Wheat-Grain Moxibustion Ameliorates Ulcerative Colitis: Suppressing Intestinal Inflammation, Modulating Gut Microbiota, and Restoring Mucosal Barrier Integrity.

Wheat-grain moxibustion (Wgm), a specialized form of moxibustion therapy, exerts therapeutic effects by delivering thermal stimulation from ignited moxa wool to specific acupoints, thereby preventing or treating various diseases. Previous studies have demonstrated its beneficial role in ulcerative colitis (UC); however, the exact mechanisms involved remain to be elucidated. This study investigated the therapeutic effects of Wgm at Zhongwan (CV12), Tianshu (ST25), and Shangjuxu (ST37) sites on colonic inflammatory cytokines, intestinal mucosal barrier homeostasis, and gut microbiome profiles in UC mice. A DSS-induced UC mouse model was established and Wgm at Zhongwan (CV12), Tianshu (ST25), and Shangjuxu (ST37) acupoints was conducted once a day for 7 consecutive days. The therapeutic effects of Wgm were assessed by monitoring body weight variations, disease activity index (DAI) scoring, colon length measurements, and histopathological features of colonic tissues, and the expression levels of inflammatory cytokines and intestinal mucosal barrier-related factors in colonic tissues were measured using enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), Western blotting (WB), and real-time quantitative polymerase chain reaction (RT-PCR). Additionally, 16S rRNA sequencing was performed to characterize the gut microbial community structure and diversity. Wgm applied to Zhongwan (CV12), Tianshu (ST25), and Shangjuxu (ST37) significantly reduced the DAI and histological scores of colonic tissue in UC mice, while demonstrating specific efficacy in increasing body weight and colon length. By inhibiting the TLR4/MyD88/NF-κB signaling pathway, Wgm suppressed the release of intestinal inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, MPO, and COX2), downregulated intestinal injury markers (DAO, D-LA, ICAM-1, and IFABP), and upregulated mucosal barrier proteins (MUC2, ZO-1, Occludin, Claudin 1), thereby restoring intestinal mucosal barrier function and restoring the composition and diversity of the gut microbiota. Our results suggest that Wgm alleviates colitis by suppressing the TLR4/MyD88/NF-κB signaling pathway, reducing pro-inflammatory cytokine release, restoring intestinal mucosal barrier integrity, and modulating gut microbiome profiles. These findings collectively elucidate the potential therapeutic mechanisms by which Wgm ameliorates UC pathogenesis and demonstrate its multimodal regulatory effects in UC.