Research & Education

The Connection Between Autoimmune Diseases and Intestinal Permeability

Autoimmune diseases are multifactorial, influenced by genetic predisposition, environmental factors, and, notably, the health of the gastrointestinal (GI) tract and gut microbiome. The intricate connection between immune and GI health has been extensively studied in recent decades. Unsurprisingly, a dysregulated immune system, as seen in autoimmune diseases, may be associated with an unhealthy GI tract, particularly intestinal permeability

The intestinal epithelium of the GI tract is a barrier for the host from the outside world. When the intestinal epithelial lining is compromised, toxins, antigens, and bacteria in the lumen can enter the bloodstream. This is commonly referred to as “leaky gut syndrome.” In certain individuals, this exposure to environmental factors may trigger the initiation and development of autoimmune diseases. Bacterial antigens can stimulate intestinal immune cells, thereby generating autoreactive cells that can migrate systemically to target peripheral organs and initiate an attack. Another route includes bacterial antigens themselves migrating systemically and generating autoreactive immune cells within the lymphatic system to the peripheral organs. 

Lactulose/mannitol or lactulose/rhamnose testing, a method used to assess intestinal permeability, has shown that the lactulose/mannitol or lactulose/rhamnose ratio increases in patients with multiple sclerosis, rheumatoid arthritis, type 1 diabetes, or celiac disease. Elevated lipopolysaccharide concentration and reduced tight-junction protein concentrations have been noted in patients with ankylosing spondylitis or autoimmune hepatitis, and elevated serum soluble CD14 concentrations have been observed in those with systemic lupus erythematosus – all indicators of intestinal permeability

There are several markers of gut barrier integrity that can be assessed through qPCR (quantitative polymerase chain reaction) testing, a functional fecal testing. This testing can specifically look at markers of zonulin, anti-gliadin, and secretory immunoglobin A (SIgA). Secretory IgA, the main immunoglobin in the intestinal mucosa, is crucial for promoting normal defense responses to antigens and pathogens in the GI and respiratory tracts. It also helps maintain a healthy gut microbial balance and protects against exposure to food-derived antigens. Anti-gliadin SIgA, which assesses the presence of fecal anti-gliadin antibodies, can indicate immune responses in the gut to gluten in the diet. Lastly, zonulin, a protein essential for the proper function of intercellular tight junctions in the GI tract, is considered a biomarker for barrier permeability. 

The gut microbial environment is another critical player in regulating normal gut immune function. Some researchers even propose that gut dysbiosis, an imbalance in the gut microbiome, can act as both a cause and an effect of autoimmunity. Numerous clinical trials have observed that patients with autoimmune diseases exhibit unbalanced and unhealthy gut microbial compositions compared to healthy volunteers. Moreover, the health of the gut microbiome may influence the epithelial barrier by controlling cytokine-induced barrier changes

Certain dietary or supplemental interventions may help support those seeking to promote a healthy GI microbiota, and therefore, may help promote normal intestinal barrier function. Some interventions include, but are not limited to:  

The connection between autoimmune diseases and intestinal permeability is gaining increasing interest. Understanding this connection may help encourage those with autoimmune diseases to support their overall intestinal barrier function to promote normal immune system balance. 

By Danielle Moyer Male, MS, CNS, LDN