Jianchang No. 1 (1) formula alleviates irritable bowel syndrome with diarrhea improving gut microbiota and regulating toll-like receptors/nuclear factor-kappa B signaling pathway in bowel syndrome with diarrhea rats.

OBJECTIVETo evaluate the therapeutic efficacy of Jianchang No. 1 (1) in treating irritable bowel syndrome with diarrhea (IBS-D) and to explore its underlying mechanisms of action.

METHODSIBS-D rat models were established through a combination of chronic restraint stress, water avoidance stress, and the administration of senna decoction. Body weight, fecal water content (FWC), and intestinal capacity threshold in IBS-D rats were monitored before and after treatment. Pathological alterations in colon tissue were examined using hematoxylin and eosin staining. Serum levels of lipopolysaccharide (LPS), along with LPS content in colon tissue were measured using the enzyme-linked immunosorbent assay. 16S rRNA sequencing technology was employed to assess the abundance and compositional shifts within the gut microbiota. Quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence were employed to determine gene and protein expression in colonic samples.

RESULTSJianchang No. 1 treatment restored body weight, lowered FWC, and raised the intestinal capacity threshold in IBS-D rats. Meanwhile, Jianchang No. 1 enhanced both the richness and composition of the gut microbiota. Moreover, Jianchang No. 1 markedly upregulated the tight-junction proteins zonula occludens-1 and occludin together with the anti-inflammatory cytokine interleukin-10, while simultaneously downregulating the LPS-toll-like receptor (TLR) 2/4- myeloid differentiation factor 88- nuclear factor kappa B (NF-κB) axis and the downstream pro-inflammatory mediators interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, together with interleukin-4 and interferon-gamma.

CONCLUSIONSJianchang No. 1 maintains intestinal barrier integrity by reshaping gut-microbial diversity and composition, dampening the TLR/NF-κB signaling cascade, and thereby alleviating low-grade colonic inflammation and its attendant clinical symptoms in IBS-D rats.