Jia wei Coix Fuzi Baijiang Powder, a traditional Chinese medicine, alleviates sepsis-induced intestinal injury by regulating the metabolite profile of intestinal microbiota

Sepsis causes intestinal mucosal injury, bacterial translocation, and worsening of intestinal and distant organ injury. The intestinal injury further aggravates sepsis. Jia wei Coix Fuzi Baijiang Powder (JCM), a traditional Chinese medicine, effectively alleviated sepsis-induced intestinal injury in our clinical study. We collected fecal samples from patients with sepsis who were treated or not with JCM. Intestinal flora 16sRNA sequencing and intestinal metabonomic analysis revealed that integrated JCM + conventional treatment considerably elevated the content of GMDG3 PE (0:0/14:0) in the peripheral blood of patients with sepsis. In vitro and in vivo experiments revealed that GMDG3 may inhibit inflammation, enhance the expression of intestinal tight junction protein, and perform a protective function against sepsis-induced damage to the intestinal barrier. Label-free proteomic analysis of samples from lipopolysaccharide (LPS)-Caco-2 and LPS-Caco-2 + GMDG3 groups revealed significant differences in aryl hydrocarbon receptor repressor (AHR) levels between the two groups. The co-immunoprecipitation assay showed a direct interaction between AHR and GMDG3. In vitro studies also revealed that GMDG3 could activate AHR. In an LPS-induced Caco-2 cell model, we discovered that KynA could activate AHR, inhibit the MLCK-pMLC signal pathway, and elevate the expression level of tight junction protein within intestinal epithelial cells.