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Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.

Citation

Benjamin A H Jensen, Jacob B Holm, Ida S Larsen, Nicole von Burg, Stefanie Derer, Si B Sonne, Simone I Pærregaard, Mads V Damgaard, Stine A Indrelid, Aymeric Rivollier, Anne-Laure Agrinier, Karolina Sulek, Yke J Arnoldussen, Even Fjære, André Marette, Inga L Angell, Knut Rudi, Jonas T Treebak, Lise Madsen, Caroline Piercey Åkesson, William Agace, Christian Sina, Charlotte R Kleiveland, Karsten Kristiansen, Tor E Lea. Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism. Nature communications. 2021 Feb 17;12(1):1093

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PMID: 33597537

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