Impact of Diet on Intestinal Microbiota-Host Dynamics

The human gastrointestinal tract houses a complex gut microbiota, or microbiome that is tightly linked with numerous inflammatory and metabolic diseases. The gut microbiota influences local and systemic immune responses, chronic low-grade inflammation, and plays an important role in the pathogenesis of obesity-related insulin resistance, type 2 diabetes, and inflammatory bowel diseases. Diet is a key modulator of gut microbiota metabolism, composition, and functional capacity as well as human health. Despite recent progress, still relatively little is known about the mechanisms that connect specific diets and molecules within diet to the microbiota and human health. Fermented foods have been recently shown to increase human gut microbiota diversity and decrease markers of inflammation, and preliminary data within this application show that fermented vegetable brine (FVB), filter sterilized FVB (sFVB) and lactate (a major metabolite within sFVB) can induce regulatory T cells (Tregs) in mice. This application is focused on investigating molecules within fermented vegetable brine, with a focus on lactate, that are capable of modulating aspects of host biology relevant allergy and inflammation and understanding how cues from gut microbes impact these interactions. The goals of this application include (i) defining the mechanisms by which fermented foods vegetable brine facilitate the engraftment of new strains to increase microbiota diversity, (ii) characterizing the requirement of gut microbes in lactate induced Treg expansion, (iii) determining the host perception pathways that are responsible for lactate-induced Treg expansion in a mouse model. Aim 1 will determine how microbiota diversity acquisition, a feature of gut microbiomes linked to health, is promoted by fermented foods. This aim will reveal to what extent diversity increase is intrinsic to a microbiota versus requires exogenous microbes. Aim 2 will investigate the dependence of lactate induced Treg expansion on components of the gut microbiota. Experiments will identify how specific gut resident microbes impact Treg expansion in the presence of oral lactate and what molecular cues are required for Treg expansion. Aim 3 will employ mice genetically lacking lactate-binding G-protein coupled receptors to establish the basis of lactate perception. This project will advance our understanding of how fermented foods and metabolites within these foods impact the microbiota and host biology for improved health.