Batatasin III alleviates slow transit constipation by regulating gut microbiota and inhibiting the NLRP3-IL-1β pathway.

Abstract

Slow transit constipation (STC) is a functional gastrointestinal disorder characterized by impaired intestinal motility, inflammatory responses, and gut microbiota dysbiosis. Batatasin III, a natural stilbene compound, has been demonstrated to exhibit anti-inflammatory and neuroprotective properties; however, its role in STC remains unclear. In this study, a loperamide-induced STC mouse model was established and treated with low and high doses of Batatasin III. The therapeutic effects were evaluated through general phenotypic observation, small intestinal transit rate measurement, hematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, immunofluorescence, and 16S rRNA sequencing. Furthermore, Spearman correlation analysis was conducted to investigate the relationships between the gut microbiota and inflammatory cytokines and neurotransmitters. Batatasin III significantly improved fecal parameters and intestinal transit rate in mice, restored colonic tissue structure, and modulated levels of neurotransmitters such as 5-hydroxytryptamine (5-HT) and substance P (SP). Additionally, it inhibited activation of the NLRP3-IL-1β signaling pathway and reduced the expression of pro-inflammatory cytokines. Gut microbiota sequencing revealed an increase in beneficial bacteria such as Parabacteroides and Faecalibaculum, alongside a decreased abundance of the pro-inflammatory Rikenellaceae. These microbial changes were significantly correlated with both inflammatory markers and neurotransmitter levels. Batatasin III alleviates STC-related symptoms by modulating the gut microbiota and inhibiting the NLRP3-IL-1β inflammatory pathway. Its therapeutic effects may be mediated through the microbiota-gut-brain axis (MGBA), highlighting its potential value as a novel therapeutic agent for the treatment of slow transit constipation.