3018-LB: Competitive Interactions Among Gut Commensals in Type 1 Diabetes: Emphasis on Bacteroides and Akkermansia muciniphila

Introduction and Objective: Type 1 diabetes (T1D) is an autoimmune disease characterized by T cell-mediated destruction of pancreatic β cells. Although genetic susceptibility contributes to disease risk, the gut microbiota has emerged as a critical environmental modifier of T1D pathogenesis. Alterations in early-life microbial colonization, intestinal barrier integrity, and mucosal immune responses are increasingly recognized as interconnected factors influencing disease initiation. While Akkermansia muciniphila has demonstrated protective effects in preclinical models, Bacteroides species, including Bacteroides fragilis and Bacteroides dorei, are associated with pathobiont activity in T1D. We investigated whether Bacteroides species competitively exclude protective commensals and promote disease progression. Methods: In vitro co-culture assays were used to evaluate interactions between Bacteroides spp. and A. muciniphila. Germ-free (GF) and specific pathogen-free (SPF) non-obese diabetic (NOD) mice were mono- and co-colonized with defined human gut commensals. Microbial colonization, mucin production, immune responses, and diabetes progression were assessed. Results: B. fragilis and B. dorei inhibited A. muciniphila growth in vitro. In NOD mice, colonization with Bacteroides spp. reduced mucin production, suppressed A. muciniphila colonization, enhanced pro-inflammatory immune responses, and accelerated T1D progression. In contrast, A. muciniphila preserved mucosal integrity and reduced insulitis. Conclusion: Ongoing studies employing mouse models, intestinal organoids, and epithelial cell culture systems aim to define the mechanisms and dynamics of competitive interactions among these human gut commensals and to determine their impact on microbial community structure and function, intestinal physiology, mucosal and systemic immunity, and T1D progression. These investigations are expected to inform microbiome-based strategies for the prevention of T1D. Disclosure R. Maurya: None. R. Jalandra: None. M. Mulligan: None. R. Gudi: None. C. Westwater: None. C. Vasu: None. Funding American Diabetes Association (1-26-PDF-0936), R01DK136094