February 2013 Issue

Gut Health and Autoimmune Disease — Research Suggests Digestive Abnormalities May Be the Underlying Cause
By Aglaée Jacob, MS, RD
Today’s Dietitian
Vol. 15 No. 2 P. 38

Tiffany, 31, transitioned her whole family to a 100% gluten-free diet when her 3-year-old daughter was diagnosed with celiac disease. To Tiffany’s surprise, her daughter wasn’t the only one to benefit from eliminating wheat and other gluten grains from her diet.

At Tiffany’s follow-up visit with her rheumatologist, the doctor was impressed by the marked reduction in her C-reactive protein and erythrocyte sedimentation rate levels, two inflammatory markers indicating disease activity in rheumatoid arthritis (RA), a common autoimmune condition. Tiffany now feels better than she has in years and is excited to wake up pain free every day since changing her way of eating.

Autoimmune conditions such as RA tend to run in families, and many of these conditions seem to start in the gut.

A Peril on the Rise
To date, at least 80 different autoimmune diseases have been identified, and an additional 40 illnesses are suspected to have an autoimmune component, according to the American Autoimmune Related Diseases Association (AARDA), a nonprofit health agency increasing the awareness of autoimmune diseases. Autoimmune conditions are chronic and can affect every organ in the body, crossing almost all medical specialties, including gastroenterology, cardiology, neurology, rheumatology, gynecology, dermatology, and endocrinology.

The prevalence of autoimmune disorders is rapidly rising and now affects an estimated 23.5 million Americans, 75% of them women.1 In fact, autoimmune diseases are now among the top 10 leading causes of death in American women under the age of 65.

Emerging research shows that most autoimmune conditions may share a common root hiding in the intestinal lining of individuals with autoimmune diseases, even years before the symptoms manifest.

Inside the Gut
The intestines are the largest mucosal interface between the environment and us. A single layer of epithelial cells is all that separates the bloodstream and the contents of the intestines. The small intestine has the complex and crucial role of allowing nutrients inside the body while keeping bacteria, toxins, and wastes outside. The tight junctions separating the intestinal cells assume some of these functions.

The tight junctions aren’t cemented as previously thought but rather are dynamic structures. Incompetent tight junctions cause increased intestinal permeability, commonly referred to as leaky gut, and can result in the absorption of incompletely digested protein and antigens that overstimulate the immune system through the bloodstream.

Autoimmune Triad
Alessio Fasano, MD, a world-renowned pediatric gastroenterologist, research scientist, and founder of the University of Maryland Center for Celiac Research, believes all autoimmune conditions have three factors in common: a genetic susceptibility, antigen exposure, and increased intestinal permeability.2

“Besides celiac disease, several other autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, are characterized by increased intestinal permeability secondary to non-competent tight junctions that allow the passage of antigens from the intestinal flora, challenging the immune system to produce an immune response that can target any organ or tissue in genetically predisposed individuals,” Fasano wrote in the February 2012 issue of Clinical Reviews in Allergy and Immunology.2

While it was previously believed that the autoimmune process remained ongoing once activated, this recent evidence indicates that the process could be modulated and possibly reversed by interrupting one of the modifiable factors involved in the autoimmune triad.

Gluten and Zonulin
According to this theory, improving intestinal permeability could better the management of autoimmune conditions. In susceptible individuals, the zonulin system is one of the main pathways that could be responsible for disregulating the tight junctions and perpetuating the autoimmune process by allowing further damage to the target organ and worsening symptoms. Zonulin is normally present in the intestines to control the passage of fluids, macromolecules, and leukocytes, but this protein appears to be overexpressed in patients with autoimmune conditions, resulting in increased intestinal permeability.

Gluten, or any one of its 50 toxic epitopes, is one factor that can modulate zonulin secretion. “Once gluten is removed from the diet, serum zonulin levels decrease, the intestine resumes its baseline barrier function, the autoantibody titers are normalized, the autoimmune process shuts off and, consequently, the intestinal damage heals completely,” Fasano wrote.

In other words, increased intestinal permeability could contribute to the autoimmune response in genetically predisposed individuals. Studies have shown that this process could be involved not only in celiac disease but also in a significant number of type 1 diabetes, multiple sclerosis, and ankylosing spondylitis cases. Abnormal intestinal permeability also has been been shown to be present up to one year before a clinical flare-up of inflammatory bowel disease (IBD).

SIBO as a Contributor
Small intestinal bacterial overgrowth (SIBO) recently has been recognized as an underlying cause of many cases of irritable bowel syndrome (IBS), clinical relapses of Crohn’s disease, and celiac patients unresponsive to a gluten-free diet.3-5 SIBO is a chronic infection of the small intestine, resulting in the excessive fermentation of dietary carbohydrates and the accompanying flatulence, bloating, abdominal pain, diarrhea, and constipation.

 “SIBO and autoimmunity are related in several ways,” notes Allison Siebecker, ND, MSOM, Lac, a naturopathic physician and SIBO expert. SIBO is common in many autoimmune diseases, such as IBD, scleroderma, celiac disease, and Hashimoto’s hypothyroidism, although the exact nature of these associations isn’t fully known, Siebecker says. Moreover, she says increased intestinal permeability, which has been demonstrated in SIBO, is one of the three underlying causes of autoimmunity, as demonstrated by Fasano and his team, along with an environmental trigger and genetic predisposition. “SIBO, with its high likelihood of generating leaky gut, will need to be corrected for both prevention and treatment of autoimmunity,” she says.

SIBO can be successfully treated with antibiotics. Rifaximin and neomycin usually are preferred because their poor absorbability into the bloodstream maximizes their efficacy within the digestive tract while minimizing systemic side effects. Elemental diet formulas providing all energy requirements for a period of two to three weeks also are alternative treatment options.

Diagnostic Testing
As dietitians, requesting additional testing for patients suffering from autoimmune conditions can help determine whether their intestinal health is associated with their symptoms.

Considering that many people have more than one autoimmune condition, testing for celiac disease is a good place to start. Positive results can help motivate clients to embrace a gluten-free diet to normalize their intestinal permeability. Dietitians should be aware that only about one-half of celiac patients demonstrate the condition’s “classic” symptoms at diagnosis, according to a study published in the February 2001 issue of Gastroenterology. It’s important to remember that celiac disease testing isn’t reliable if clients haven’t been consuming sufficient quantities of gluten in the previous weeks.

Testing for SIBO is appropriate for clients presenting with any type of gastrointestinal complaints mimicking IBS, considering SIBO’s strong connection with autoimmune diseases. A simple and noninvasive lactulose or glucose breath test can reveal whether SIBO could be altering patients’ intestinal permeability and therefore contributing to the autoimmune process.

The lactulose/mannitol test used to monitor intestinal permeability is reserved mostly for clinical research, but it’s available in some commercial labs and can be a useful tool to track the impact of dietary and lifestyle changes over time. If taken at home, the procedures for this test must be followed carefully to receive accurate results. A zonulin ELISA assay, predicted to be available in the near future, also could be a tool dietitians use to detect and monitor intestinal permeability in patients affected by autoimmune conditions.

Dietitian’s Role
Since intestinal permeability is the main factor of the autoimmune triad, which can be modulated, dietitians can play a role in helping treat and manage patients. The abnormal intestinal permeability associated with autoimmune conditions doesn’t necessarily result in digestive symptoms, but it doesn’t hurt to adopt dietary strategies to minimize gut irritants and maximize intestinal health-promoting nutrients to optimize the integrity of the gut lining and possibly slow down the autoimmune reaction.

Elimination Diet
South Dakota-based dietitian Amy Kubal, MS, RD, LN, with many clients who have autoimmune conditions whose overall health improved by first addressing digestion, uses an elimination diet approach to personalize her clients’ diets. “Certain foods like wheat, gluten, soy, dairy, eggs, nightshade vegetables, nuts, and processed products contain proteins and other components that may, in some individuals, contribute to ‘leaky gut’ and other autoimmune conditions,” Kubal says.

Even without a diagnosis of celiac disease, non-celiac gluten sensitivity should be suspected. With a prevalence six times higher than that of celiac disease, the existence of gluten sensitivity was finally confirmed in a breakthrough study published by the University of Maryland School of Medicine in the March 2011 issue of BMC Medicine. In addition, the high luminal antigliadin antibodies found in SIBO patients put them at increased risk of developing gluten intolerance or celiac disease, according to a study published in August 1997 in the American Journal of Gastroenterology.

Besides the zonulin-stimulating potential of gluten, the large proteins in nuts, eggs, soy, and many grains have a high allergenic potential, while nightshade vegetables (eg, white potatoes, bell peppers, eggplants, tomatoes) contain potentially problematic glycoalkaloids. These foods should all be eliminated for at least four to six weeks to establish a baseline before moving on to the reintroduction phase under a qualified dietitian’s supervision.

During the elimination phase, RDs play an important role in teaching clients how to read food labels; identify hidden gluten, soy, and dairy ingredients; and prepare balanced meals with limited food choices. During the elimination phase, Kubal says that “focusing on real, whole foods that haven’t undergone extensive processing or genetic modification is important for both maintaining and healing the gut” and that “lean or pastured animal proteins, vegetables, some fruit, and healthy fats help to promote intestinal and overall health.”

Typical meals during the elimination diet phase should include nutrient-dense and anti-inflammatory foods with a low allergenic potential, such as chicken salads with leafy greens, avocado and olive oil-based vinaigrette, hearty stews of lean beef with a side dish of cauliflower, or grilled salmon sprinkled with lemon juice and served with a side of vegetables stir-fried in coconut oil.

In the case of an SIBO diagnosis, avoiding high-FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) foods, sugars, and refined carbohydrates also may be a necessary additional step to control digestive symptoms during the elimination phase.

Reintroduction Phase
After the elimination diet phase, patients with autoimmune conditions should be experiencing fewer symptoms. It’s not unusual for these clients to report better mood, energy, and digestion. Although an elimination diet can be restrictive, dietitians should emphasize the importance of the slow and systematic reintroduction of food and food groups into their clients’ diets. The challenged foods ideally should be spaced three to seven days apart, using progressively larger servings, whether it be nuts, wheat, gluten, dairy, FODMAPs, eggs, or soy.

RDs should encourage clients to keep a detailed food diary and take notes of their daily symptoms to review at follow-up appointments and determine which foods can safely become part of their diet again. Any changes in their digestion or worsening of symptoms usually associated with autoimmune conditions indicate that the newly challenged food should be eliminated for a longer period of time. Dietitians should reassure clients by explaining that food tolerance may improve over time as the competency of the tight junctions and the integrity of the intestinal lining have recovered.

Dietary Supplements for Gut Healing
In addition to removing potentially offending foods through an elimination diet protocol, dietitians can recommend dietary supplements to promote gut healing and improve autoimmune disease management. “There are some dietary supplements that may further boost gut health: probiotics, fermented cod liver oil, glutamine, digestive enzymes, and medium chain triglycerides can be potent gut healing helpers,” Kubal says.

Vitamin D also appears to play a key role in calming the autoimmune reaction by soothing inflammation and contributing to the integrity of the gut lining, according to a study published in the January 2008 issue of the American Journal of Physiology — Gastrointestinal and Liver Physiology. Since vitamin D food sources are scarce, dietitians should promote the use of vitamin D3 supplements and adjust the recommended dosage according to their clients’ 25-hydroxyvitamin D3 blood levels.

Probiotics also play an important role in alleviating inflammation in the intestines in addition to potentially benefit intestinal permeability by modulating tight junctions. RDs can help clients select the best strains and dosage of probiotics based on their tolerance level.

Bottom Line
Autoimmune conditions often are treated with drugs associated with serious side effects and long-term consequences. Some of them increase the risk of infections, menstrual irregularities, weight gain, cataracts, osteoporosis, and type 2 diabetes.

The emerging evidence connecting increased intestinal permeability with autoimmune conditions can help dietitians provide safe and effective dietary counseling to improve both their clients’ digestion and overall health, possibly reducing the need for medications.

Dietitians should give motivated clients information about the connection between gut health and autoimmune diseases to implement a well-designed elimination and reintroduction diet considering the low-risk potential and promising cost benefit of this food-based approach.

— Aglaée Jacob, MS, RD, is a freelance writer who specializes in diabetes education and digestive health, and is currently studying naturopathic medicine in Toronto.


Autoimmune Conditions
• Addison’s disease
• Ankylosing spondylitis
• Cardiomyopathy
• Celiac disease
• Crohn’s disease
• Dermatitis herpetiformis
• Endometriosis
• Graves’ disease
• Hashimoto’s thyroiditis
• Lupus
• Lyme disease (chronic)
• Multiple sclerosis
• Narcolepsy
• Peripheral neuropathy
• Pernicious anemia
• Psoriasis
• Restless legs syndrome
• Rheumatoid arthritis
• Type 1 diabetes
• Ulcerative colitis
• Vitiligo

— Source: American Autoimmune-Related Disease Association


1. Autoimmune statistics. American Autoimmune-Related Disease Association website. http://www.aarda.org/autoimmune_statistics.php. Accessed November 10, 2012.

2. Fasano A. Leaky gut and autoimmune diseases. Clinic Rev Allerg Immunol. 2012;42(1):71-78.

3. Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlated with symptom improvement in irritable bowel syndrome: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003;98(2):412-419.

4. Klaus J, Spaniol U, Adler G, Mason RA, Reinshagen M, von Tirpitz CC. Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn’s Disease. BMC Gastroenterol. 2009;9:61.

5. Tursi A, Brandimarte G, Giorgetti G. High prevalence of small intestinal bacterial overgrowth in celiac patients with persistence of gastrointestinal symptoms after gluten withdrawal. Am J Gastroenterol. 2003;98(4):839-843.