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 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 () and Tor E. Lea ()
Additional contact information
Benjamin A. H. Jensen: University of Copenhagen
Jacob B. Holm: University of Copenhagen
Ida S. Larsen: University of Copenhagen
Nicole Burg: Technical University of Denmark
Stefanie Derer: University Hospital Schleswig-Holstein
Si B. Sonne: University of Copenhagen
Simone I. Pærregaard: University of Copenhagen
Mads V. Damgaard: University of Copenhagen
Stine A. Indrelid: Norwegian University of Life Sciences
Aymeric Rivollier: Technical University of Denmark
Anne-Laure Agrinier: Cardiology Axis of the Québec Heart and Lung Institute, Laval University
Karolina Sulek: University of Copenhagen
Yke J. Arnoldussen: Norwegian University of Life Sciences
Even Fjære: Institute of Marine Research
André Marette: Cardiology Axis of the Québec Heart and Lung Institute, Laval University
Inga L. Angell: Norwegian University of Life Sciences
Knut Rudi: Norwegian University of Life Sciences
Jonas T. Treebak: University of Copenhagen
Lise Madsen: University of Copenhagen
Caroline Piercey Åkesson: Norwegian University of Life Sciences
William Agace: Technical University of Denmark
Christian Sina: University Hospital Schleswig-Holstein
Charlotte R. Kleiveland: Norwegian University of Life Sciences
Karsten Kristiansen: University of Copenhagen
Tor E. Lea: Norwegian University of Life Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21408-9

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