2025 Oct 13
Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT, United States
Colonization by Akkermansia muciniphila modulates central nervous system autoimmunity in an ecological context-dependent manner
https://pubmed.ncbi.nlm.nih.gov/41159034/
Results: We found that A. muciniphila colonization increased EAE severity only in a specific microbiome context, in conjunction with increased Th17 responses and CNS-infiltrating immune cells. Profiling of gut microbiome composition revealed that A. muciniphila colonization drove a reduction of Clostridia, key producers of SCFAs, specifically in the microbiome model in which A. muciniphila exacerbates EAE. Inferred metagenomic analyses suggested reduced SCFA production in the presence of A. muciniphila, which was confirmed by mass spectrometry. Consistently, provision of high dietary fiber as a substrate for SCFA production suppressed EAE only in the context of the Clostridia-rich microbiome sensitive to A. muciniphila colonization.
Discussion: Taken together, our data suggest that the effect of A. muciniphila on CNS autoimmunity is highly dependent on the overall composition of the gut microbiome and suggest that this microbe may contribute to decreased gut SCFA metabolism in multiple sclerosis. 
