The human methanogens Methanobrevibacter smithii and Methanosphaera stadtmanae reinforce the colonic epithelial barrier, expand Foxp3+ Tregs without inducing TH17 responses, and protect mice from DSS-induced colitis, with MSt protection requiring adaptive immunity while MSm retains partial efficacy in lymphocyte-deficient mice.
MSm and MSt induce distinct colonic transcriptional programs in germ-free mice that are relevant to epithelial integrity.
MSm and MSt reinforce the colonic epithelial barrier in gnotobiotic and antibiotic-treated SPF mouse models.
Methanogens expand Foxp3+ regulatory T cell populations without inducing pro-inflammatory TH17 responses.
Both MSm and MSt protect against dextran sodium sulfate (DSS)-induced colitis in mice.
MSt-mediated protection from colitis requires adaptive immunity, whereas MSm retains partial efficacy in lymphocyte-deficient mice.
Archaea, which constitute up to 10% of the anaerobic gut community, have largely undefined functional roles in mucosal homeostasis, and the findings suggest methanogens promote mucosal integrity.
This study looked at two archaea, single-celled microbes distinct from bacteria, that live in the human gut: Methanobrevibacter smithii and Methanosphaera stadtmanae. Although archaea can make up to about 10% of the gut's oxygen-free microbial community, little is known about what they do. Using mice that were germ-free, colonized with defined microbes, or treated with antibiotics, the researchers found that these microbes triggered different gene activity in the colon and strengthened the gut lining. The mice had more mucus-producing goblet cells, a thicker mucus layer, and better renewal of the gut lining. The microbes also increased regulatory T cells, immune cells that help keep inflammation in check, without boosting TH17 cells, which promote inflammation. In mice given dextran sodium sulfate, a chemical that causes colitis, both archaea protected against disease. The protection worked differently for each species: M. stadtmanae needed a functioning adaptive immune system, while M. smithii still gave partial protection in mice lacking lymphocytes. This research suggests that gut archaea may contribute to a healthy gut lining and could one day inform approaches to inflammatory bowel disease. However, the work was done in mice, and the authors state that translation to human disease remains to be established.
Byrd E, Harris B, Zhang H, Warren W, Kolli S, Putelo A, et al.. (2026). Methanogenic archaea Methanobrevibacter smithii and Methanosphaera stadtmanae promote mucosal homeostasis and protect from colitis.. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2610622123