Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism

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 ÅkessonWilliam Agace, Christian Sina, Charlotte R. Kleiveland, Karsten Kristiansen, Tor E. Lea

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article number1093
JournalNature Communications
Volume12
Issue number1
Number of pages19
ISSN2041-1723
DOIs
Publication statusPublished - 2021

Bibliographical note

Funding Information:
This work was supported by the Norwegian Research Council (project 267655). B.A.H.J. was supported by Lundbeck Foundation (grant number: R232-2016-2425) and Novo Nordisk Foundation (grant number: NNF17OC0026698). A.-L.G. and A.M. were supported by Canadian Institutes for Heart Research and Sentinel North from the Canada First Research Excellence Fund.

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