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

Nat Commun. 2021 Feb 17;12(1):1093. doi: 10.1038/s41467-021-21408-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Homeostasis / immunology
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Intestine, Large / immunology*
  • Intestine, Large / metabolism
  • Intestine, Large / microbiology
  • Intestine, Small / immunology*
  • Intestine, Small / metabolism
  • Intestine, Small / microbiology
  • Male
  • Methylococcus capsulatus / chemistry
  • Methylococcus capsulatus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Microbiota / immunology*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Obesity / immunology
  • Proteins / immunology*
  • Proteins / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Proteins

Associated data

  • figshare/10.6084/m9.figshare.13522283

Grants and funding