Identification of a key genetic factor governing arabinan utilization in the gut microbiome suggests a novel therapeutic target for constipation

Abstract

SUMMARYProbiotics have been widely used to improve impaired gastro-intestinal motility, yet their efficacy varied substantially across strains. Here, by a large-scale genetic screen plusin vivomeasurements, we identified a key genetic factor (abfAcluster governing arabinan utilization) in probioticBifidobacterium longumharnessing the treatment efficacy against functional constipation (FC). Intriguingly, it also presents in a range of gut resident microbiota and played a protective role against FC. Next, our longitudinal multi-omics study in humans revealed that the exogenousabfA-cluster- carryingB. longumcan well establish itself in the gut, and enrich arabinan-utilization residents and beneficial metabolites (e.g., acetate, butyrate, chenodeoxycholic acid and uracil). Finally, transplantation ofabfA-cluster-enriched human microbiota to FC- induced germ-free mice recapitulated the marked gut-motility improvement and elevated production of beneficial metabolites. Collectively, our proof-of-concept study actively demonstrated a critical yet underexplored role of microbialabfAcluster in ameliorating FC, establishing generalizable principles for developing functional-genomics-directed probiotic therapies.