Traditional Mongolian medicine Batri-7 exhibits chemopreventive activity in colitis-associated colorectal cancer through microbiota modulation and NLRP3 inflammasome targeting.

[ETHNOPHARMACOLOGICAL RELEVANCE] Batri-7 (BT-7) is a compound herbal remedy rooted in traditional Mongolian medicine (TMM), composed of seven medicinal plants. Historically, it has been prescribed to treat various gastrointestinal conditions, including chronic enteritis and ulcerative colitis. However, despite this long-standing use in managing inflammatory disorders of the gut, the preventive effects of BT-7 on colitis-associated colorectal cancer (CAC), as well as its underlying molecular mechanisms, remains incompletely elucidated.

[AIM OF THE STUDY] This study aimed to assess the therapeutic efficacy of BT-7 in an AOM/DSS-induced murine model of CAC, while also investigating its modulatory effects on systemic inflammation, intestinal barrier function, gut microbiota dynamics, and inflammation-related molecular signaling pathways.

[MATERIALS AND METHODS] A chemically induced CAC model was established in C57BL/6 mice using azoxymethane (AOM) and dextran sodium sulfate (DSS). BT-7 was then administered orally at three dosage levels, and therapeutic outcomes were evaluated through a range of methods:clinical scoring, serum biochemical analysis, histological analysis, immunohistochemistry, and gut microbial profiling via 16S rRNA sequencing. To explore the underlying mechanistic pathways, with a particular focus on inflammasome regulation, transcriptome sequencing, quantitative PCR, and Western blotting were employed.

[RESULTS] BT-7 treatment was well-tolerated, with no evidence of liver or kidney toxicity. Mice receiving BT-7 exhibited improved body weight maintenance, lower disease activity scores, and preserved colon length. Histologically, there was substantial restoration of mucosal architecture and reduced epithelial hyperplasia, alongside significant suppression of tumor formation. Systemically, BT-7 reduced levels of key pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and KC/GRO) and enhanced intestinal barrier integrity, as evidenced by the elevation of Occludin and ZO-1. Additionally, BT-7 decreased the abundance of pro-inflammatory taxa, such as Bacteroidota, and enriched beneficial genera like Lactobacillus and Dubosiella. The increased relative abundance of Lactobacillus_johnsonii and decreased Lactobacillus _murinus highlighted the probiotic effects of BT-7. Functional pathway prediction revealed that BT-7's microbiota was enriched in pathways related to carbohydrate and amino acid metabolism, as well as digestive system and immune-related functions. Transcriptomic analysis revealed downregulation of inflammatory signaling, particularly within the NOD-like receptor pathway, with reduced NLRP3 expression at both mRNA and protein levels confirming this effect.

[CONCLUSIONS] This work demonstrates that BT-7 exerts protective effects against CAC by suppressing inflammation, improving epithelial integrity, and restoring microbial homeostasis. Mechanistically, the NLRP3 inflammasome is identified as BT-7's primary target in this context, which aligns with its traditional use in treating gastrointestinal disorders. Collectively, these findings highlight BT-7's therapeutic potential as a chemopreventive agent, supporting its utility in aiding inflammation-associated colorectal cancer treatment.