Immune-enhancing effect of Weizmannia coagulans BCG44 and its supernatant on cyclophosphamide-induced immunosuppressed mice and RAW264.7 cells via the modulation of the gut microbiota.

Abstract

We established a model of cyclophosphamide (CTX)-induced immunosuppressed mice and RAW264.7 cells to assess the effectiveness of W. coagulans BCG44 and its supernatant in enhancing immune function and modulating the gut microbiota. W. coagulans BCG44 and its supernatant restored Th17/Treg balance and alleviated gut inflammation by elevating the expression of interleukin-10 (IL-10) and decreasing IL-6 and toll-like receptor 4 (TLR4). Meanwhile, W. coagulans BCG44 and its supernatant downregulated the levels of lipopolysaccharide and D-lactic acid while increasing the expression of tight junction proteins (ZO-1 and occludin) and goblet cells/crypts to ameliorate mucosal damage. W. coagulans BCG44 and its supernatant may restore the gut microbiota in the immunosuppressed mice by regulating keystone species (Lactobacillus and Lachnospiraceae). PICRUSt2 function prediction and BugBase analysis showed thatW. coagulansBCG44 and its supernatant significantly down-regulated American trypanosomiasis and potentially_pathogenic. In addition, under normal versus inflamed culture conditions, stimulation of RAW246.7 cells with W. coagulans BCG44 supernatant activated immune response with increasing proliferation ability and the gene expression of IL-10 while decreasing TLR4. Metabolites in the W. coagulans BCG44 supernatant included arginine, tyrosine, solamargine, tryptophan, D-mannose, phenyllactic acid, and arachidonic acid. Collectively, these findings suggested that W. coagulans BCG44 and its supernatant possess potential immunomodulatory activity and modulate gut microbiota dysbiosis in the CTX-induced immunosuppressed mice.