Methanogenic Archaea Methanobrevibacter smithii and Methanosphaera stadtmanae Bolster Colonic Homeostasis and Ameliorate Colitis 47 views

The intestinal microbiota is a critical determinant of mucosal homeostasis, yet the functional contributions of Archaea—which constitute up to 10% of the anaerobic community—remain largely undefined. Here, we demonstrate that the prevalent human methanogens Methanobrevibacter smithii (MSm) and Methanosphaera stadtmanae (MSt) actively promote colonic health. Transcriptomic analysis of germ-free (GF) mice reveals that MSm and MSt induce distinct colonic programs essential for epithelial integrity. Using gnotobiotic and antibiotic-depleted conventional mouse models, we show that MSm and MSt colonization reinforce the epithelial barrier, characterized by increased goblet cell expansion, mucus thickening, and enhanced epithelial regeneration. Furthermore, methanogens expand Foxp3⁺ regulatory T cell (Treg) populations without inducing pro-inflammatory TH17 responses. Notably, MSm and MSt protect against dextran sodium sulfate (DSS)-induced colitis. While MSt- mediated protection requires adaptive immunity, MSm retains partial efficacy in lymphocyte-deficient mice, revealing nonredundant protective mechanisms. These findings establish methanogenic archaea as beneficial symbionts that bolster mucosal integrity and suggest their potential as therapeutics for inflammatory bowel disease (IBD).

PHD (Doctor of Philosophy)

Archaea; Methanogens; Microbiota; IBD

English

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2026-08-11