Industrialization has transformed the gut microbiota, reducing the prevalence ofPrevotellarelative toBacteroides. Here, we isolateBacteroidesandPrevotellastrains from the microbiota of Hadza hunter-gatherers of Tanzania, a population with high levels ofPrevotella. We demonstrate that plant-derived microbiota-accessible carbohydrates (MACs) are required for persistence ofPrevotella copribut notBacteroides thetaiotaomicron in vivo. Differences in carbohydrate metabolism gene content, expression, and in vitro growth reveal that HadzaPrevotellastrains specialize in degrading plant carbohydrates, while HadzaBacteroidesisolates use both plant and host-derived carbohydrates, a difference mirrored inBacteroidesfrom non-Hadza populations. When competing directly,P. coprirequires plant-derived MACs to maintain colonization in the presence ofB. thetaiotaomicron, as a no MAC diet eliminatesP. copricolonization.Prevotella'sreliance on plant-derived MACs andBacteroides'ability to use host mucus carbohydrates could explain the reduced prevalence ofPrevotellain populations consuming a low-MAC, industrialized diet.

Fermented foods are ancient and ubiquitous, thought to be consumed in nearly every culture over the last 10,000 years and as part of the hominin diet for millions of years. A growing body of evidence supports their potential health benefits, but the mechanistic basis of their effects on the gut microbiome and host immunity remain to be elucidated. Fermented foods are diverse, each representing a complex mixture of food, microbes, and metabolites creating a significant challenge to disentangle the effects of individual components. Herein, we further define the chemical signature of individual fermented foods to categorize them based on the primary metabolic end-products of fermentation. Using mouse models, we find that fermented foods have both microbiome directed as well as differential host directed effects that correspond to their metabolite composition. Fermented food brine drink shows site-specific restructuring of the gut microbiome and promotion of tolerogenic barrier immunity; fractionation of the brine to examine the effects of the microbe-free, metabolite rich supernatant shows similar activity. Lactate, the main metabolite of lactic acid fermentation and the major metabolite within the brine drink, when administered in water, fuels a trans-kingdom metabolic network to selectively promote the growth of Akkermansia muciniphila. in the small intestine, while promoting immune tolerance via an increase in microbiota-dependent Regulatory T-cells. These findings suggest that the beneficial effects of fermented food consumption can be mediated by microbial metabolites within fermented foods, independent of microbial content, and highlight the importance of further defining the diverse chemical landscape of fermented foods to inform their potential health benefits and therapeutic use.