Fecal bacteria implicated in biofilm production are enriched and associate to gastrointestinal symptoms in patients with APECED – a pilot study

APECED is a rare autoimmune disease caused by mutations in the Autoimmune Regulator gene. A significant proportion of patients have gastrointestinal symptoms, including malabsorption, chronic diarrhea, and obstipation that lead to decrease in the quality of life. The pathological background of the gastrointestinal symptoms remains incompletely understood. We have previously found that patients with APECED have increased immune responses against gut commensals, but previous smaller studies have found only small alterations in the microbiota of the gut of the patients. Our objective was to evaluate whether the intestinal microbiota composition differs between patients with APECED (N=15) and healthy controls, and whether these are associated with the patients' clinical phenotype and gastrointestinal symptoms. We found both alpha- and beta-diversity to be altered in patients with APECED compared to healthy controls. Several gram-negative genera previously implicated in biofilm formation were increased in patients, in parallel with lipopolysaccharide (LPS) synthesis in imputed metagenomics. Interestingly, the most pronounced changes in the microbiota were associated with more severe gastrointestinal symptoms in patients with APECED, suggesting that gut microbiota is a factor to consider when contemplating therapy.