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Akkermansia muciniphila mediates negative effects of IFNg on glucose metabolism

ABSTRACT: we addressed whether the established dialogue between IFNg and glucose metabolism involves a third player – the gut microbiota. By using systems biology approaches and analyzing trans-kingdom interactions we found that, indeed, the effect of IFNg on glucose tolerance is mediated by one of the members of mouse gut microbiota, Akkermansia muciniphila. Further, we have identified Irgm1 as a IFNg-regulated host gene responsible for control of A. muciniphila levels in the gut. In addition, the investigation of human subjects revealed that A. muciniphila may play similar roles in mouse and human physiology.

PROVIDER: PRJEB15330 | ENA |

REPOSITORIES: ENA

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Project description:The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1-/Δ7 mice with A. muciniphila for 10 weeks and investigated histological, transcriptional and immunological aspects of intestinal health. The thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80+CD273- B cells in Peyer’s patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6Cint monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila. Altogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging.

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Akkermansia muciniphila mediates negative effects of IFNg on glucose metabolism

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