A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation.

Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics, such as Bifidobacteria , can improve this bowel disorder; however, efficacy is strain-dependent. We determine that a genetic factor, the abfA cluster governing arabinan utilization, in Bifidobacterium longum impacts treatment efficacy against functional constipation (FC). In mice with FC, B. longum , but not an abfA mutant, improved gastrointestinal transit time, an affect that was dependent upon dietary arabinan. abfA genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly abfA- dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with abfA -cluster-carrying B. longum , but not an abfA -deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, abfA -cluster abundance can predict FC, and transplantation of abfA cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial abfA cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies. [Display omitted] • abfA cluster-carrying B. longum strains ameliorate functional constipation (FC) • abfA abundance in the fecal microbiomes is predictive of FC in multiple cohorts • Introducing abfA enriches beneficial metabolites of gut residents (e.g., acetate) • abfA cluster is a gut-microbiome therapeutic target for FC in humans Zhang et al. show that B. longum strains possessing the abfA cluster can ameliorate functional constipation (FC) through enhanced arabinan utilization in the gut. Administration of abfA cluster-carrying B. longum -enriched arabinan utilization residents and beneficial metabolites that alleviate FC in both mice and humans suggests therapeutic targets for FC. [ABSTRACT FROM AUTHOR]