Hadza Prevotella require diet-derived microbiota-accessible carbohydrates to persist in mice

Industrialization has transformed the gut microbiota, reducing the prevalence of Prevotella relative to Bacteroides . Here, we isolate Bacteroides and Prevotella strains from the microbiota of Hadza hunter-gatherers in Tanzania, a population with high levels of Prevotella . We demonstrate that plant-derived microbiota-accessible carbohydrates (MACs) are required for persistence of Prevotella copri but not Bacteroides thetaiotaomicron in vivo . Differences in carbohydrate metabolism gene content, expression, and in vitro growth reveal that Hadza Prevotella strains specialize in degrading plant carbohydrates, while Hadza Bacteroides isolates use both plant and host-derived carbohydrates, a difference mirrored in Bacteroides from non-Hadza populations. When competing directly, P. copri requires plant-derived MACs to maintain colonization in the presence of B. thetaiotaomicron , as a no-MAC diet eliminates P. copri colonization. Prevotella 's reliance on plant-derived MACs and Bacteroides ' ability to use host mucus carbohydrates could explain the reduced prevalence of Prevotella in populations consuming a low-MAC, industrialized diet.