Work

Impact of gut commensal competitive interaction on type 1 diabetes: Emphasis on Bacteroides fragilis and Akkermansia muciniphila 3739

Year: 2025

Type: article

Abstract: Description Type 1 diabetes (T1D) is an autoimmune disorder marked by T-cell-mediated destruction of insulin-producing beta cells, leading to chronic insulin deficiency. While genetic factors influence susceptibility, evidence increasingly highlights the role of environmental triggers, particularly gut microbiome dysbiosis in disease progression. Our ongoing investigations show that gut colonization of juvenile NOD mice by human commensal Bacteroides fragilis triggers a proinflammatory response, accelerating disease progression. Microbial profiling of B.fragilis monocolonized mice shows that B.fragilis inhibits the establishment of other gut commensals, such as Akkermansia muciniphila. Since both B. fragilis and A. muciniphila inhabit the mucus layers of the distal gut epithelium, we hypothesize that B. fragilis competitively excludes A.muciniphila from the colonic microbial niche,contributing to accelerated T1D progression. This hypothesis is being tested using germ-free and specific pathogen-free NOD mice. Our co-colonization experiments in juvenile NOD mice reveal that B. fragilis suppresses A.muciniphila-induced gut colonization and anti-inflammatory responses. While A.muciniphila protects against insulitis, B.fragilis worsens it, reversing the delayed hyperglycemia onset associated with A.muciniphila. Our research on B.fragilis and A.muciniphila competition investigates their role in T1D and facilitates the development of microbial manipulation strategies for preventing T1D. Funding Sources NIH/NIDDK ROIDK136094 Topic Categories Mucosal and Regional Immunology (MUC)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1504