Gut archaea drive human MAIT cell responses
- 1University of Oxford
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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BibTeX
@misc{fisherpearson2026archaea,
title = {{Gut archaea drive human MAIT cell responses}},
author = {N. Fisher-Pearson and M. J. Lett and I. W. D. Maylam and C. S. J. Philip and M. Salio and R. J. Suckling and R. Simmons and K. Barnbrook and B. Swift and W. Jaoko and F. Kibengo and W. Kilembe and E. J. Sanders and M. C. Coles and C. F. Pearson and P. Cicconi and T. Hanke and N. M. Provine and P. Klenerman and J. S. Johnson},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.750638},
url = {https://www.biorxiv.org/content/10.64898/2026.09.11.750638v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Gut archaea drive human MAIT cell responses
AU - N. Fisher-Pearson
AU - M. J. Lett
AU - I. W. D. Maylam
AU - C. S. J. Philip
AU - M. Salio
AU - R. J. Suckling
AU - R. Simmons
AU - K. Barnbrook
AU - B. Swift
AU - W. Jaoko
AU - F. Kibengo
AU - W. Kilembe
AU - E. J. Sanders
AU - M. C. Coles
AU - C. F. Pearson
AU - P. Cicconi
AU - T. Hanke
AU - N. M. Provine
AU - P. Klenerman
AU - J. S. Johnson
PY - 2026
DA - 2026/09/11
PB - bioRxiv
DO - 10.64898/2026.09.11.750638
UR - https://www.biorxiv.org/content/10.64898/2026.09.11.750638v1
AB - 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.
ER -