Functional heterogeneity in the fermentation capabilities of the healthy human gut microbiota

Abstract

AbstractThe human gut microbiota is known for its highly heterogeneous composition across different individuals. However, relatively little is known about functional differences in its ability to ferment complex polysaccharides. Throughex vivomeasurements from healthy human donors, we show that individuals vary markedly in their microbial metabolic phenotypes (MMPs), mirroring differences in their microbiota composition, and resulting in the production of different quantities and proportions of Short Chain Fatty Acids (SCFAs) from the same inputs. We also show that aspects of these MMPs can be predicted from composition using 16S rRNA sequencing. From experiments performed using the same dietary fibersin vivo, we demonstrate that an ingested bolus of fiber is almost entirely consumed by the microbiota upon passage. We leverage ourex vivodata to construct a model of SCFA production and absorptionin vivo, and argue that inter-individual differences in quantities of absorbed SCFA are directly related to differences in production. Taken together, these data suggest that personalized dietary fiber supplementation based on an individual’s MMP is an attractive therapeutic strategy for treating diseases associated with SCFA production.