Rhubarb extract ameliorates slow-transit constipation in rats by modulating gut microbiota and bile acid homeostasis

Rhubarb, the dried rhizome and root of Rheum species, is a traditional Chinese medicine widely used for constipation relief. However, the mechanisms underlying its therapeutic effects on slow-transit constipation (STC) remain unclear.

To investigate the therapeutic effects of rhubarb extract (RE) on STC rats and elucidate the underlying mechanisms using an integrated multi-omics approach.

The chemical constituents of RE were characterized by LC-MS. Network pharmacology and molecular docking were used to predict potential targets and pathways. An STC rat model was established using loperamide, and the effects of RE were evaluated by constipation-related phenotypes, intestinal transit, histopathology, inflammatory cytokines, and serum 5-hydroxytryptamine (5-HT). Additionally, 16S rRNA sequencing, untargeted metabolomics, and ELISA-based bile acid analysis were performed to investigate the regulatory effects of RE on gut microbiota and host metabolism.

RE markedly alleviated STC symptoms in rats, increasing intestinal transit rate from 40.5% to 79.5% and serum 5-HT levels from 2.43 to 5.81 μg/mL. Network pharmacology identified serotonergic synapse signaling as a key pathway. RE also partially restored gut microbiota dysbiosis and bile acid metabolic disturbances. Several bile acid-related metabolites were markedly altered in STC rats and partially normalized following RE treatment. ELISA analysis further indicated restoration of primary and secondary bile acid balance. Moreover, RE upregulated colonic TPH1 and TGR5 expression while downregulating SLC6A4, consistent with altered serotonergic signaling.

RE alleviates STC by improving intestinal motility, modulating gut microbiota composition, and restoring bile acid metabolic homeostasis.