibiotics to decontaminate the gut is followed by administration of defined strains of Escherichia coli and Lactobacillus acidophillus to produce a reflorastation of the colon (24).

Arthritis and Ankylosing SpondylitisImmunologic responses to gut flora have been advanced by several authors as important factors in the pathogenesis of inflammatory joint diseases. It is well known that reactive arthritis can be activated by intestinal infections with Yersinia, Salmonella, and other enterobacteria (35). In some cases bacterial antigens have been found in synovial cells (36, 37) and may enter the circulation because of the increased intestinal permeability associated with the intestinal infection (15). Increased intestinal permeability and immune responses to bacterial debris may cause other types of inflammatory joint disease as well, but there is little evidence of the frequency with which this occurs (38, 39, 40). Several groups have proposed a specific mechanism by which Klebsiella pneumoniae may provoke ankylosing spondylitis (41, 42, 43).

HLA-B27 is expressed on the lymphocytes of synovial cells on 97% of patients with ankylosing spondylitis. This antigen cross-reacts with antigens found on Klebsiella pneumoniae and possibly other enterobacteria. Patients with ankylosing spondylitis have higher levels of anti-Klebsiella IgA in plasma than do controls. Patients who are HLA-B27 positive but who do not have ankylosing spondylitis, do not have Klebsiella in their stools or Klebsiella antibodies in their plasma.

Molecular mimicry appears to be the mechanism by which intestinal enterobacteria cause ankylosing spondylitis in genetically susceptible individuals. Ebringer has successfully treated ankylosing spondylitis with a low starch diet similar to Gottschall's regimen for bowel disease. This diet lowers the concentration of Klebsiella in stool and decreases the titre of anti-Klebsiella IgA. He has also proposed that rheumatoid arthritis, which it associated with HLA-DR4, involves a similar molecular mimicry between HLA-DR4 and Proteus mirabilis, as cross-reactive Proteus antibodies are higher in patients with rheumatoid arthritis than in controls.

Abnormal immune responses to components of the normal gut flora represents a form of dysbiosis which suggests a novel treatment for inflammatory diseases.

Treatment Approaches

Diet - Putrefaction dysbiosis is usually managed with a diet high in both soluble and insoluble fiber and low in saturated fat and animal protein. Dairy products have a variable effect; fermented dairy foods like fresh home-made or "live bacteria" yogurt are occasionally helpful. These dietary changes work to lower the concentration of Bacteroides and increase concentrations of lactic acid-producing bacteria (Bifidobacteria, Lactobacillus, and lactic acid streptococci) in the colon (44, 45). Supplementing the diet with defined sources of fiber can have variable effects on colonic dysbiosis. Insoluble fiber decreases bacterial concentration and microbial enzyme activity (46, 47). Soluble fiber, on the other hand, tends to elevate bacterial concentration and enzyme activity at the same time that it raises the levels of beneficial short chain fatty acids. This disparity may explain the superior effect of insoluble fiber in the prevention of colon cancer (48, 49, 50, 51). Fructose-containing oligosaccharides, found in vegetables like onion and asparagus, have been developed as a food supplement for raising stool levels of Bifodobacteria and lower stool pH (52).

In fermentation dysbiosis, by contrast, starch and soluble fiber may exacerbate the abnormal gut ecology (3, 33). When the upper small bowel is involved, simple sugars are also contra-indicated. A diet free of cereal grains and added sugar is generally the most helpful. Fruit, fat, and starchy vegetables are tolerated to a variable degree in different cases. Oligosaccharides found in some vegetables, carrots in particular, inhibit the binding of enterobacteria to the intestinal mucosa. Carrot juice and concentrated carrot oligosaccharides have been used in Europe for bacterial diarrhea for almost a century (53).

Biotherapies - Administration of bacterial indigenous to the healthy human colon can reverse relapsing Clostridium difficile infection (54). Lactobaccillus administration has long been used in an attempt to improve gut microbial ecology. Regular ingestion of acidophilus milk lowers stool concentration of urease-positive organisms and of bacterial enzymes which may contribute to carcinogenesis (55). Fermented dairy products and lyophilized Lactobacillus preparations have been shown to be useful in treating and preventing salmonellosis, shigellosis, antibiotic-induced diarrhea, and in inhibiting tumor growth (56). Problems with Lactobacilli include the failure of organisms to adhere to the intestinal mucosa or to survive damage from gastric acid and bile. The acidophilus sweepstakes has led to the search for newer and better strains for medical uses (57, 58). Bifidobacteria are the predominant lactic acid bacteria of the colon with a concentration that is 1000 times greater than Lactobacilli. Administration of Bifidobacterium brevum to humans and to non-human animals reduces fecal concentrations of Clostridia and Enterobacter species, ammonia, and toxigenic bacterial enzymes including beta-glucuronidase and tryptophanase; urinary indican is also lowered (59). Administration of defined strains of E. Coli and Enterococcus for the purpose of altering gut flora has been popular in Europe, but documentation of the health effects is scanty.

Bacillus laterosporus, a novel organism classified as non-pathogenic to humans (60), produces unique metabolites with antibiotic, anti-tumor, and immune-modulating activity (61, 62, 63). This organism has been available as a food supplement in the Untied States for about 5 years. We have found it to be an effective adjunctive treatment for control of symptoms associated with small bowel dysbiosis in a number of patients.

Of equal interest, and more thoroughly researched, a yeast, Saccharomyces boulardii, has been used in Europe for control of non-specific diarrhea for several decades. Originally isolated from Indo-Chinese leechee nuts, S. boulardii is grown and packaged as a medication in France, where it is popularly called "Yeast Against Yeast". Controlled studies have demonstrated its effectiveness in preventing antibiotic-associated diarrhea and Clostridium difficile colitis (64, 65). S. boulardii has also been shown to stimulate production of secretory IgA in rats (65). Immune-enhancing therapy of this type may be contra-indicated in patients suffering from reactive arthritis and other diseases in which an exaggerated intestinal immune response is found.


Antibiotic drugs may either cause or help control dysbiosis, depending upon the drug and the nature of the disorder. Where contamination of the small bowel by anaerobes is the problem, metronidazole or tetracyclines may be beneficial. When enterobacterial overgrowth predominates, ciprofloxacin is usually the drug of choice because it tends to spare anaerobes. Herbal antibiotics may be preferred because of their greater margin of safety and the need for prolonged antimicrobial therapy in bacterial overgrowth syndromes. Citrus seed extract may be a desirable first line of treatment because of its broad spectrum of antibacterial, anti-fungal, and anti-protozoan effects (23). The usual dose required is 600 to 1600 mg per day. Animal studies have shown no toxicity except for intestinal irritation producing diarrhea at very high doses. The mechanism of action is not known; there is no evidence of systemic absorption.

Bayberry leaf, containing the alkaloid berberine, appears to be cidal for enterobacteria, yeasts, and amoebae. The control of dysbiotic symptoms usually requires several grams a day.

Artemesia annua has primarily been used for treatment of protozoan infection (67). The most active ingredient, artemisinin, is a potent pro-oxidant whose activity is enhanced by polyunsaturated fats like cod liver oil and antagonized by vitamin E (68). Artemisinin is used intravenously in Southeast Asia for the treatment of cerebral malaria; it has no known deleterious side-effects except for induction of abortion when used in high doses in pregnant animals.

The herbal pharmacopoeia lists many substances with natural antibiotic activity, and the potential for herbal treatment of gut dysbiosis is virtually unlimited. A tannin-rich mixture of herbal concentrates including extracts of gentiana, sanguinaria, and hydrastis has been marketed under various names. In-vitro studies at Great Smokies Diagnostic Laboratory have found this mixture to exert more potent activity against enterobacteriaceae and Staphylococcus than any of the common antibiotic drugs tested; its major side-effect is nausea produced by the high tannin content.

Summary and Conclusions

Altered microbial ecology in the gut may produce disease and dysfunction because of the intense metabolic activity and antigenicity of the bacteria flora. Bacterial enzymes can degrade pancreatic enzymes, damage the intestinal brush border, deconjugate and reduce bile acids, and alter the intestinal milieu in numerous ways, some of which can be easily measured in a properly-collected sample of stool. Bacterial antigens may elicit dysfunctional immune responses which contribute to autoimmune diseases of the bowel and of connective tissue. Effective treatment of dysbiosis with diet, antimicrobial substances, and biotherapies must distinguish among patterns of dysbiosis. The failure of common approaches utilizing fiber and Lactobacilli is a strong indication of small bowel bacterial overgrowth, a challenging disorder which demands a radically different approach.

*** Bibliography (68 references, approx. 2 pages) available on request from members of the list-server.

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Irritable Bowel Not To Be Dismissed

Friday December 5 5:10 PM EST

NEW YORK (Reuters) -- A report in this week's issue of The Lancet is
urging doctors to take patients diagnosed with
irritable bowel syndrome (IBS) more seriously.

Although no solid medical explanation currently exists for the bouts
of abdominal cramps, constipation, and diarrhea usually associated
with the problem, patients should not be dismissed by their
physicians as hypochondriacs with no serious medical problems.

"IBS is a chronic relapsing condition, and some suggest it occurs
in most adults at some point in their lives," write Drs. Paul Maxwell
and M.A. Mendell, and Mr. D. Kumar, the authors from St. George's
Hospital Medical School in London, and Mayday University Hospital in
Surrey, U.K. They also point out that the problem is the cause of
20% to 50% of referrals to gastroenterology clinics.

The authors note a long-standing belief among doctors that patients
with IBS are hypochondriac, hysterical, or depressed. "Many physicians
today hold these beliefs so strongly that they almost disregard the
gastrointestinal complaints of their IBS patients," they state.

Such beliefs have sparked numerous studies at an attempt to link IBS
with the psychological make-up of patients,
but "results, however, are conflicting."

Some patients who "are fixed in their belief that they have cancer,"
may not improve until their fears have been set aside by further tests,
including exams of the bowel (barium enema and colonoscopy).

"Drug treatment should be directed toward the most troublesome symptoms,"
the authors state. Dietary recommendations to relieve constipation
(increase fiber intake), diarrhea (reduce dietary fat), and abdominal
cramps (reduce tea and coffee) may be effective.

"Some patients can gain substantial benefit from alternative therapies,
such as behavioral therapy or biofeedback, stress management,
and hypnosis," they add.

"There is no easy treatment for IBS, and no cure. The diagnosis marks
the beginning of a long physician-patient relationship, which is as
vital as any medication," the report says.

SOURCE: The Lancet (1997;350:1691-1695)

Date: Sat, 10 Jan 98 16:16:23 CST
From: (Ted Kyle)

very interesting, and it's "from" the CDC web site, look here also if you have any of the various forms of arthritis. i think elains diet or the Lutz diet could work simply by avoiding carbohydrate rich meals (which will blunt your immune system for about 2 hours) we strengthen our immune system and thus fight off the bacteria, this could also explain the 2-4 month flare that accompanies the diet, your immune system is stronger so the inflammation gets worse, until you get over the hump with the infection. Lutz noted this type response in his book and sometimes used gold to depress the immune system somewhat until things got better.


Inflammatory Bowel Disease

Inflammatory bowel disease is the collective term for Crohn disease and ulcerative colitis. While both infections are chronic inflammatory diseases with histologic infiltrates of macrophages and lymphocytes and a prolonged clinical course, the primary clinical and pathologic effects are gastrointestinal. The infections can be difficult to differentiate because the symptoms are often similar (15). The acute clinical characteristics are diarrhea, abdominal pain, fever, and weight loss; and the acute pathologic features include a constant flux of neutrophils into inflamed mucosa, eventually penetrating the epithelium into the intestinal lumen. The chronic spontaneously relapsing disorder exhibits many of the symptoms of the acute state; however, this phase has an average symptom duration of 3.2 years before correct diagnosis. Abdominal abscesses are a common and dangerous complication of Crohn disease, while in ulcerative colitis, abdominal perforations may lead to peritonitis. Crohn disease involves the ileum or colon (anaerobes are important), while ulcerative colitis appears restricted to the colon (aerobes are important). Nationality and familial associations suggest a genetic predisposition for the disease (4,15).

Although the cause of inflammatory bowel disease and the mechanism(s) for spontaneous exacerbations and remissions are unknown, much research has focused on transmissible agents, including foodborne pathogens. An association between bacterial L-forms and inflammatory bowel disease has been sporadically reported, with isolation of Pseudomonas, Mycobacterium, Enterococcus fecalis, and E. coli from affected tissue but not from appropriate controls. There is considerable debate as to whether L-forms are pathogenic in humans or persist in affected tissue.

Mycobacterium paratuberculosis, the causative agent of Johne disease in ruminants, may be associated with Crohn disease through the production of L-forms of the bacterium. Subclinically infected cows shed M. paratuberculosis, and the organism has been identified in pasteurized milk by polymerase chain reaction specific for the M. paratuberculosis insertion sequence IS900. The pathogen model suggests that a susceptible human neonate first contracts the organism after ingesting commercial dairy products. This invokes an antigen-poor (lacking a cell wall) L-form that grows slowly and persists in the lamina propria, stimulating a chronic low-grade inflammation. The immune response increases in severity over years without bacterial replication, ultimately producing the pathologic features of Crohn disease (15,16). Another model proposes an autoimmune phenomenon mediated by alterations in inflammatory cytokine profiles, possibly as a result of infection (4).

Recent immunocytochemical techniques demonstrated antigens to Listeria monocytogenes, E. coli, and Streptococcus spp. in Crohn disease tissues. Macrophages and giant cells immunolabelled for antigen specific to these organisms were found beneath ulcers, around abscesses, along fissures, within the lamina propria, in granulomas, and in germinal centers of mesenteric lymph nodes (17).

I recently accidently came across a guy, a Phd, who works at the London School of Hygiene and Tropical Medicine who sent me an abstract on new research linking Blastocystis and IBD from 'Medline'. I think it's fairly recent. The research was conducted in Pakistan and London. Thought some of you may have been diagnosed with this particular parasite so here goes:

Significantly increased IgG2 subclass antibody levels to Blastocystis hominis in patients with irritable bowel syndrome.

Am J Trop Med Hyg 1997 Mar;56(3):301-306

By Hussain R, Jaferi W, Zuberi S, Baqai R, Abrar N, Ahmed A, Zaman V

Blastocystis hominis is a common intestinal parasite of humans in the tropics whose pathogenic role is in dispute. Its presence has been reported in a variety of intestinal disorders resembling irritable bowel syndrome (IBS) such as diarrhea, anorexia, and flatulence. We have therefore investigated a possible link between IBS and blastocystosis by determining IgG antibody levels to B. hominis in patients with IBS. Levels of IgG antibodies were significantly elevated in patients with IBS compared with asymptomatic controls (P < 0.0001, by Student's t-test) in both B. hominis stool culture-positive and stool culture-negative IBS patients. When IgG antibodies were divided into their respective subclasses, only IgG2 levels were significantly increased in IBS patients compared with asymptomatic controls, indicating that the predominant response in these patients may be directed to carbohydrate antigens. The diagnostic usefulness of this test in IBS patients remains to be established because these data are only suggestive of a possible link between B. hominis and IBS. However, we hope that this antibody test will help in elucidating the controversy that surrounds the role of B. hominis as a pathogen at present.>

Has anyone been diagnosed with this particular parasite (I'm not sure which it is)?

Sydney Australia

Date: Fri, 23 Jan 98 12:05:42 CST
From: (Ted Kyle)
Subject: RE: Gottschall and the CCFA


doctors for the most part will only do what the FDA says they should, but the researchers are not totally ignoring the bacteria connection. for example, just recently
Sartor in The American Journal of Gastroenterlogy (1997 Dec;92(12Suppl):5S-11S )
stated the three theories for the etiology of IBD

1) reaction to a presistent intestional infection

2) exsistence of a defective mucosal barrier to luminal antigens

3) a dysregulated host immune respones to ubiquitous antigens

ALL three are related to some kind of bacteria/protozoa/yeast etc ...

in a similar vein Dr Hanauer, Univeristy of Chicago, who "discovered" UC refered a patient to a Dr McCann and this Dr McCann successfully repopulated the patient's bowel with friendly E. Coli strains which caused a four year state of remission. that was reported in 1994, (sadly, nothing more as been published on this technique since.)

so orthodox medicine is coming around, slowly, but not before it's proved to "death".


Arch Biochem Biophys 1994 Nov 15;315(1):161-169

Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers.

By Dinis TC, Maderia VM, Almeida LM

Laboratorio de Bioquimica, Faculdade de Farmacia, Universidade de Coimbra, Portugal.

The action of the phenolic compounds acetaminophen, salicylate, and 5-aminosalicylate (5-ASA) as inhibitors of lipid peroxidation was studied under conditions suitable for establishing their antioxidant potencies. These phenolic compounds react differently with diphenylpicrylhydrazyl (DPPH) and protect differently sarcoplasmic reticulum membranes against lipid peroxidation induced by Fe2+/ascorbate, as evaluated by the formation of thiobarbituric acid-reactive substances (TBARS) and by the loss of the polyunsaturated fatty acyl chains.
5-Aminosalicylate reacts promptly with DPPH, suggesting a potent radical scavenger activity and was found to be the most active in inhibiting Fe2+/ascorbate-induced lipid peroxidation. These compounds also exhibit peroxyl radical scavenging activity generated by the water-soluble 2,2'-azobis-(2-amidinopropane hydrochloride) azoinitiator of peroxyl radicals, as evidenced by the inhibition of cis-parinaric acid fluorescence decay or oxygen consumption.
5-ASA rapidly scavenges peroxyl radicals in the aqueous phase, producing a concentration-dependent inhibition period similar to Trolox or cysteine, suggesting an antioxidant activity of chain-breaking type.
By comparison, the reactivities of acetaminophen and salicylate are significantly weaker, acting essentially as oxidation retardants. Although closely related in structure, the antioxidant efficiencies of the three phenolic compounds are significantly different.
The higher antioxidant activity of 5-ASA is putatively related with the p-amine relative to the hydroxyl group, potentially increasing the stability of the phenoxyl radical.
Such a stabilization is not possible with salicylate and is decreased in acetaminophen by an electron withdrawing effect of the p-acetyl.

PMID: 7979394, UI: 95070159

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