Lymphocytes, eosinophils and mast cells: What your "normal" appearing gut lining may be hiding under the microscope can be missed.

Thousands of people are undergoing endoscopic exams daily without having any biopsies performed though they have symptoms. Sadly, though their exams may visually appear normal, under the microscope may likely be microscopic findings that explain their symptoms. These findings also may direct a therapy that will relieve their symptoms. The gut is lined with larger cells that have in their tips a few immune cells. These immune cells, or lymphocytes, release chemical mediators that fight off infection and attract other cells to the area join the fight to protect the border of the gut from foreign invaders.

Lymphocytes are the primary immune cells normally present in small numbers in the surface cells of the gastrointestinal tract but in certain conditions they may be joined by eosinophils and mast cells. A few lymphocytes are present in the tips of the surface cells that are a type of epithelial cell. These lymphocytes act as the body’s scouts. They survey the barrier of the gut to the inside of the body, looking for signs of potential invading infectious agents. Once an attack is perceived, they signal reinforcements to join them on the front lines.

When persistent increased numbers of lymphocytes are present in the surface cells, a chronic inflammatory condition of the gut exists. In the duodenum, autoimmune reaction to gluten in genetically susceptible individuals is a common but frequently missed cause of chronic inflammation known more commonly as celiac disease or Sprue.

Eosinophils and mast cells are types of immune cells involved in allergy reactions in the body. They are less commonly present in the gastrointestinal lining except when there are parasites, food allergies, or chronic inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis. Eosinophilic gastrointestinal disorders are less common and a newly recognized condition, mastocytic enterocolitis, is diagnosed when excess mast cells are present in the small bowel and colon. However, mast cells may be difficult to see on biopsies without a special stain for tryptase, an enzyme present in mast cells that are immunologically activated.

The esophagus normally contains no eosinophils. The two exceptions gastroesophageal acid reflux in which small numbers, up to 6-7 usually and no more than 10-12 per high power field (40X magnification) are found in the lower esophagus only not in the mid or upper esophagus. Allergic eosinophilic esophagitis is diagnosed when 15 or more eosinophils per high power field are found in more than two fields or more than 20 to 24 per high power field in one field are seen or lesser numbers are present in the upper esophagus. Mast cells that are activated have also been found associated with allergic eosinophilic esophagitis and their presence supports allergic esophagitis over reflux as the cause of the increase eosinophils though it is believed some people have both conditions coexisting.

In the stomach and small intestine more than 10 eosinophils per high power field defines eosinophilic gastroenteritis. In the small intestine and colon more than 20 mast cells per high power field found in association with otherwise unexplained diarrhea is now termed mastocytic enterocolitis. This newly recognized and described entity is previously unrecognized cause of diarrhea in some patients diagnosed with irritable bowel syndrome who may have been told they have a normal colon exam though no biopsies were done. Similarly, more than 20 lymphocytes per 100 epithelial cells in the colon are found in lymphocytic colitis, another form of microscopic inflammation of the intestine resulting in diarrhea that may be inappropriately diagnosed as IBS.

In many of these patients, gluten sensitivity is to blame and the lymphocytic colitis is felt to represent a colonic form of celiac disease. In celiac disease, 30 or more lymphocytes in the tips of the villi per 100 epithelial cells is the earliest sign of gluten injury occurring before the villi become flattened or blunted. This finding may noted before the specific blood tests, anti-endomysial (EMA) and anti-tissue transglutaminase (tTG) antibodies appear in the blood even though the intestine is damaged enough to result in nutrient malabsorption and diarrhea. Anti-gliadin antibodies are often present however when significant intra-epithelial lymphocytosis is present along with symptoms that respond to gluten free diet. Lesser degrees of intra-epithelial lymphocytosis have been proposed as highly suggestive of early celiac disease and or gluten sensitivity, in the range of 20-25 per 100 epithelial cells.

In the colon, the presence of eosinophils is considered one of the earliest findings of chronic inflammatory bowel disease. In the right colon more than 20 eosinophils per high power field and in the left colon greater than 20 per high power field is considered abnormal and suggests eosinophilic colitis, chronic inflammatory bowel disease or a parasitic infection.

Eosinophils and mast cells release chemicals that irritate the bowel, increase permeability (cause leaky gut), increase contractions of the gut, increase intestinal secretions and heighten pain. Both cells are related to allergies including food allergies. It is therefore not difficult to conceive of a link to adverse food reactions in the development of intestinal irritation.

The important point to be aware of if you have gastrointestinal symptoms and are undergoing or have undergone an endoscopic examination is that a normal appearing intestinal lining does not exclude the presence of damage or irritation sufficient to cause symptoms of pain, bloating, gas, and diarrhea nor exclude impaired digestion and absorption.

Only through obtaining tissue samples that are examined under the microscope can abnormal types and number of inflammatory cells be identified. It is through biopsies of normal appearing intestinal lining that the correct diagnosis of various microscopic forms of gastrointestinal inflammatory diseases is confirmed. So, if you are preparing to undergo an endoscopic exam, I encourage you to insist that your doctor perform biopsies even if your exam is visually normal. Based on the information I have reviewed above, a normal exam should be tip off that one of these microscopic conditions might be to blame for your symptoms.

Copyright © 2007, The Food Doc, LLC, All Rights Reserved.
www.thefooddoc.com


References:

Al-Haddad S and Ridell RH. “The role of eosinophils in inflammatory bowel disease.” Gut 2005; 54:1674-1675.

Guilarte M et al. “Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum.” Gut 2007;56:203-209.

Jakarte S et al. “Mastocytic enterocolitis. Increased mucosal mast cells in chronic intractable diarrhea.” Arch Pathol Lab Med. 2006;130:362-367.

Kirsch R et al. “Activated mucosal mast cells differentiate eosinophilic (allergic) esophagitis from gastroesophageal reflux disease.” Journal of Pediatric Gastroenterology and Nutrition 2007;44:20-26.

Liacouras CA. “Eosinophilic gastrointestinal disorders.” Practical Gastroenterology March 2007. 53-67.

Rubio CA et al. “Lymphocytic esophagitis: a histologic subset of chronic esophagitis.” Am J Clin Pathol. 2006;125(3):432-437.

Yousef MM et al. “Duodenal intraepithelial lymphocytes in disorders of the esophagus and stomach.” Clinical Gastroenterology and Hepatology 2006;4:631-634.

Food, bacteria, yeast & the leaky gut meet probiotics & gluten free diet in the fight against Crohn's disease and Celiac

Food, bacteria and yeast in the gut are increasingly being acknowledged by doctors to have a role in the development of a variety of chronic diseases. For years alternative and complementary health practitioners have been advocating various elimination diets and supplements for treatment of a myriad of illnesses and symptoms. Recently more medical researchers are seriously looking into science of food and gut bacteria and yeast causing illness. This research is more common in Europe than in the West because in the U.S. most of the research funding is linked to drug development. Since dietary treatment is not a drug pharmaceutical companies are generally not interested. Their deep pockets are not available to the research scientists working on food related illness who depend on pharmaceutical company funds to survive in academic medicine.

However, Celiac disease affects 1%, food allergies 8%, gluten sensitivity 10% and various food intolerance 30-60%, so what we eat is important. Our genetics play an important role as well. Between 35-45% of people are genetically at risk to develop Celiac disease. Many of these people are gluten sensitive. The majority of people with Crohn’s disease have detectable antibodies in their blood to a variety of proteins that come from bacteria and common dietary yeast. It is believed that these proteins trigger abnormal immune responses in the gut in genetically predisposed people.

Around seventy percent of people with Crohn’s disease have elevated levels of antibodies to the dietary yeast Saccharomyces cerevisiae,more commonly known as Baker's or Brewer's yeast. These anti-Saccharomyces cerevisiae (ASCA) antibodies are rarely present in blood in people without Crohn’s but may be detectable in the stool in people sensitive to dietary yeast. Though touted as very sensitive and specific for Crohn's disease and rarely present in blood in normal people, ASCA antibodies can be detectable in other digestive conditions including Celiac disease.

I have found many of my Celiac disease, non-celiac gluten sensitive, and various microscopic colitis (lymphocytic, collagenous, eosinophilic and mastocytic enterocolitis) patients have detectable to elevated ASCA levels. Often they are combined with other antibodies to intestinal bacteria and food proteins. Gut bacteria proteins from the outer membrane protein (OmpC) and flagella (CBir1) of certain bacteria are also present in many Crohn’s patients. Antibodies to the toxic protein gliadin produced from wheat gluten digestion are often detectable. The specific antibodies for Celiac disease, endomysial (EMA) and tissue transglutaminase (tTG), are by definition only detectable in the blood in Celiac disease. However, gliadin and tTG antibodies are usually present in the stool in people sensitive to gluten and are always present in untreated Celiac disease.

As a gastroenterologist who specializes in Crohn’s, colitis, Celiac disease, gluten sensitivity and various food allergies and intolerance, I test as many of my patients as possible for these antibodies. I find many patients with gastrointestinal symptoms who fail to meet the strict diagnostic criteria for Crohn’s disease, ulcerative colitis or Celiac disease have detectable levels of antibodies to these proteins in their blood or stool. Not all people with detectable ASCA antibodies have Crohn’s disease. Often, though they have digestive symptoms, I am unable to definitely diagnose Crohn’s disease by colonoscopic biopsies of the intestine or wireless capsule endoscopy (the swallowed pill camera). However, most respond to standard medications used to treat Crohn’s disease and colitis.

Even more interesting is that many also respond to probiotics and elimination diets, especially the gluten free diet. I believe some of these people have very early Crohn’s while others have various forms of increased gut permeability or leaky gut but have not yet developed irreversible Crohn's disease or other chronic intestinal dieases. Because I believe altered gut bacteria or dysbiosis is a critical factor in the development of abnormal intestinal permeability or leaky gut leading I recommend a probiotic. For those who I believe have severely altered gut bacteria or yeast (dysbiosis), I may first prescribe a course of an antibiotic or an anti-fungal medication. Though there are many probiotics available, I prefer the probiotic bacteria preparations VSL#3, Ultimate Flora, and Flora Q, based on their large numbers of multiple strains of good gut bacteria and absence of gluten.
In patients with elevated ASCA, Crohn’s disease, antibiotic associated diarrhea, or C. difficile infection, I frequently now recommend the probiotic yeast Saccharomyces boulardii.


With these new antibody tests and the recognition that the gut can be irritated at the microscopic level when it appears normal is resulting in the ability to detect earlier signs of gut injury. Such injury results in increase permeability or leaky gut resulting in the ability of food and gut bacteria and yeast proteins tranlocating or moving through the intestine wall. Once these foreign proteins get through the gut wall they encounter white blood cells that especially in the genetically predisposed can activate an self perpetuating abnormal immune activation response and gut inflammation leading to more gut injury. The resulting further leaky gut can allow more foreign proteins to get access into the blood stream where they can travel to other parts of the body and cause injury and a host of other non-digestive symptoms.

As the result of these antibody tests to food, bacteria and yeast proteins combined with microscopic examination of the gut we are identifying more people with symptoms that may respond to treatment before they have enough damage to establish a definitive diagnosis of Crohn’s disease, ulcerative colitis, or Celiac disease. Some have various forms of microscopic enterocolitis, intestinal conditions where the surface appears to be normal visually but under the microscope there inflammation or irritation indicating an abnormal response to food, bacteria and yeast.

I am preparing a presentation on nutrition in inflammatory bowel disease I was invited to give at a conference for Crohn’s and colitis patients and their families sponsored by the Rocky Mountain Chapter of Crohn’s and Colitis Foundation of America (CCFA). I wanted to share some of my thoughts with those following my blog that has had to take a brief hiatus due to family health issues. See my Food Journal Report post tomorrow about neurological symptoms and possible link of herniated discs to Celiac disease and gluten. To your "Healthy Gut, Healthy Life", the Food Doc.

Copyright © 2007, The Food Doc, LLC, All Rights Reserved.
www.thefooddoc.com

Blocking Wheat Gluten Toxicity With Digestive Enzyme Pill Might Have Prevented My Wife's Neurological Symptoms From Accidental Gluten Exposure

Taking a pill to allow eating gluten is a very appealing idea to people suffering from Celiac disease. Trying to maintain a gluten free diet for life, especially while traveling or having an active social life is nearly impossible. However, for those with Celiac disease, gluten exposure can cause serious symptoms and increase the risk of numerous cancers, especially lymphoma. It is unlikely a pill will become available in the very near future that would allow an unrestricted diet. However, in the February 2007 issue of the journal Gut, Dr. Cerf-Bensussan et al. from France, review the latest research that has progressed to the early stages of developing a gluten digestive enzyme pill. Oral proteases, enzymes that break down proteins, are being developed that target the toxic wheat gluten protein product gliadin that causes Celiac disease.

A pill combining two or more of these digestive enzymes may allow people with Celiac disease and gluten sensitivity to eat gluten occasionally during social events or during travel as well as protect against the exposure to hidden sources of gluten. After my wife and I got accidentally “ glutened” during a trip to visit family I was very interested to review this update. I experienced more minor nuisances from the gluten exposure such as acne like skin break outs, joint stiffness, muscle aches, impaired concentration and moderate fatigue. However, my wife who has Celiac disease and is extremely sensitive to hidden gluten, suffered from two days of incapacitating fatigue and a flare of neurological symptoms. While traveling back from our trip I had to assist her to walk because she developed such acute and profound muscle weakness, incoordination and balance difficulties, not to mention the inability to think or speak clearly for the past 24-48 hours.

To those unfamiliar with the toxic effects of gluten on the neurological system, including most of my physician colleagues (even neurologists and gastroenterologists here in the U.S.) it is hard to believe that getting exposed to minute amounts of wheat, flour or gluten can cause these profound symptoms. However, for those of us who have experienced this first hand as a sufferer of Celiac disease, family member of those affected by gluten sensitivity or in my case a doctor who specializes in Celiac disease and gluten sensitivity, who also is gluten sensitive and married to a Celiac, it is not surprising. Instead it can be maddening to see the lack of awareness, sensitivity and general disbelief of the medical establishment to the toxic effects of gluten on the body. The resistance to the idea that eating wheat may not be healthy is great in the U.S. Sadly it has taken to death of hundreds of cats and dogs to raise the public awareness to wheat gluten, though the cause of the illness in those pets appears to be due to the contaminant melamine. However, I would advise people to remain open to the possibility the gluten may have also played a role. This is based on my experience with humans suffering serious illness due to gluten and the research I have found on toxicity of gluten in animals.

A heightened awareness to the potential dangers of gluten is coming from all the recent media attention to the pet food contamination. In the meantime, those of us with gluten sensitivity and Celiac disease can hope for a pill in the near future that can be taken to break down toxic gluten before ill effects develop. I will follow up this posting with more details but I wanted to share our story and provide the article reference to those of you following along with my journey of a “healthy gut, healthy life”. Upon return from being out of town I found the Food Doc Twinkie Experiment revealed 26 days has still failed to result in any mold or visible deterioration. Stay tuned for more exciting news on Celiac disease, eosinophilic esophagitis, IBS, Crohn’s disease, leaky gut, probiotics and the links to food and microorganisms. I have more than a dozen articles to share with you.

the Food Doc, Dr. Scot Lewey.

Copyright © 2007, The Food Doc, LLC, All Rights Reserved.
www.thefooddoc.com

Reference:
Cer-Bensussan N. et al. "Oral proteases: a new approach to managing coeliac disease" Gut 2007; 56:157-160.