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Updated: Sep 25, 2026

An Intestinal Gut Organ Culture System for Analyzing Host-Microbiota Interactions
Published on: June 30, 2021
Gut archaea drive human MAIT cell responses
Abstract:
Archaea, the third domain of life, are a gut microbiome constituent, but their role in shaping immunity is poorly understood. Mucosal-associated invariant T (MAIT) cells sense microbial metabolites through their T cell receptor and contribute to antimicrobial defence and barrier homeostasis. Key sources of the major MAIT cell antigen 5-OP-RU within the human gut microbiome are unknown. Analysing microbiomes from UK, Zambian, Kenyan and Ugandan donors, we found strong correlations between archaeal riboflavin biosynthesis and circulating MAIT cell frequency and activation. Stool 5-OP-RU levels correlated with archaeal abundance. Cultures of methanogenic archaea, including the human commensal Methanobrevibacter smithii , produced 5-OP-RU and strongly activated MAIT cells without inflammation. We demonstrate a critical role for archaea in shaping human immunity, with implications for microbiome-mediated regulation of health.
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