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

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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
  • Christian Sina
  • Charlotte R Kleiveland
  • Karsten Kristiansen
  • Tor E Lea
Organisations
External organisations
  • University of Copenhagen
  • Technical University of Denmark
  • Norwegian University of Life Sciences
  • Norwegian Institute of Marine Research
  • University Medical Center Schleswig-Holstein Campus Kiel
  • Laval University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

Keywords

  • Animals, Diet, Forkhead Transcription Factors/immunology, Homeostasis/immunology, Interleukin-17/immunology, Intestine, Large/immunology, Intestine, Small/immunology, Male, Methylococcus capsulatus/chemistry, Mice, Inbred C57BL, Microbiota/immunology, Nuclear Receptor Subfamily 1, Group F, Member 3/immunology, Obesity/immunology, Proteins/immunology, T-Lymphocytes, Regulatory/immunology
Original languageEnglish
Article number1093
JournalNature Communications
Volume12
Issue number1
Publication statusPublished - 2021 Feb 17
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

These authors jointly supervised this work: Benjamin A. H. Jensen, Karsten Kristiansen, Tor E. Lea.