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

Zhang, C.; Yu, L.; Ma, C.; Jiang, S.; Wang, S.; Tian, F.; Xue, Y.; Zhao, J.; Zhang, H.; Liu, L.; Chen, W.; Huang, S.; Zhang, J.; Zhai, Q.

doi:10.1101/2022.12.15.518621

bioRxiv · 10.1101/2022.12.15.518621

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

Zhang, C.·Yu, L.·Ma, C.·Jiang, S.·Wang, S.·Tian, F.·Xue, Y.·Zhao, J.·Zhang, H.·Liu, L.·Chen, W.·Huang, S.·Zhang, J.·Zhai, Q.

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Abstract

Probiotics have been widely used to improve impaired gastro-intestinal motility, yet their efficacy varied substantially across strains. Here, by a large-scale genetic screen plus in vivo measurements, we identified a key genetic factor (abfA cluster governing arabinan utilization) in probiotic Bifidobacterium longum harnessing 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 exogenous abfA-cluster- carrying B. longum can well establish itself in the gut, and enrich arabinan-utilization residents and beneficial metabolites (e.g., acetate, butyrate, chenodeoxycholic acid and uracil). Finally, transplantation of abfA-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 microbial abfA cluster in ameliorating FC, establishing generalizable principles for developing functional-genomics-directed probiotic therapies.

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Zhang, C., Yu, L., Ma, C., Jiang, S., Wang, S., Tian, F., Xue, Y., Zhao, J., Zhang, H., Liu, L., Chen, W., Huang, S., Zhang, J., Zhai, Q.. 2022-12-15. Identification of a key genetic factor governing arabinan utilization in the gut microbiome suggests a novel therapeutic target for constipation. https://doi.org/10.1101/2022.12.15.518621

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