Gellman, R. H. | Search bioRxiv

bioRxiv2023

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 of 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. Prevotellas 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. Statement on work with indigenous communitiesIn order to acquire scientific knowledge that accurately represents all human populations, rather than only reflecting and benefiting those in industrialized nations, it is necessary to involve indigenous populations in research in a legal, ethical, and non-exploitative manner (Abdill et al., 2022; Green et al., 2020). Here, we isolated live bacterial strains from anonymized fecal samples collected from Hadza hunter-gatherers in 2013/2014 (Fragiadakis et al., 2019; Merrill et al., 2022; Smits et al., 2017). Samples were collected with permission from the Tanzanian government, National Institute of Medical Research (MR/53i 100/83, NIMR/HQ/R.8a/Vol.IX/1542), the Tanzania Commission for Science and Technology, and with aid from Tanzanian scientists. A material transfer agreement with the National Institute for Medical Research in Tanzania specifies that collected samples are solely to be used for academic purposes. For more information on the consent practices followed, and our ongoing work to communicate the results of these projects to the Hadza, please see (Merrill et al., 2022; Olm et al., 2022).

microbiology↗

bioRxiv2022

Fermented foods restructure gut microbiota and promote immune regulation via microbial metabolites

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.

microbiology↗