Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3(+)ROR gamma t(+)IL-17(+) Tregs and improve metabolism

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 degrees C) and at thermoneutrality (T30 degrees 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(+)ROR gamma t(+)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. Dietary changes can impact the microbial constitution of the gastrointestinal tract and modulate the local immune response. Here, the authors show supplementation using lysates of Methylococcus capsulatus Bath result in changes to the microbiota, modulate Treg populations and metabolic read outs in a dietary control murine model.