Gluten Sensitivity: A Gastroenterologist's Personal Journey Down the Gluten Rabbit Hole

After publishing two of my earlier articles in the print and electronic version of his popular celiac newsletter ScottFree, Scott Adams the founder of celiac.com, asked me to write an article on gluten sensitivity. The first article of a two part series just published is titled Gluten Sensitivity: A Gastroenterologist’s Personal Journey Down the Gluten Rabbit Hole by Dr. Scot Lewey.

New resources for eosinophilic gut diseases and food allergy, intolerance and toxic reactions I would like to pass on include the American Partnership for Eosinophilic Disorders site and the the extensive All Allergy Net Databases. I also encourage you to subscribe to my online articles and view my video What is the difference between Food Allergies and Food Intolerance?.

As a practicing gastroenterologist I specialize in celiac disease, food allergies, colitis, Crohn's disease, eosinophilic gastrointestinal disease, food intolerance, swallowing disorders, and diagnostic endoscopy including the pill camera.
Join me as I share insights gleaned from my review of the latest research from around the world and experiences with patients in my busy clinical practice in the context of my own personal experience living gluten-free by subscribing to The Food Doc Journal.
Copyright © 2007, The Food Doc, LLC, All Rights Reserved. www.thefooddoc.com

Leaky gut and altered bacteria in gut linked to AIDS. More support for probiotic use?

Leaky gut and bacteria in the gut are important in the progression of AIDS after HIV infection. Benchley et al report elevated levels of lipopolysaccharides (LPS), a component of the cell wall of gram negative bacteria in the gut, in people with AIDS versus those HIV infection without AIDS. Lower levels of LPS therefore less bacterial translocation and leaky gut were observed in people with HIV infection treated with combination anti-viral medications and in monkeys with AIDS like virus who were treated with antibiotics to reduce gut bacteria. Signs of chronic systemic immune activation including severely depleted T-helper type CD4+ white blood cells are associated with HIV progressing to AIDS.

Immune activation in AIDS is then believed the result of the breakdown of the gut mucosal barrier or a leaky gut by HIV infection. Elevated LPS in the blood is a marker of bacterial translocation that is associated with increased gut permeability. Translocation is movement of bacteria or bacteria products through the gut wall without bacteremia or full-blown bacterial blood stream infection. Such increased gut permeability and elevated LPS levels in the blood are linked to inflammatory bowel diseases (IBD) and persistent systemic immune activation probably in part due to bacteria and yeast proteins in Crohn’s disease. The latter is reflected by elevated blood antibodies to Saccharomyces cervesiae yeast (ASCA) and bacteria products (anti-cBir1, OmpC) detected in the blood in many people with Crohn’s disease.

Uncontrolled immune activation in the gut is believed to be central to the abnormal response to food antigens like gluten in celiac disease. The leaky gut from gluten results in development elevated gliadin antibodies and eventually endomysial and tissue transglutaminase antibodies in most people with untreated celiac disease. Since the gut is the primary entrance of most foreign proteins, altered gut barrier followed by chronic persistent immune activation results in more foreign microbes and food protein exposure that promotes further gut injury, i.e. more leaky gut. It becomes a vicious cycle. We cannot change our genes that may predispose us to certain diseases resulting from leaky gut associated foreign protein immune activation but we can control some of our risk for leaky gut.

If you have celiac disease, lactose intolerance, IBD, irritable bowel syndrome or autoimmune diseases you should definitely consider taking a daily probiotic. Avoid medications that injure the gut like NSAIDs (ibuprofen etc.) and antibiotics and acid blockers that may alter gut bacteria levels. Controlling stress as much as possible is important as stress has been shown to increase gut permeability at least in in a rat model. Avoid or limit problem food antigens like gluten and casein or problem food lectins like wheat germ agglutinin, casein, soybean agglutinin, and peanut agglutinin as much as possible. Avoid foods derived from animals or plant sources treated with antibiotics and antifungals. Since avoiding all these factors may be impossible, taking a daily probiotic to restore your gut to healthy levels of microbes makes sense.

References:
Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Benchley JM et al. Nature Medicine 2006; 12:1365-1371.

Gut microbes out of control in HIV infection. Haynes, BF. Nature Medicine 2006; 12: 1351-1352.

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Celiac disease linked to altered gut bacteria: More support for probiotics?

Why celiac disease develops in 1% of people in the world who eat gluten-containing grains but not in the other 35-45% who are genetically at risk is not known. Having abnormal levels of gut bacteria levels is a risk. A 2005 study from Sweden revealed that altered short chain fatty acids (SCFA) levels produced by gut bacteria are a new piece to the puzzle. This also provides further support for the use of probiotics in the treatment and prevention of celiac disease.

The healthy human gastrointestinal tract contains millions of live microbes that aid in digestion and produce various nutrients including SCFAs. These short fragments of fats when unbranched are health food for the intestine. Altered levels of SCFAs are measurable and result from an inbalance of gut microflora. Tjellström et al measured short chain fatty acids levels as an indicator of gut bacteria levels in children with celiac disease and healthy children and found significant differences.

The found both untreated CD and treated CD children had presence of unhealthy longer branched SCFAs. These branched SCFAs cause more intestinal lining cell turnover. This can result in villous atrophy, impaired absorption and an overload of undigested proteins to the distal small bowel and colon resulting in diarrhea. They conclude “our finding may well reflect a deviant gut flora in CD, which may be a new piece in the intriguing puzzle…”

Normal gut bacteria promote healthy gut lining cells thereby preventing a leaky gut by preserving protective intestinal barrier function. Finding altered SCFA levels as a marker of altered gut flora suggests that restoring the normal balance with probiotics could help protect against the development of CD. This concept is supported by other research showing beneficial effects of probiotics in the treatment of colitis, Crohn’s disease, IBS, antibiotic associated diarrhea and HIV/AIDS diarrhea. Maybe we should all be on probiotics.

References:
Gut microflora associated characteristics in children with celiac disease. Tjellström, B, et al. American Journal of Gastroenterology 2005; 100: 2784-2788


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Probiotics, stress and the war on terrorism in the gut

Though it is a rat study I hated during my gastroenterology training, I love a new article by Zareie et al from Toronto published in Gut. Though the link of stress to gut inflammation and bowel diseases is still debated or ignored by many doctors these researchers found probiotics prevented intestinal abnormalities from stress in rats. Their introduction is refreshing as they write “the influence of chronic stress on intestinal dysfunction and clinical outcome of chronic intestinal disorders is recognised…stress is an important risk factor for both development and the reactivation of intestinal inflammation in chronic inflammatory bowel diseases (IBD).”

There are “genetically susceptible rodent models” in whom “chronic psychological stress induces mucosal dysfunction via increased epithelial ion secretion and permeability, enhancing binding of luminal antigens…and initiation of mucosal inflammation.” In other words, rats that are water stressed develop a leaky gut that allows bacteria through the bowel wall (bacterial translocation) that results in intestinal inflammation. This is an accepted inflammatory bowel disease model. However, rats given probiotics consisting of two strains of Lactobacilli bacteria did not experience bacterial translocation effects or bacteria reaching the surrounding lymph nodes.

Though they did not demonstrate elimination of intestinal permeability with the pre-treatment with probiotics, markers of gut barrier dysfunction were improved. Since only two strains of Lactobacilli were used there may have been less of a protective effect of the probiotics because different strains of bacteria (and yeast) produce different beneficial effects on the gut.

Most doctors are skeptical that stress, altered gut flora and food proteins are central to development of gut injury. They rely instead on medications to treat the symptoms and gut inflammation that is already well established. Most of the time this is not particularly effective but instead is often too late to prevent one or more secondary autoimmune diseases. It is possible if not probable that much of this is preventable by dietary changes and probiotics. Does anyone else find the lack of awareness or acceptance of the war on terrorism in our gut frustrating. Is it because someone is waiting for a political solution? It is time to start employng the weapons we have in this battle rather than allow altered gut microorganisms and genetically altered food proteins win.

Reference: Probiotics prevent bacterial translocation and improve barrier function in rats following chronic psychological stress. Zariee, M. et al Gut 206;55:1553-1560.

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Probiotic yeast Saccharomyces boulardii is effective weapon in war against altered gut bacteria terrorism related leaky gut syndrome

Saccharomyces boulardii is probiotic yeast that has been shown effective in the treatment of several diarrheal intestinal illnesses including antibiotic associated diarrhea, travelers diarreha and HIV/AIDS diarrhea. Saccharomyces boulardii has been shown to be effective in preventing relapses of Crohn’s disease and treating pouchitis, a form of intestinal inflammation in surgical pouch created in the treatment of ulcerative colitis. A recent French study provides new insights and hope in the use of probiotics in the treatment of IBD. Functioning like a traffic cop, Saccharomyces boulardii prevents T lymphocyte white blood cells critical to development of Crohn's disease from migrating from lymph nodes surrounding the bowel and thereby prevents colitis in an IBD mouse model.

The effect is curative relative to the amount of the yeast administered. Human studies have confirmed that a steady state of Saccharomyces boulardii is reached in the gut in about 3 days but eliminated within 2-5 days after it is no longer taken orally. Saccharomyces boulardii's inhibitory effect on interferon helps restore gut permeability to normal thereby preventing leaky gut syndrome.

Saccharomyces boulardii yeast was first isolated from lychee and mangosteen fruit in the 1920’s by a French scientist Henri Boulard after observed natives chewing the skin of these fruits to control cholera. Though in the same genus as Saccharomyces cerevisiae (Baker’s, Brewer’s or dietary yeast), Saccharomyces boulardii is not linked to Crohn’s disease or any other disease but its only use is as a probiotic. Elevated levels of antibodies to Saccharomyces cerevisiae (ASCA) are present in about 70% of people with Crohn’s disease, 10-20% with ulcerative colitis, and a few people with celiac disease and cystic fibrosis but rarely in normal people. Increased stool antibody levels have been reported by Enterolab in people who have Crohn's disease ow who are sensitive to dietary yeast and/or gluten.

Bicodex is the largest maker of Saccharomyces boulardii probiotics worldwide. Florastor is the brand name they market Saccharomyces boularii probiotic under in the U.S. while it is marketed under various names such as Ultra-Levure, Interflora, Perenterol in other countrires. The recommended dose varies from one capsule orally daily for prevention of traveler's diarrhea to up to four capsules three times daily for AIDS/HIV associated diarrhea.



A dramatic important shift in the treatment of IBD is reflected in the editorial by Claudio Fiocchi of the Cleveland Clinic published in the same issue as evidenced by his statement “... from a practical standpoint, it makes more sense to take advantage of ‘all’ beneficial properties of probiotics by giving IBD patients combinations of multiple bacteria and yeasts with anti-inflammatory and protective effects, rather than hoping a single probiotics will fight alone and win the battle against an overwhelming and hostile army of gut flora”. The presence of abnormal gut flora is emerging one of the crucial factors in the prevention and treatment of IBD, celiac disease and irritable bowel syndrome. The Food Doc believes it maybe time for all of us to take a daily probiotic in our we fight in the war on terrorism in our gut.

Saccharomyces boulardii inhibits inflammatory bowel disease by trapping T cells in mesenteric lymph nodes. Dalmasso G. et al Gastroenterology 2006; 131:1812-1825.

Probiotics in Inflammatory Bowel Disease: Yet Another Mechanism of Action? Claudio Fiocchi. Gastroenterology 2006 131:2009-2011.
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Blood tests for Crohn's and colitis blood tests and the link of altered gut flora in IBD.

What are Crohn's and colitis blood tests? Currently available blood tests utilized for the diagnosis of Crohn's disease and colitis include pANCA, anti-ASCA, anti-OmpC, and anti-CBir1 flagelin antibodies. Future blood tests will likely include antibodies against certain sugar (mannose) residues that are present in the cell wall of the yeast saccharomyces cerevisiae. Anti-Laminaribioside and anti-Chitiobioside antibodies are present in some Crohn’s patients who are anti-ASCA negative. Such tests will likely help further distinguish people with ulcerative colitis from Crohn's disease, a problem in about 10% of people with IBD.

What is pANCA antibody?
pANCA is peripheral anti-nuclear antibody. It is an antibody to protein in the nucleus of the cell. People with ulcerative colitis develop a positive pANCA frequently though it may be present in some people with Crohn's disease and rarely in normal people. The pANCA antibody has been further divided into subsets by Prometheus Laboratories Inc. Neutrophil-specific pANCA ELISA (NSNA) is positive in the majority of people with ulcerative colitis (UC) and a small subset of people with Crohn’s disease that have disease more like UC. Immunofluorescent cellular staining of neutrophils (NSNA IFA) and enzyme Dnase testing (NSNA DNase sensitivity) is also done as part of the Prometheus IBD Serology 7. When the latter is present in high levels it is significantly associated with development of inflammation of the rectal pouch (pouchitis) created when someone has entire colon removed for ulcerative colitis that does not respond to medical treatment.

What is the ASCA antibody for Crohn’s disease?
ASCA is anti-saccharomyces cerevisiae antibody. Saccharomyces cerevisiae is Brewer’s or Baker’s yeast. Crohn’s patients have high prevalence of increased blood levels of antibody to this yeast. A few people with celiac disease have this antibody present in their blood in the absence of signs of Crohn’s disease.

What is OmpC antibody?
OmpC is the abbreviation for outer membrane C for the antibody to the outer membrane of the Escherechia coli bacteria that develops in many Crohn’s patients though the E. coli bacteria is not thought to be the cause of Crohn’s disease.

What is anti-CBir1 antibody?
Prometheus Laboratories has only recently added this antibody test. It is an antibody to the flagella protein on bacteria that enables movement and attachment of the bacteria in the intestine. When the anti-CBir1 antibody is present in high levels, especially when ASCA and/or OmpC are also present, Crohn’s disease is present. When present at high levels associated with one the pANCA patterns, it is associated with Crohn’s colitis more commonly than ulcerative colitis. It however can be present but not particularly elevated in UC when UC pattern of pANCA is also noted.

How these tests are helpful: If you have a diagnosis of ulcerative colitis or Crohn’s disease these blood tests may be very helpful in your treatment as they predict severity, complications, risks of surgery and response to various treatments. If you have unexplained abdominal pain, diarrhea, blood in your stools then these tests should be considered as if they are all negative then Crohn's disease or ulcerative colitis are unlikely. However, if one or more are present you need a colonoscopy. Since the antibodies detected are primarily against protein products of bacteria and dietary yeast their presence, especially in Crohn's diasease are consistent with the growing belief that altered levels of gut microorganisms or gut flora are critical in teh development of IBD. It also supports the observation that antibiotics and probiotics help many IBD patients and may prevent onset of IBS after gut infection. Stay tuned for more on our journey with the Food Doc.

References:

Abreu MT et al. Use of Serologic Tests in Crohn’s Disease. Clinical Gastroenterology and Hepatology. Vol.4, No. 3. 2001

Dotan I et al. Antibodies Against Laminaribioside and Chitiobioside Are Novel Serologic Markers in Crohn’s Disease. Gastroenterology. Vol.131, No. 2. 2006

Mei, L et al. Familial Expression of Anti-Escherichia coli Outer Membrane Porin C in Relatives of Patients with Crohn’s Disease. Gastroenterology. Vol. 130, No. 4 2006

Stadaert-Vitse et al. Candida albicans Is an Immunogen for Anti-Saccharomyces cerevisiae Antibody Markers of Crohn’s Disease. Gastroenterology. Vol 130, No. 6. 2006

Targan, SR et al. Antibodies to Cbir1 Flagelin Define a Unique Response That Is Associated Independently Crohn’s Disease. Gastroenterology. Vol.128, No.7. 2005

Crohn’s and Colitis Foundation of America (CCFA) www.ccfa.org
Prometheus Laboratories Inc. www.prometheuslabs.com.
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Eosinophilic esophagitis responds better to steroid spray in non-allergic children than in allergic children:Importance of food elimination diet?

Eosinophilic esophagitis EE), also known as allergic esophagitis, may be misdiagnosed as acid reflux in adults and children. Symptoms include choking spells or swallowing difficulties, chest or upper abdominal pain, heartburn not relieved by acid blocker medications, and bouts of vomiting refusal to eat. It is caused allergy blood cells called eosinophils that are not normally present in the esophagus with the exception of relatively few numbers in the lower esophagus in the setting of acid reflux invading the lining of the esophagus or feeding tube, often as a result of food and/or inhaled pollen allergies.

Eosinophils invade the lining of the gut in response to allergic reactions to foods or medications and parasite infections. Once present in the lining they release chemicals in response to foods or other stimuli that can cause swelling, constriction, bleeding, perforation, itching, pain, or scarring of the affected gut.

EE was first described in children but is now being recognized in more adults, especially young men or teenage boys. During an upper endoscopy exam doctors suspect the diagnosis visually by a characteristic appearance of concentric rings that produce a corrugated appearance of the normal smooth tubular esophagus that resembles a cat esophagus termed felinization though some doctors fail to recognize these signs. The lining usually is friable or prone to tear with a “crepe paper” appearance. The diagnosis is confirmed by biopsies that show > or equal to 24 eosinophils per high-powered field.

Constriction or narrowing of the esophagus in EE is common and associated with painful swallowing and bout of food sticking. Trying to “stretch” or dilate this narrowing by a doctor prior to treatment of the underlying inflammation can result in a superficial tear in the esophagus resulting in severe pain or bleeding or worse a full thickness tear or hole requiring surgery.

Foods allergy is commonly associated though not always proved. If you are found to be allergic to food avoidance is recommended as a treatment. Medical treatment is primarily the use of swallowed inhaled nasal steroids. Though swallowed steroid spray usually works, upon discontinuance the condition may return if the allergic foods are not avoided.

A 2006 randomized, double blind, placebo controlled trial of fluticasone propionate spray in children with EE proved a 50% biopsy proven healing compared with only 9% when placebo used. Interestingly, “non-allergic” kids responded best (66% versus 25%). The fact as few as 25% of the allergic did not respond emphasizes the importance of food elimination treatment in the allergic. In another study, a six-food elimination diet was used successfully in children. Be sure to subscribe to the food doc blog so you don’t miss more on the role of food elimination diets in EE and other food related conditions from Dr. Scot Lewey, the Food Allergies Specialist – the Food Doc.
Reference:
A Randomized, Double-Blind, Placebo-Controlled Trial of Fluticasone Propionate for Pediatric Eosinophilic Esophagitis. Konikoff MR et al Gastroenterology 2006;131:1381-1391.
Copyright © 2007, The Food Doc, LLC, All Rights Reserved.
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Dr. Scot Lewey
the food doc
Box 51460
Colorado Springs, CO 80949
Fax 719 320 6000

Leaky gut associated diseases may be helped by taking probiotics

The passage of bacteria, yeast and food toxins through the wall of the leaky gut results in immune activation that is self-perpetuating or autoimmune. The inflammation may occur locally in the gut or in more distant bodily sites such as the joints, skin, and nervous system.

Crohn’s disease, ulcerative colitis, celiac disease and irritable bowel syndrome are all associated with a leaky gut or increased intestinal permeability. Gluten increases gut permeability even in normal intestine. Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) such as Motrin, Advil, Ibuprofen, Aleve, Celebrex, Mobic, and Bextra; steroids like prednisone; and birth control pills are all felt to increase gut permeability.

Alcohol also increases gut permeability. This results in an increase risk of cirrhosis. Toxins produced add to the alcohol injury directly on the liver. Antibiotics are therefore now being advocated to rid the gut of bad bacteria in people with liver disease.

Taking a daily probiotic may be preventive of the more serious effects of increased gut permeability. We will explore the exciting world of probiotics further as we continue our journey into the food-gut health connection. Be sure to subscribe to the food doc blog so you can follow along as I review the latest breakthrough medical research on the link of bacteria and yeast to the leaky gut resulting in bowel inflammation and disease. You may also want to check out a excellent 144 page consumer guidebook on probiotics published in 2005 by one of the modern pioneers in this field Dr. S.K. Dash, Ph.D. See the recommended book link. The book is available through Amazon at the Food Doc aStore.

Copyright © 2007, The Food Doc, LLC, All Rights Reserved.
www.thefooddoc.com
Dr. Scot Lewey
the food doc
Box 51460
Colorado Springs, CO 80949
Fax 719 320 6000

Food Symptom Diet Diary: Importance of Establishing Your Baseline Frequency and Severity of Symptoms

. Food intolerance may be associated with a number of symptoms:
Celiac disease, gluten sensitivity, and other food intolerance may be associated with numerous digestive and non-digestive symptoms. Some of the most common non-digestive symptoms reported by people include fatigue, headaches, bone, joint and muscle pain, mental fogginess, neuropathy, and skin rashes. The most common digestive symptoms include bloating, diarrhea, excess, constipation, heartburn, nausea, vomitting and abdominal pain.

Rating the severity and frequency of common symptoms:
A good place to start when determining if foods are causing your symptoms is to keep a symptom diet diary along with your own “Top Ten Symptoms” list. Before making any change in your diet or eating pattern you should have a medical evaluation and record your baseline symptom, rating each for frequency and severity. With one of my patients I have recently published the HealThySelf Journal that has daily food symptom diary sheets for 3 months and a “Top Ten Symptoms” assessment for each week.

Key to success with an elimination diet is an adequate trial with accurate diary:
When trying to determine if certain foods are contributing to how you feel and the kinds of symptoms you are experiencing, it is important to complete an adequate trial of elimination combined with accurate recording of what you eat and how you feel. A commitment to 4 weeks to try strictly eliminating the foods recommended according to your specific assessment while recording accurately what you are eating and how you feel will help you identify patterns. It will also help you stay motivated to eliminate, restrict or rotate regularly any problem foods especially when you can readily see patterns.

If you are interested in purchasing the HealthySelf Journal send me an e-mail. Online purchasing of this Journal and other helpful products will be available when the premier form of www.thefooddoc.com is launched in the near future. Be sure to subscribe to the food doc blog for more updates.

Copyright © 2006, The Food Doc, LLC, All Rights Reserved.
www.thefooddoc.com
Dr. Scot Lewey
the food doc
Box 51460
Colorado Springs, CO 80949
Fax 719 320 6000

Leaky gut with normal biospsies:Lymphocytic enteritis and TNF

Leaky gut can occur without visible or microscopic signs: Obvious visually apparent defects of the lining of the intestine or mucosa such as ulcerations and erosions or atrophy are associated with increased intestinal permeability but ultra structural studies have shown that areas of the lining can have gaps in the intestinal barrier. Your gut can be leaky though it may look normal during endoscopy. Your gut can be leaky with a normal or minimally abnormal biopsy.

Lymphocytic enteritis is probably the earliest microscopic sign of a leaky gut. This relatively new term refers to biopsy findings of increased intraepithelial lymphocytes without villous atrophy or blunting. Since lymphocytes release chemical mediators such as tumor necrosis factor (TNF) it makes sense that increased numbers of lymphocytes in the villi releasing TNF can result in a leaky gut. With only intraepithelial lymphocytois malabsorption and symptoms can occur. An increase risk of celiac disease and Crohn’s and colitis, especially in genetically predisposed individuals is probably likely, especially if altered gut bacteria and yeast levels are present.

Tumor necrosis factor release results in leaky gut. Anti-tumor necrosis factor (anti-TNF) therapy in the form of remicade (infliximab) and humira (adalimubab) are highly effective in treating Crohn’s disease, rheumatoid arthritis and more recently ulcerative colitis. Unfortunately, such therapy is directed at the an inceased TNF already released, not the underlying cause or predisposition. Be sure to subscribe to the food doc blog for more updates.
Copyright © 2006, The Food Doc, LLC, All Rights Reserved.
www.thefooddoc.com
Dr. Scot Lewey
the food doc
Box 51460
Colorado Springs, CO 80949
Fax 719 320 6000

Leaky gut explained: Part I

Leaky gut syndrome is a term for increased intestinal permeability. The intestine is lined with a single layer of epithelial cells. In the small bowel these epithelial cells are called enterocytes. Enterocytes form the intestinal barrier.

The small intestine lining has projections called villi. The enterocytes of the small intestine have projections on their surfaces known as microvilli where digestive enzymes reside. Intestinal villi and microvilli dramatically increase the absorptive area of the gut. Damage to the enterocytes or their microvilli can affect digestion and absorption.

The enterocytes are joined to each other by tight junctions or zonula occludens that form a barrier to fluid and proteins. The tight juntions may open up the spaces between the cells, the paracellular space allowing movement of intestinal contents inside the body. Abnormally leaky tight junctions result in increase intestinal permeability or a leaky gut. This altered intestinal permeability or barrier function is implicated in several diseases, especially celiac disease and the inflammatory bowel diseases. We will continue to explore these concepts further so be sure to subscribe to the Food Doc blog for automatic updates.

Leaky gut may occur from gluten even in absence of celiac disease

Zonulin levels are increased in celiac disease. However, chronic gluten (gliadin) exposure also affects zonulin in non-celiac intestine. The result is an increased gut permeability (or leaky gut). Just published in Gut is an article reporting abnormal claudin proteins result in patchy loss of barrier function or tight junctions (leaky gut) in active Crohn’s disease. Drago et al published a report in the Scandinavian Journal of Gastroenterology in April 2006 that transient zonulin release could be triggered by exposure to gliadin even in normal intestine. An increase in intestinal permeability was noted in normal intestine though it was not as pronounced as in celiac disease patients. Intestinal tissue from celiac patients, even those in remission, exposed to gliadin demonstated a sustained increase in zonulin release resulting in significant and sustained increased intestinal permeability.

Zonulin affects expression of the proteins claudin and occludin that constitute the cytoskeleton between intestinal epithelial cells that maintain the tight junctions or zonula occludens. There is increasing scientific research indicating that an altered intestinal barrier with increased intestinal permeability is important in the development of celiac disease, inflammatory bowel disease, and possibly even irritable bowel syndrome.

Research is also revealing that altered gut permeability or leaky gut may be present in “normal” people and/or when the intestinal biopsy appears normal. Gluten can trigger this in the intestine of normal people and early celiac disease. When altered gut microflora or dysbiosis (bacteria and/or yeast) in a genetically predisposed person during altered immune states such as during pregnancy, post-pregnancy, surgery, puberty or periods of severe stress, may activate latent celiac disease or trigger inflammatory bowel disease. In some new onset or more severe IBS may develop, especially after a bowel infection such as viral gastroenteritis or dysentery.

Altered gut flora from antibiotics, including those in provided to animals from which we get meat, milk or eggs are also likely contributing as well as our cleaner environment. This effect is becoming known as the hygiene effect that is theorized as possible cause for increasing incidence of Crohn's disease and autoimmune disorders occurring in well developed countries. Co-existing gut injury from non-steroidal anti-inflammatory drugs (NSAID) like ibuprofen, motrin, or advil also appears to be a risk factor. The use of acid blockers, recently reported to increase the risk of osteoporosis, may also adversely impair breakdown of food proteins and predispose to abnormal gut bacterial or yeast levels increasing the risk of gut injury resulting in the leaky gut. For regular updates from this blog subscribe. Forward this blog to friends and family via e-mail by clicking on the letter icon below.

References:
Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Drago, S et al. Scand J Gastroenterol. 2006; 41(4): 408-419

Inflammatory bowel disease: Is it really just another break in the wall? Weber, CR and Turner, JR. Gut 2007; 56(1): 6-8

Changes in expression and distribution of claudin 2,5, and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Zeissig S. et al. Gut 2007; 56(1): 61-72
Copyright © 2006, The Food Doc, LLC, All Rights Reserved.
www.thefooddoc.com
Dr. Scot Lewey
the food doc
Box 51460
Colorado Springs, CO 80949
Fax 719 320 6000

Leaky gut in active Crohn's disease due to altered gut permeability

A just published article in the journal Gut reports abnormal claudin protein levels result in patchy loss of barrier function or tight junctions (leaky gut) in Crohn’s disease. This report highlights the growing importance of gut permeability or leaky gut in Crohn's and colitis as well as celiac disease. In the same issue Dr.’s Weber and Turner write a review that is titled “Inflammatory bowel disease: Is it really just another break in the wall?" that “tight junction permeability is the rate limiting step that defines the overall epithelial permeability". They go on to say that "tight junction defects may be an important source of the overall intestinal barrier defects – that is, permeability increases – seen in patients with IBD.” Finally they add that “Zeissig et al provide strong evidence that the tight junction barrier function is altered in IBD". In a separate online article I review the basics of tight juntions, the proteins zonulin, claudin and occludin and how leaky gut occurs.

It is also becoming clear that certain foods trigger and perpetuate the process of altered gut permeability or leaky gut, probably in the context of altered gut microflora or dysbiosis. Genetic susceptibility, altered immune states and co-existing gut injury. It is apparent that a combination of factors may determine whether someone develops celiac disease, Crohn’s disease or non-celiac, non-IBD leaky gut syndrome with a variety of intestinal and non-intestinal symptoms.

If you have a family history of celiac disease or IBD or are known to carry the high-risk genes for celiac disease or gluten intolerance I believe you should be aggressively evaluated especially if you have any symptoms whether they are gastrointestinal or not. The possibility that gluten or undiagnosed IBD causing symptoms should be considered. Those with symptoms who fail to meet diagnostic criteria for celiac disease or IBD should still consider a trial of a gluten free diet.

Those who have been given a diagnosis of IBS or have unexplained or refractory symptoms GI or not, should consider the possibility of role of food and altered gut flora as a cause before giving up the possibilty that they may be able to feel better or avoid medications that are expensive or cause serious side effects. Subscribe to the Food Doc Blog so you receive automatic updates of my reviews of the latest research on the exciting relationship of food, gut and bacteria in health and disease. Forward this post to friends and family via e-mail by simply clicking on the letter icon below.

References:
Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Drago, S et al. Scand J Gastroenterol. 2006; 41(4): 408-419

Inflammatory bowel disease: Is it really just another break in the wall? Weber, CR and Turner, JR. Gut 2007; 56(1): 6-8

Changes in expression and distribution of claudin 2,5, and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Zeissig S. et al. Gut 2007; 56(1): 61-72
Copyright © 2006, The Food Doc, LLC, All Rights Reserved.
www.thefooddoc.com
Dr. Scot Lewey
the food doc
Box 51460
Colorado Springs, CO 80949
Fax 719 320 6000

Gluten-free casein-free breakfast sausage recommended by the Food Doc

Gluten-free breakfast sausage from Applegate Farms are also casein-free, dairy-free. Three choices include chicken apple, chicken maple and chicken sage sausages that are already cooked. Add gluten-free pancakes or waffles from Bob's Red Mill and you have an old fashioned breakfast that is quite tasty and filling without gluten or casein exposure.

The sausage should be safe for children with autism spectrum disorder on a gluten-free, casein-free diet. Adverse behavior or brain opiate like effects of casomorphin or gluten exorphin are also avoided. Those with celiac disease, cow's milk protein allergy or intolerance and gluten sensitivity may enjoy sausage that is relatively low in fat, high in protein and free of pork.

Applegate Farms has a nice website that provides easy to understand nutritional and food allergy or intolerance information. Their products are organic and pesticide free. Their meat products include gluten-free casein-free hot dogs made from chicken, beef and turkey. If you are looking for a gluten-free and casein-free breakfast sausage or hot dog look for the Applegate Farm label at your local grocer or visit their website at http://www.applegatefarms.com.



As a physician who is gluten sensitive and casein sensitive, the breakfast sausage are a treat that my family and I enjoy a few days a month. Though I restrict my dairy intake because of lactose intolerance and elevated stool casein IgA antibody (Enterolab testing) I have been struggling with going completely casein-free. However, after months of paying close attention to my body I have become convinced that I have symptoms directly related to casein. These include joint stiffness, adult acne like skin eruptions, fatigue, impaired concentration ability, irritability and fatigue that are worse when I do not limit my casein intake.

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Autism linked to cow’s milk protein when GI symptoms present: More thoughts on the brain gut connection.

Though most doctors have been and remain skeptical of a link between autistic behavior and diet many people report improvement of their children’s behavior when wheat and cow’s milk or dairy are avoided. There are quite a number of lay organizations, websites, and articles that advocate a gluten-free and casein-free diet for autism spectrum disorder. Scientific studies that satisfy evidence-based standards of medical experts are very rare. However, studies proving dietary interventions result in a favorable outcome in health and disease are very difficult to design and carry out. An article in 2005 examined the association of immune response to common food proteins in a group of autistic children and found there was a link between cow’s milk protein and autistic behavior when gastrointestinal (GI) symptoms were also present.

Innate immune response was evaluated by measuring the levels of proinflammatory cytokines, chemicals released by white blood cells (WBC) of the body. Both autistic children and children with “non-allergic food hypersensitivity” (NFH) produced higher levels of these chemicals. Only in WBC’s from autistic children with GI symptoms did they find a positive association of these proinflammatory chemicals and cow’s milk protein (CMP).

Casein is the major cow’s milk protein. Besides milk and dairy products it is in many processed foods, medications, cosmetics, margarine, puddings, soups, artificial flavors, protein powders, and canned fish. Casein is also used to manufacture plastics, fabrics, glues and adhesives.

Many parents report a casein-free gluten-free diet increases eye contact, attention, and mood while decreasing aggressive or oppositional behavior, tantrums, and poor attention. Theories for improvement of casein-free diet include improved brain function due to removal of cow’s milk protein by-products that have opiate like effects. Casomorphin is protein fragment or peptide sequence derived from casein that is considered to have an opiate like effect. There are several casomorphins produced by digestion of casein from cow’s milk. People who stop eating wheat and dairy containing foods commonly report withdrawal symptoms. Such effects give new meaning to the term comfort foods and should cause us to pause before offering milk and cookies young children with developing brains and people with neurological or behavioral problems.

The findings of elevated proinflammatory chemicals in autistic children with GI symptoms suggests there is a link between the gut and behavioral symptoms that is immune mediated and related to leaky gut. It has been theorized that milk proteins get into the blood stream through a leaky gut allowing them to reach the rest of the body resulting in skin rashes, bone and joint inflammation of pain, and disturbed brain function. More research is needed in this area but trials of dairy free diet (and gluten-free diet) have been received with great support from many individuals who note improvements in their symptoms and overall health.

Reference:
Dysregulated innate immune responses in young children with autism spectrum disorders. Their relationship to gastrointestinal symptoms and dietary interventions. H. Jyonouchi, Lee Geng, Agnes Ruby, Barbie Zimmerman-Bier. Neuropsychobiology. 2005;51:77-55.

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