Written by Dr. Megan Woroch, ND
Naturopathic Doctor in Toronto, Ontario
Published: September 13, 2026 · Updated: October 21, 2026
Autoimmune disease develops when the immune system loses tolerance to the body’s own tissues. Depending on the condition, this may affect the thyroid, joints, skin, nervous system, or other organs.
Genetics influence susceptibility, but they do not explain the whole picture. Environmental exposures, infections, digestive function and changes in immune regulation can contribute.
The connection between autoimmune disease and gut health involves the intestinal barrier, gut microbiome, and immune system. From a functional medicine perspective, understanding these interactions can help identify factors that may contribute to ongoing symptoms and immune activation.
The Autoimmune Triad: Genetics, a Trigger, and Barrier Dysfunction
One proposed model, described in intestinal barrier research by Dr. Alessio Fasano, brings together three interacting factors (1):
Genetic predisposition: inherited characteristics that influence immune responses.
An environmental trigger: an exposure that can initiate or amplify an immune response.
Increased intestinal permeability: altered barrier function that allows greater passage of substances across the intestinal lining.
This framework helps explain how an environmental exposure might interact with genetic susceptibility through the gut. It is a proposed model with particular relevance to conditions such as celiac disease, rather than a proven requirement for every autoimmune condition.
In practice, it encourages us to look beyond the diagnosis alone. What exposures, digestive changes, or inflammatory processes might be influencing immune activity’s immune activity?
Intestinal Permeability and Autoimmune Disease
The intestinal barrier includes a protective mucus layer and intestinal cells connected by structures called tight junctions (2). These structures help regulate the movement of substances across the gut lining.
When barrier function is disrupted, microbial components and other antigens may more easily reach immune cells beneath the lining (3). An antigen is a substance the immune system recognizes and responds to.
In susceptible individuals, this increased exposure may trigger inflammatory signalling, alter immune responses, and promote translocation of lipopolysaccharide (LPS), an endotoxin that can contribute to systemic inflammation (4).
Experimental research provides examples of this interaction. In one study, Enterococcus gallinarum moved beyond the intestine and promoted autoimmune responses in genetically susceptible mice (5). Researchers also identified bacterial DNA in liver samples from selected patients with autoimmune disease (6). These findings support a possible mechanism, but they do not yet establish a stool-test-based treatment for human autoimmunity.
The relationship can also work in both directions: barrier dysfunction may contribute to inflammation, while inflammation can further impair the barrier (7).
Dysbiosis: The role of the Microbiome
Dysbiosis describes an alteration in the microbiome's composition or function. This may involve expansion of certain organisms, reduced representation of others, or changes in the compounds microbes produce, such as short-chain fatty acids (SCFAs), compared with a “healthy microbiome.”
Some organisms are described as commensal. They may live in the gut without causing problems but can contribute to disease under certain conditions, depending on the host’s genetics and immune system.
The effects can depend on the bacterial strain, the surrounding microbial community, barrier function, and the person’s immune susceptibility.
Human research has identified several relevant associations:
Prevotella: overgrowth has been found in some people at risk of rheumatoid arthritis, including before established disease develops (8).
Ruminococcus gnavus: growth has been associated with lupus disease activity, particularly lupus nephritis (9).
Microbial metabolic function: the TEDDY study identified differences in microbial genes involved in fermentation and SCFA production in children who developed islet autoimmunity or type 1 diabetes compared with controls (10).
These findings help explain why the microbiome matters in autoimmune management. They do not mean that detecting one organism predicts whether someone will develop an autoimmune disease.
Stool Testing for Gut Health
In functional medicine, comprehensive stool testing may be considered when digestive symptoms or the broader clinical history suggest that further investigation could inform care.
Tests such as Diagnostic Solutions GI-MAP and US BioTek’s GI–Advanced Profile assess selected microbes alongside markers related to digestive function and intestinal health.
The clinical value comes from asking whether a finding fits the person’s symptoms, history, and other investigations, and whether it would meaningfully change the plan.
Zonulin and Intestinal Permeability
Zonulin is a signalling protein that helps regulate the tight junctions between intestinal cells (11). By reorganizing the proteins that maintain these connections, it can temporarily increase the passage of substances across the gut lining.
Gliadin, a component of gluten, can stimulate zonulin release. In studies using human intestinal biopsies, this response was limited and temporary in non-celiac tissue, but more pronounced and sustained in celiac tissue (12). This helps explain one way gluten can influence barrier function, although it does not mean gluten causes persistent intestinal damage or permeability.
From a functional medicine perspective, stool zonulin may provide an indirect clue about intestinal barrier function. I consider it alongside symptoms, microbial findings, secretory IgA, and inflammatory markers. These assess different aspects of gut health and help build a broader clinical picture.
Secretory IgA: Understanding Mucosal Immune Defence
Secretory IgA, or sIgA, is an antibody found in intestinal secretions and represents our mucosal immunity. It binds microbes and other antigens, limits their contact with the intestinal lining, and helps maintain a balanced relationship between the immune system and the microbiome (13).
Both low and high stool results may be relevant, but neither has a single explanation.
Low sIgA may suggest reduced mucosal antibody availability and may reflect reduced intestinal immunity and increased susceptibility to dysbiosis and intestinal infection (14).
High sIgA may reflect increased mucosal immune stimulation, often in response to an acute infection or dysbiosis (14).
The question is how the result fits with digestive symptoms, infection history, medications, other stool markers, and relevant blood work.
Looking at the Pattern
A functional medicine assessment brings these findings together.
For example, persistent digestive symptoms alongside altered microbial findings and an abnormal sIgA result may justify closer investigation of the intestinal environment. An elevated zonulin result may raise a question about barrier function.
These patterns can help generate a clinical hypothesis.
How This Can Guide Care
A gut-focused plan begins with identifying the person’s specific needs. Depending on the findings, this may include:
Investigating persistent digestive symptoms or a suspected gastrointestinal condition.
Addressing nutritional deficiencies, inadequate intake, or unnecessary food restrictions.
Gradually increasing tolerated fibre and plant variety.
Considering targeted dietary, probiotic, or other supportive interventions with a clear purpose.
Treating a confirmed infection when indicated.
Reviewing sleep, stress, medications, and other factors that may affect digestion and immune function.
Progress is monitored to include how the person feels and functions, nutritional status, and appropriate measures of disease activity.
A Functional Medicine Perspective on the Evidence
The gut–immune connection provides a meaningful framework for investigating autoimmune disease. Genetic susceptibility, environmental triggers, microbial activity, and barrier function may interact differently from one person to another.
Research supports many of these biological connections, while the ability to predict disease or select treatment from a commercial stool panel remains less established.
I use this information selectively, alongside a person’s history, lab work, and ongoing autoimmune care. The aim is to identify modifiable contributors to symptoms and immune activation, then build a practical plan.
Dr. Megan Woroch, ND, is a Toronto-based naturopathic doctor with a focus on digestive health, immune and environmental health, and root-cause approaches to chronic health concerns. She uses evidence-informed naturopathic medicine, clinical nutrition, functional testing, and individualized supplementation to support her patients.
Learn more about a naturopathic approach to digestive health and autoimmune disease.
Disclaimer: This information is for educational purposes only and is not intended to provide or replace medical advice, diagnosis, or treatment. Always consult your qualified healthcare provider for individualized recommendations.