IBS vs. IBD and other tummy aches.

CONTINUING EDUCATION

To earn CEUs, see test on page 20.

LEARNING OBJECTIVES

Upon completion of this article, the reader will be able to:

1. Identify inflammatory bowel disease (IBD) based upon clinical presentation as well as data obtained through laboratory analysis.

2. Differentiate between genetic contributions and environmental influences with respect to disease processes.

3. Identify irritable syndrome (IBS) based upon clinical presentation as well as data obtained through laboratory analysis.

4. Compare and contrast IBD and IBS.

5. Describe the clinical and laboratory relevance of the autoantibodies associated with celiac disease.

6. Recognize potential patient complications due to gluten sensitivity enteropathy.

7. Identify the relationship between celiac disease and thyroid disorders.

8. Describe the pathology of leaky gut syndrome and suggest appropriate treatment modalities.

9. Identify atrophic gastritis based upon clinical presentation as well as data obtained through laboratory analysis.

10. Differentiate between the two causes of atrophic gastritis.

11. Correlate pernicious anemia with autoimmune atrophic gastritis.

**********

Although they cause similar symptoms, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are different conditions with different courses, different treatment options, and different outcomes. These disorders may also be confused with celiac disease and other enteropathies. The clinical laboratory plays an important role in differentiating these disorders.

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Diagnosing IBS

According to the International Foundation for Functional Gastrointestinal Disorders (www.iffgd.org), irritable bowel syndrome (IBS) is second only to the common cold as a cause of absenteeism from work. It is also the disorder most commonly diagnosed by gastroenterologists, and one of the top 10 most frequently diagnosed conditions by U.S. physicians.

IBS is a common functional gastrointestinal disorder that causes increased contractions or spasms of the colon or rectum. In IBS patients, the colon is more sensitive and contracts more readily than it does in other people. IBS is a syndrome or collection of symptoms rather than a disease; it is not an inflammatory disorder.

Symptoms of IBS include chronic abdominal pain, discomfort, diarrhea, and constipation, and often occur in people with systemic lupus erythematosus, fibromyalgia, and other disorders. In these conditions, IBS symptoms are often linked to stress, inadequate fluids, poor nutrition, and poor eating habits (i.e., eating too fast or not relaxing after a meal).

IBS is diagnosed in people having symptoms for at least 12 weeks in the preceding 12 months. An examination of the colons of IBS patients may show no significant changes; however, two of the following features must be present for a diagnosis of IBS:

* relief upon defecation;

* onset associated with a change in frequency of stool; and

* onset associated with a change in form of stool.

Imaging tests and blood tests are used to rule out the presence of other disorders (e.g., celiac disease, lactose intolerance, and food allergies) that may mimic IBS.

Diagnosing IBD

On the other hand, inflammatory bowel disease (IBD) is chronic, autoimmune, and inflammatory; it may also be called colitis, enteritis, ileitis, and proctitis. IBD, however, refers mainly to two autoimmune disorders--Crohn's disease and ulcerative colitis--both of which lead to gastrointestinal distress pain and inflammation, and both of which can lead to the development of fistulas. (Lesions in Crohn's disease involve the presence of strictures, abscesses, and fistulas.) Together, these two disorders affect about one in every 1,000 people, but recent studies indicate that this number is on the rise.

Crohn's disease may involve any part of the intestine, including the colon. Often, the entire bowel wall is involved. Unlike ulcerative colitis, which primarily involves the mucosal lining of the colon, in Crohn's, some parts of the intestine are affected while adjacent areas remain unscathed.

Ulcerative colitis typically affects the rectum and spreads toward the proximal colon, although the entire colon is affected in some patients. In others, disease is restricted to the lower areas of the bowel. Like most autoimmune disorders, periods of symptoms tend to alternate with periods of remission. This disease also is associated with an increased risk of colon cancer, particularly in those patients with extensive colitis of long duration.

Patients with inflammatory bowel disease have symptoms of diarrhea; abdominal pain, usually on the right side of the lower abdomen; fever; a feeling of a mass or fullness in the lower, right abdomen; weight loss; and bloody stools.

Perinuclear antineutrophil cytoplasmic antibodies, or P-ANCA, are seen in IBD, and inflammatory white blood cells are seen in the colon mucosa. On occasion, signs and symptoms of both Crohn's disease and ulcerative colitis cause an overlapping type of inflammatory bowel disease. Many physicians think that symptoms of IBS can occur in patients with IBD. (1) Doctors have already ascertained that patients with IBD often complain of having symptoms of IBS for several years before being diagnosed with IBD. Studies show that people with IBS do not have a higher risk of developing IBD than other people; however, patients diagnosed later in life with IBD tend to have had a history of IBS symptoms prior to diagnosis. (1)

Who suffers?

IBS affects at least 10% to 20% of adults in the United States--two-thirds of all cases occur in women (2) while up to 600,000 Americans are reported to suffer with IBD. (3) Both strike primarily in young people in their teens, 20s, and 30s. Although mortality is low, IBD can cause significant episodes of disease activity with the potential to cause frequent hospital admissions, chronic ill health, persistent infections, altered development, poor quality of life, and a decreased sense of social assuredness. The greatest chance for complications and related development problems occurs in the youngest patients for whom developmental problems are common.

A recent study conducted at Boston University (4) showed that up to 40% of IBS patients suffer from depression related to changes in serotonin levels. Low serotonin levels in IBS patients stem from gastrointestinal influences affecting serotonin production and release. (According to researchers, up to 95% of the body's supply of serotonin is found in the colon.) Similar studies have shown an increased rate of depression in IBD patients. In a large study conducted in Italy, researchers showed that the overall severity of psychological symptoms was not statistically different between patients suffering from IBS vs. IBD. (5)

What do we know?

For many years, IBD diagnosis and treatment advances have been lacking. The tide has turned, however, and recently, we have seen progress in IBD include the development of molecular-based diagnostic tests and emerging biologic treatments. Molecular-genetics testing shows that people with IBD have distinct genetic markers, with independently replicated loci designated as IBD1 through IBD5. (6)

Furthermore, genetic studies show that Crohn's disease and ulcerative colitis share some, but not all, of a limited set of disease-susceptibility genes. From a genetic standpoint, IBD stands alone among complex genetic diseases because of these five confirmed susceptibility loci. In recent years, the responsible gene for IBD--NOD2--has been located on chromosome 16. This gene highly suggests that a defective immune response to enteric bacteria is the underlying cause of IBD. Specifically, the immune system in IBD patients fails to respond properly to the lipopolysaccharides of enteric bacteria. (7)

European hereditary studies show that IBD is much more likely to develop in families with a history of IBD, especially when a first-degree or second-degree relative is affected. Between 6% and 32% of IBD patients have such a relative, with a greater association seen in Crohn's disease. A strong familial association also influences age of onset, disease location, extra-intestinal (other than gastrointestinal) symptoms, and a tendency to form fistulas (fistulizing pathology). (6)

The degree of genetic contribution to IBD also follows ethnic lines. For instance, studies show that Jewish patients in both Cleveland and Los Angeles had a higher likelihood of developing IBD than non-Jewish patients in these locales. Studies also suggest that immune-system genes--for instance, the tumor necrosis factor-alpha gene--also influence disease development and progression. Overall, genetic susceptibility appears to be the greatest risk factor for developing IBD. (7,8)

Like other autoimmune disorders, IBD is also associated with environmental factors that influence disease susceptibility, progression, and the variability seen in symptoms and their severity. Environmental agents known to have triggered IBD development include antibiotics, analgesics (e.g., aspirin and ibuprofen); gastrointestinal infection with various viruses and bacteria, including Klebsiella and Yersinia; and toxic proteins in wheat, rye, and barley. Gluten sensitivity (see sidebar on page 13) is also thought to be a contributing factor in the development of IBD. Smoking has been found to influence IBD development, with IBD being twice as likely to be found in smokers as in non-smokers. According to researchers, smoking is the only established risk factor in Crohn's disease and smoking cessation in ulcerative colitis patients improves their disease symptoms. (9)

What about progression?

Studies of animal models with IBD symptoms have provided valuable clues regarding disease progression. For instance, immune-system chemicals known as cytokines released during the misdirected immune response contribute to the chronic inflammation seen in IBD patients. These studies have led to various treatments. For example, infliximab (Remicade) was introduced as a treatment to reduce levels of inflammatory cytokines such as tumor necrosis factor-alpha. About one-third of IBD patients, however, do not respond favorably to infliximab. Ongoing studies of various types focusing on the immune mechanism in IBD development will undoubtedly provide further insights into effective treatment modalities. (10)

Elaine Moore, BSMT/Chemistry, is a medical technologist, medical writer, Graves disease patient, and patient advocate with more than 30 years' experience working in hospital laboratories. Currently, Moore is the night supervisor on the "graveyard" shift at Memorial Hospital in Colorado Springs, CO. She wrote all of the material for the three sidebars in this cover article.

References

1. Burgman T, Clara I, Graf L, et al. The Manitoba Inflammatory Bowel Disease Cohort Study: Prolonged symptoms before diagnosis--how much is irritable bowel syndrome? Clin Gastroenterol Hepatol. May 2006; 4(5):614-620.

2. Jones S. Beat the IBS Blues. Natural Health. April 2007:18.

3. Staros EB. Molecular Discoveries Alter Our View of Inflammatory Bowel Disease, Medscape, 5/12/02. Am J Clinc Pathol. 2003;119(4):524-539

4. Cole JA, Rothman KJ, Cabral HJ, Zhang Y, Farraye FA. Migraine, fibromyalgia, and depression among people with IBS: a prevalence study. BMC Gastroenterology. 2006;6:26.

5. Pace F, Molteni P, Bollani S, et al. Dept. of Gastroenterology, Milan, Italy: Inflammatory bowel disease vs. irritable bowel syndrome: a hospital-based, case-control study of disease impact on quality of life. Scand J Gastroenterol. October 2003;38(10):1031-1038.

6. Keren D, Goeken J. Autoimmune Reactivity in Inflammatory Bowel Diseases, Progress and Controversies in Autoimmune Disease Testing, Clinics in Laboratory Medicine, Philadelphia: W.B. Saunders Company, September 1997:465-481.

7. Staros EB. Inflammatory Bowel Disease: A Genomic Picture Predicts a Changing Response from the Laboratory--Part II. Laboratory Medicine. May 2003.

8. Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. J Clin Invest. 2007;117:514-521.

9. Bernstein C, Rawsthorne P, Cheang M, Blanchard J. A Population-Based Case Control Study of Potential Risk Factors for IBD. Am J Gastroenterol. 2006;101(5):993-1002.

10. Sellin J. Why Treatment Fails in IBD. Available at: http://www.intmed.utmb.edu/grandrounds/IBD. Accessed March 23, 2007.

CE test on IBS VS. IBD AND OTHER TUMMY ACHES

MLO and Northern Illinois University (NIU), DeKalb, IL, are co-sponsors in offering continuing education units (CEUs) for this issue's article on IBS VS. IBD AND OTHER TUMMY ACHES. CEUs or contact hours are granted by the College of Health and Human Sciences at NIU, which has been approved as a provider of continuing education programs in the clinical laboratory sciences by the ASCLS P.A.C.E.[R] program (Provider No. 0001) and by the American Medical Technologists Institute for Education (Provider No. 121019; Registry No. 0061). Approval as a provider of continuing education programs has been granted by the state of Florida (Provider No. JP0000496), and for licensed clinical laboratory scientists and personnel in the state of California (Provider No. 351). Continuing education credits awarded for successful completion of this test are acceptable for the ASCP Board of Registry Continuing Competence Recognition Program. After reading the article on page 10, answer the following test questions and send your completed test form to NIU along with the nominal fee of $20. Readers who pass the test successfully (scoring 70% or higher) will receive a certificate for 1 contact hour of P.A.C.E.[R] credit. Participants should allow four to six weeks for receipt of certificates.

The fee for this continuing education test is $20.

All feature articles published in MLO are peer-reviewed.

Learning Objectives and CE test questions were prepared by Jennifer A. Lichamer, MT(ASCP), and reviewed by Jeanne M. Isabel, MSEd, CLSpH(NCA), MT(ASCP), associate professor, School of Allied Health Professions, College of Health and Human Sciences, Northern Illinois University, DeKalb, IL.

1. The greatest chance for complications due to irritable bowel disease (IBD) occurs in older female patients.

a. TRUE

b. FALSE

2. The gene responsible for IBD is

a. IBD1.

b. IBD2.

c. NOD1.

d. NOD2.

3. Chronic inflammation due to IBD can be attributed to

a. TNF alpha.

b. cytokine release.

c. Eosinohilia.

d. Both a and b.

4. Ulcerative colitis is associated with an increased risk of colon cancer.

a. TRUE

b. FALSE

5. What percentage of Americans reportedly suffer from irritable bowel syndrome (IBS)?

a. 10%

b. 15%

c. 30%

d. 35%

6. IBS can be classified as a disease.

a. TRUE

b. FALSE

7. IBS patients may suffer depression due to low levels of

a. serotonin.

b. calcium.

c. vitamin D.

d. insulin.

8. Which of the following antibodies is not associated with celiac disease?

a. IgG antigliadin antibodies

b. IgM antigliadin antibodies

c. Endomysial antibodies

d. Tissue transglutaminase antibodies

9. People with celiac disease ______ intestinal B-lymphocytes.

a. over produce

b. under produce

c. never produce

10. Patients presenting with gluten sensitivities commonly express any of the following conditions except

a. delayed puberty.

b. Turner's syndrome.

c. Factor IV Leyden.

d. iron deficiency anemia.

11. Asymptomatic individuals with celiac disease express all but which of the following conditions?

a. Villous atrophy

b. Lymphocytosis 

c. Cervical hypertrophy 

d. Crypt hyperplasia

12. The most common HLA genotype in patients with celiac disease is

a. DQ2

b. DQ3

c. DQ8

d. DQ13

13. It is safe for patients with gluten sensitivities to ingest gluten in amounts as low as 0.1 grams without experiencing changes in intestinal tissue.

a. TRUE

b. FALSE

14. Malabsorption describes a defective digestive process causing poor absorption of water-soluble substances.

a. TRUE

b. FALSE

15. Which of the following statements does not describe celiac disease?

a. It develops later in life.

b. It is often not diagnosed when symptoms are vague.

c. It is always diagnosed regardless of the strength of the symptoms.

d. It often occurs in patients with thyroid disease.

16. In leaky gut syndrome, chronic inflammation from ______ is not known to damage the body's protective coat of IgA.

a. thyroid hormones

b. alcohol

17. Probiotics are often utilized to treat IBS.

a. TRUE

b. FALSE

18. The greatest risk factor for developing IBD is

a. genetic susceptibility.

b. environmental susceptibility.

c. antibiotics

d. caffeine

19. The inability of the stomach lining to absorb protein molecules is seen in

a. leaky gut syndrome.

b. intestinal permeability.

c. celiac disease.

d. Both a and b.

20. Which of the following conditions is known to affect the stomach's mucosal lining?

a. Vitamin B12 deficiency 

b. Atrophic gastritis

c. Irritable bowel syndrome

d. Inflammatory bowel disease

21. Atrophic gastritis associated with Helicobacter pylori

a. tissue destruction is restricted to the gastric corpus and fundus.

b. is a multi-focal process.

c. is likely to lead to the development of stomach cancer.

d. autoantibodies cause destruction of the parietal cells.

22. Which of the following conditions does not have symptoms related to those observed in autoimmune atrophic gastritis?

a. Megaloblastic anemia

b. Thrombocytopenia 

c. Cobalmin deficiency

d. Hashimoto's thyroiditis

23. Patients with gastric adenocarcinoma are approximately three times more likely to have pernicious anemia than are the general population.

a. TRUE

b. FALSE

24. What percentage of Americans suffer with atrophic gastritis?

a. The frequency is not known.

b. 5%

c. 8%

d. 10%

25. Atrophic gastritis affects men three times as often as women.

a. TRUE

b. FALSE

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By Elaine Moore, BSMT 

RELATED ARTICLE: Celiac disease: gluten sensitivity enteropathy

Gluten is a fraction of wheat flour, which is composed of two groups of proteins: the glutenins and the gliadins. Individuals with celiac disease are intolerant to the gliadin fraction of gluten and to equivalent proteins found in wheat, rye, and barley. Recent studies show that in North America and Europe the risk for celiac disease--also known as gluten sensitivity enteropathy or GSE--ranges from 0.4% to 1% or about one in every 250 people. (1) Celiac disease, celiac sprue, and non-tropical sprue affect one in every 133 Americans. (1) The only treatment for celiac disease is adherence to a gluten-free diet. Previous studies have shown that patients with celiac disease who continue to ingest the gluten protein found in wheat, rye, and barley have increased levels of TSH receptor antibodies as well as increased levels of the gliadin and endomysial antibodies typically seen in celiac disease. (2)

Because gluten sensitivity reaction is immune-mediated, it is one in which the environmental trigger is clearly known. Gluten sensitivity develops in those people with immune-system genes (HLA antigens) that predispose them to disease development. Such sensitivity develops in varying degrees with people experiencing mild gastrointestinal symptoms after ingesting wheat products, to people with symptoms of overt intestinal damage to the microvilli and frank celiac disease. Untreated, the immune changes caused by celiac disease can lead to intestinal malignancies, lymphomas, and other morbidities.

Even in the absence of symptoms, individuals with celiac disease who continue to ingest gluten develop changes in their small intestines including villous atrophy, destruction of the intestinal villi that absorb nutrients; invasion of the gastrointestinal tract by lymphocyte white blood cells; and crypt hyperplasia, a form of cellular overgrowth. Intestinal symptoms include abdominal pain, distension, bloating, vomiting, and diarrhea. (1)

While the intestines are primarily affected, celiac disease also causes systemic changes affecting the skin, liver, bones, joints, heart, brain, and other organs. Long-term complications of untreated celiac disease include osteoporosis, increased risk of bone fractures, infertility, and an increased risk for small bowel malignancy.

Celiac disease is diagnosed when sufficient damage to the intestinal tract is seen on biopsy. Anyone with evidence of IgG or IgA antigliadin antibodies is considered to have gluten sensitivity, even without evidence of other intestinal antibodies, such as endomysial antibodies, now known as tissue transglutaminase antibodies. (1) People with gluten sensitivity have immunological reactions when they ingest proteins called prolamines, including gliadin in wheat, secalin in rye, and hordein in barley. When sensitive people ingest these compounds, these proteins react with immunologically active cells present in the gastric mucosa. In turn, these immune-system cells respond by producing cellular changes and immune-system chemicals that lead to the destruction of the intestinal microvilli. This interferes with nutrient absorption and leads to the stimulation and over-proliferation of intestinal B-lymphocytes.

A long list of symptoms

Gluten sensitivity causes malabsorption, which is the inability to properly absorb nutrients from food. Because patients with gluten sensitivity often only have mild symptoms and do not show the intestinal changes associated with celiac disease, they are likely to be misdiagnosed and not advised to avoid gluten. Symptoms in gluten sensitivity are also wide-ranging, varied, and not easily recognizable as such. Typical among them are abdominal pain, abdominal distention, weight loss, irritability, depression, muscle wasting of buttocks, thighs and arms, pale skin, peeling nails, alopecia, bloating, lactose intolerance, delayed puberty, miscarriage, arthralgia, bone pain, fatigue, gas, nausea, vomiting, increased mucus production, nasal discharge, diarrhea, increased fat in stools (steatorrhea), iron-deficiency anemia, osteopenia, osteoporosis, apthous (oral) ulcerations, dental-enamel defect, miscarriage, joint pain, Sjogren's syndrome, Turner's syndrome, and elevated liver enzymes. Patients may also gain weight if nutrient deficiencies lead to food cravings and fatigue. (1)

Children with celiac disease may present with failure to thrive; their abdomens may be large and distended. Disorders that may accompany gluten sensitivity in children include short stature, selective IgA deficiency, dementia, Down syndrome, Williams' syndrome, Addison's disease, type 1 diabetes, infertility, autoimmune thyroid disease, primary biliary cirrhosis, and rheumatoid arthritis. Some researchers feel that the toxic components in gluten contribute to the development of these other autoimmune diseases. (1)

Difficult diagnosis

Diagnosing celiac disease is difficult. The usual approach is to order tests for gliadin and tissue transglutaminase (or endomysial) antibodies and serum IgA levels. Many physicians, however, fail to order tests for serum IgA levels. Because patients with gluten sensitivity often have low immunoglobulin levels, various antibody tests for IgA autoantibodies will be negative. For this reason, the presence of IgG gliadin antibodies alone in someone with a low IgA level (less than 10) should be referred to a gastroenterologist for further evaluation including intestinal biopsy, if indicated. On biopsy, intestinal changes are often seen in people with gluten sensitivity--even when symptoms are mild. The ultimate confirmation for gluten sensitivity, however, is the absence of symptoms after following a gluten-free diet.

Celiac disease is unique, in that the environmental factor that causes disease in persons with specific immune-system disease has clearly been identified and is required for disease expression. Traditionally, antibody tests for gliadin and endomysial or tissue transglutaminase antibodies, and intestinal biopsy have been used to diagnose celiac disease. In addition, tests for HLA genotypes DQ2 and DQ8 found on chromosome six are available for diagnosing celiac disease. More than 90% of patients with celiac disease have DQ2, and most remaining patients, about 8%, have the DQ8 allele. The molecules formed by these genetic markers present gluten to the immune system, which drives the autoimmune-disease process.

These markers are present, however, in individuals who do not develop celiac disease. Thus, the test is more suited for determining the genetic risk or probability of developing celiac disease, or for ruling out the possibility of developing celiac disease (negative results for these genetic markers). Individuals with other autoimmune diseases such as type 1 diabetes, Addison's disease, and autoimmune-thyroid disease are more likely to have these genetic markers, making people with these disorders more susceptible to celiac disease. Celiac disease is also more common in certain genetic diseases such as Down, Turner's, and William's syndromes.

Lifelong dietary change with full removal of dietary gluten is necessary for treating gluten sensitivity. Untreated gluten sensitivity can lead to secondary diseases resulting from disruption of the normal intestinal barrier. The presence of leaky gut (see sidebar on page 17), which allows for abnormal intestinal permeability, is a well-documented affect. This can lead to the ingestion of toxins and other antigens that can aggravate or cause disease in other organs. Scientists have studied the amount of gluten that can be safely ingested in patients sensitive to gluten and found that there is no safe amount. Amounts as low as 0.1 grams led to clinical relapses and changes in intestinal tissue. (1)

Celiac and thyroid disease

Celiac disease often occurs in patients with autoimmune-thyroid disease. Untreated celiac disease can also cause resistance to thyroid-replacement hormone. In a study, French researchers described the value of testing for celiac disease after a 68-year old female patient failed to respond to adequate amounts of thyroid-replacement hormone. (3)

This patient also showed poor absorption of the vitamin D analogue alfacalcidol, which is used to increase calcium absorption and prevent bone loss.

Because she did not show the typical digestive symptoms of diarrhea, bloating, and nausea that are characteristic of celiac disease, her condition eluded diagnosis. In this case, malabsorption was eventually suspected when the patient failed to respond to high doses of thyroid-replacement hormone. Although blood levels of thyroid hormone increased after loading doses of thyroid-replacement hormone, oral replacement hormone was ineffective until the patient was put on a gluten-free diet.

In patients with either hypothyroidism, or hyperthyroidism or Graves disease, the incidence of gluten sensitivity is increased. In hyperthyroidism, malabsorption impacts related symptoms (e.g., hair, skin, and nail changes; mood disorders; and weight loss). The fast transit of food molecules, particularly oil-soluble substances including thyroid replacement hormone and the hormone vitamin D, through the intestines causes incomplete nutrient absorption. Typically, stool fat content is increased in malabsorption. In patients with autoimmune untreated celiac disease can contribute to hyperthyroidism, whose symptoms are related to malabsorption and nutrient deficiencies. (4)

References

1. Braly J, Hogan R. Dangerous Grains, Why Gluten Cereal Grains May Be Hazardous to Your Health. New York: Avery, 2002.

2. Not T, MD. Dietary Gluten in Celiacs Linked to Organ-Specific Autoantibodies. Digestive Diseases and Science. February 2000;45:403-406.

3. Gluten-induced enteropathy (celiac disease) revealed by resistance to treatment with levothyroxine and alfacalcidol in a sixty-eight-year-old patient: a case report. Department of Endocrinology, Hospital Rangueil, Toulouse, France. Available at: www.thyroidmanager.org/chapter9/chapter9.pdf. Accessed March 23, 2007.

4. Medeiros L, NP. Celiac Disease, A condition with multiple faces, Advance for Administrators of the Laboratory, June 2006.

RELATED ARTICLE: Leaky gut syndrome

Many autoimmune disorders show signs of intestinal permeability or leaky gut syndrome, which is thought to contribute to disease development and worsen symptoms. Leaky gut syndrome describes an inability of the stomach lining to absorb protein molecules. Instead of being digested and broken down, these protein molecules circulate throughout the bloodstream. Here, they stimulate the immune system; and, in turn, immune-system cells react to their presence--as they would to any foreign protein--by initiating an inflammatory reaction that leads to autoantibody production and autoimmune-disease development.

Evidence for this theory includes the presence of gastrointestinal tissue damage seen in patients with a number of different autoimmune diseases including ankylosing spondylitis, irritable bowel syndrome, rheumatoid arthritis, Crohn's disease, multiple sclerosis, vasculitis, thryroiditis, and dermatitis herpetiformis. In many of these conditions, a reduction of digestive inflammation correlates with a reduction or remission of autoimmune symptoms.

Medical practitioners today think that leaky gut syndrome is caused by a substance or combination of substances, such as allergens or toxins, which initiate inflammation in the digestive tract. This inflammation allows for large molecules to pass across the intestinal barrier, including molecules from proteins, fats, parasites, bacteria, and fungi. Because human tissues have protein antigens similar in structure to these other proteins, the scene is set for autoimmune-disease development.

Causes and symptoms of "leaky gut"

Common causes of leaky gut syndrome include antibiotics, alcohol, caffeine, parasites, bacteria, some food preservatives and additives, and allergic states (e.g., gluten sensitivity and lactose intolerance, corticosteroids, non-steroidal anti-inflammatory drugs, refined carbohydrates, oral contraceptives, and fungi). Chronic inflammation from these sources damages the protective coat of immunoglobulin (antibody) A, which interferes with the body's normal ability to inhibit these substances. The resulting toxins then interfere with the liver's ability to detoxify them.

One result is increased sensitivity to environmental agents such as cigarette smoke, chemical cleaning agents, and strong perfumes. Early symptoms include a tendency toward hay fever. Other symptoms include nutrient deficiencies, acne, headaches, poor concentration, fatigue, and irritability, With aging and exposure to stress, a gradual loss of stomach acid occurs, which can aggravate the problem and contribute to vitamin B12 deficiency and deficiencies of minerals such as chromium, copper, iron, magnesium, manganese, selenium, and zinc.

Treatment

Oral supplementation with friendly bacteria and digestive enzymes help restore intestinal permeability. Substances known as probiotics supply these friendly bacteria. Probiotics include tablets containing Lactobacillus acidophilus, Propionibacterium freudenreichii shermanii, and Bifidobacterium bifidum. The recommended dosage is 6 to 18 billion bacteria used three times daily. Added polysaccharides in these preparations also offer benefits.

Eliminating or reducing substances that promote intestinal permeability also promotes intestinal healing. This includes avoiding antibiotics, non-steroidal anti-inflammatory drugs, pesticides, herbicides, and meat contaminated with hormones. Substances that promote healing include high-fiber foods rich in antioxidants, such as cabbage, cauliflower, beets, and onions; omega-3 fatty acids found in salmon and flaxseed, multi-mineral supplements, and digestive enzymes such as bromelain and pancreatin.

Resources

Kajander K, Hatakka K, Poussa T, Farkkila M, Korpela R. A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention. Aliment Pharmacol Ther. September 1, 2005;22(5):387-394.

Verdu EF, Collins SM. Irritable bowel syndrome and probiotics: from rationale to clinical use. Current Opinions in Gastroenterology. November 2005;21(6):697-701.

RELATED ARTICLE: Autoimmune atrophic gastritis leads the way to pernicious anemia

Atrophic gastritis is a condition of chronic inflammation and atrophy (tissue destruction) affecting the stomach's mucosal lining. Over time, atrophic gastritis leads to a loss of the gastric glandular and chief cells, a subsequent breakdown of the mucosal lining, and an eventual replacement of the mucosa by intestinal and fibrous tissue.

Atrophic gastritis has two causes:

1) an autoimmune process targeting parietal cells or intrinsic factor, and

2) environmental causes such as persistent infection with Helicobacter pylori bacteria or dietary factors.

Recent evidence suggests that H pylori can trigger the development of autoimmune atrophic gastritis through a process of molecular mimicry in which the bacterial organisms take on the antigenic appearance of parietal cells.

These two types of gastritis are distinct, with each disorder causing different tissue changes when biopsy samples are examined. In autoimmune gastritis, tissue destruction is restricted to the gastric corpus and fundus, whereas infectious gastritis is a multi-focal process with more extensive involvement of the strictures related to the gastric corpus and fundus. Atrophic gastritis associated with H pylori is also less likely to cause symptoms and more likely to lead to the development of stomach cancer.

In autoimmune atrophic gastritis, autoant-bodies cause destruction of the parietal cell mass that makes up the gastric mucosa. The autoimmune response causes an infiltration of white blood cells and the release of chemical cytokines that accelerate the disease process. Ultimately, the autoimmune response impairs the mucosal cells' ability to produce hydrochloric acid; digestive enzymes such as pepsin and intrinsic factor, a substance needed for the absorption of vitamin B12.

Signs and symptoms

Several mechanisms contribute to the signs and symptoms of pernicious anemia. Deficiencies of intrinsic factor lead to vitamin B12 deficiency and a condition of pernicious anemia. Deficiencies of hydrochloric acid (hypochlorhydria) induce the production of gastrin-producing or G cells. Increased proliferation of G cells causes excess gastrin production, which, in turn, increases the risk for development of gastric polyps and gastric adenocarcinoma (stomach cancer).

Early in the course of the disease, symptoms rarely occur, although mild symptoms of indigestion may be present. Autoimmune atrophic gastritis is the most frequent cause of pernicious anemia in temperate climates. The risk of gastric adenocarcinoma is reported to be at least 2.9 times higher in patients with pernicious anemia than in the general population. Patients with pernicious anemia are also at increased risk for esophageal squamous-cell carcinomas.

Autoimmune atrophic gastritis typically causes symptoms related to vitamin B12 (cobalmin) deficiency, including anemia, gastrointestinal symptoms, and neurologic symptoms, including dementia. Megaloblastic anemia may develop and, rarely, platelet deficiency (thrombocytopenia) may occur. Symptoms of anemia include weakness, light-headedness, vertigo, tinnitus, palpitations, angina, and symptoms of congestive heart failure as well as sore tongue, weight loss, irritability, mild jaundice, and heart enlargement.

Diagnosis and treatment

Patients with autoimmune atrophic gastritis have high levels of antiparietal and anti-intrinsic factor antibodies (types 1 and 2 antibodies to intrinsic factor). These antibodies result in low levels of intrinsic factor and deficiencies of vitamin B12. Treatment of atrophic gastritis focuses on reducing inflammation and avoiding environmental triggers such as spicy foods, and increasing levels of vitamin B12 and folic acid. Treatment for pernicious anemia eventually reduces the symptoms caused by nutrient deficiencies.

Incidence

The frequency of atrophic gastritis is not known because chronic gastritis does not usually cause symptoms. Females are at higher risk for autoimmune atrophic gastritis with three times as many women affected as men. Patients with other autoimmune disorders, especially autoimmune-thyroid disorders, are more likely to develop atrophic gastritis, the most common autoimmune disease to develop in patients with Graves disease who have been treated with radioiodine. Autoimmune atrophic gastritis is more frequent in individuals of northern European descent and in African-Americans; it is much less common in people of southern European descent and in Asians. Atrophic gastritis is not usually detected until the sixth decade of life when symptoms of pernicious anemia develop, although pernicious anemia has been detected in people of all ages. [See "Pernicious Anemia" by Dr. Vijay Kumar on pages 30-31 in the February 2007 issue of MLO.]

Resources

Sepulveda A. Gastritis, Atrophic, eMedicine, March 22, 2006. Available at: http://www.emedicine.com/med/topic 851.htm. Accessed March 23, 2007.

Suovaniemi O, Harkonen M, Sipponen P, Paloeimo L. GastroPanel, Diagnosing Atrophic Gastritis from Serum-Providing a Tool for Evidence-Based Medicine, Business Briefing: European Pharmacotherapy 2003.