Quantifying the daily harvest of fermentation products from the human gut microbiota

Markus Arnoldini, Richa Sharma^*, Claudia Moresi^*, Griffin Chure, Julien Chabbey, Emma Slack, and Jonas Cremer

Abstract

Fermentation products released by the gut microbiota provide energy and important regulatory functions for the host. Yet, little quantitative information is available on the metabolite exchange between the microbiota and the human host, and thus the effective doses of fermentation products. Here, we introduce an integrative framework combining experimental characterization of major gut bacteria with a quantitative analysis of human digestive physiology to put numbers on this exchange and its dependence on diet and microbiota composition. From the carbohydrates fueling microbiota growth, we find most carbon ends up in fermentation products which are largely utilized by the host. This harvest varies strongly with diet, from between 100-700 mmol/day within the US population to up to 1300 for the Hadza people of Tanzania. Accordingly, fermentation products cover between 1.8% and 12.1% of the daily energy demand of human hosts, substantially less than the 21% estimated for laboratory mice. In contrast, microbiota composition has little impact on the total daily harvest but determines the harvest of specific fermentation products, with butyrate showing the largest variation. Our framework thus identifies and quantifies major factors driving the metabolic and signaling interactions between microbiota and host, crucial to mechanistically dissect the role of the microbiota in health and disease.