Preclinical evaluation of 6-Gingerol in modulating gut microbiota and SCFAs to mitigate -associated diarrhea in mice.

associated diarrhea (CDAD) is a growing healthcare concern with limited effective treatments. 6-Gingerol, a major bioactive compound in ginger, exhibits notable antibacterial and anti-inflammatory properties, making it a potential alternative therapy. This study combines and approaches to evaluate its efficacy against CDAD. assays determined the half-maximal inhibitory concentration (IC) and minimum inhibitory concentration (MIC) of 6-Gingerol against , which were 61.99 μM and 173.3 μM, respectively, indicating direct antibacterial activity. , a mouse model of CDAD was used to assess the therapeutic effects of 6-Gingerol. Outcomes included clinical symptoms, load, inflammation, intestinal barrier integrity, gut microbiota composition, and short-chain fatty acids (SCFAs) levels. The results showed that in the CDAD mouse model, high-dose 6-Gingerol significantly alleviated CDAD symptoms, reduced load ( < 0.001), improved gut barrier function, and suppressed intestinal inflammation. Although it did not notably increase microbial diversity, 6-Gingerol modulated gut microbiota structure-markedly increasing beneficial bacteria such as ( < 0.01) and , while reducing harmful bacteria including and . Targeted quantification revealed restored levels of key SCFAs, particularly acetate ( < 0.001), butyrate ( < 0.01), and valerate ( < 0.001), which are closely linked to gut health and recovery from CDAD. In summary, 6-Gingerol exerts therapeutic effects against CDAD through direct inhibition of , regulation of gut microbiota, restoration of SCFA levels, and protection of the intestinal barrier, highlighting its potential as a novel natural treatment for CDAD.