Comparative genomics reveals that Bifidobacterium longum subsp. longum BZG4 alleviates constipation in mice via synergistic xylooligosaccharide

Abstract

Constipation is a common gastrointestinal disorder that affects all age groups. Probiotics show efficacy in relieving constipation; however, their efficacy is highly strain-specific, and the genetic basis for this heterogeneity remains unclear. This study investigated the genetic determinants and underlying mechanisms of different Bifidobacterium longum subsp. longum strains in alleviating constipation. Among the three strains evaluated in loperamide-induced constipation mice, only BZG4 significantly alleviated constipation. Comparative genomic analysis revealed that a unique xylooligosaccharide (XOS) utilization cluster was only located in the chromosome in strain BZG4, which was further validated by its ability to grow with XOS as the sole carbon source. Synbiotic supplementation with BZG4 and XOS produced synergistic effects, evidenced by significant improvements in fecal water content, 5-h fecal pellet output, whole-gut transit time, and small intestinal propulsion rate. Mechanistically, the synbiotic BZG4-XOS alleviated constipation by modulating gut microbiota to increase the butyric acid level in feces, thereby restoring the integrity of the enteric nervous system, regulating the relevant neuromodulators and enhancing MUC2-dominated mucus and water secretion. These findings determined the strain-specific XOS cluster of BZG4 as a genetic basis for constipation relief and provided a genetic strategy for developing precision synbiotics targeting gastrointestinal motility disorders.