Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+ROR\u03b3t+IL-17+ Tregs and improve metabolism

Benjamin Anderschou Holbech Jensen ,Jonas T Treebak ,Knut Rudi ,Si Brask Sonne ,William W Agace ,Stefanie Derer ,Lise Madsen ,Caroline Piercey Åkesson ,Aymeric Rivollier ,Christian Sina ,Stine Indrelid ,Nicole Von Burg ,Mads V Damgaard ,Jacob Bak Holm ,Yke Jildouw Arnoldussen ,Anne Laure Agrinier ,Inga Leena Angell ,Ida Søgaard Larsen ,Karolina Sulek ,Karsten Kristiansen ,Simone Isling Pærregaard ,Even Fjære ,C Kleiveland ,André Marette ,Tor Lea

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.

Highlights

Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health
We found a consistent increase in the levels of the three major as well as three minor classes of short-chained fatty acids (SCFAs) in the cecum of WDMcB fed mice compared to WDCNTL fed counterparts pointing towards not just taxonomically, and functionally, discrete microbiota profiles in the two groups of mice, supporting a beneficial health impact of dietary inclusion of McB lysates (Fig. 1F, G)
In this report, we explored the relationship between dietary nutrients and host-microbe interactions with a focus on immunometabolic response rates in the context of high fat, high sucrose, western diet (WD) feeding

Summary

Introduction

Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. 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. These data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis. Apart from alleviating global energy demands, if used as a nutrient source, such components may potently affect host physiology as recently reported for A. muciniphila[10] and Bifidobacterium bifidum[11] In the latter example, cell surface polysaccharides of B. bifidum were used to induce peripheral immune-tolerance via generation of regulatory T cells (Tregs). It remains unknown whether these cells exhibit normal, reduced or increased IL-17 levels, and how this translates to host physiology

Methods

Results

Conclusion