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

Abstract

<p>Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics such as <em>Bifidobacteria</em> can improve this bowel disorder, yet efficacy is strain-dependent. We determine that a genetic factor, the <em>abfA</em> cluster governing arabinan utilization, in <em>Bifidobacterium longum</em> impacts treatment efficacy against functional constipation (FC). In mice with FC, <em>B. longum,</em> but not an <em>abfA</em> mutant, improved gastrointestinal transit time, effects that were dependent upon dietary arabinan. <em>abfA </em>genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly <em>abfA-</em>dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with <em>abfA</em>-cluster-carrying <em>B. longum,</em> but not an <em>abfA</em>-deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, <em>abfA</em>-cluster abundance can predict FC and transplantation of <em>abfA</em> cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial <em>abfA</em> cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies.<br></p>