マウスモデルにおける細菌およびエンドトキシン誘発敗血症に対する異なるプロバイオティクス株の防御的役割の評価

Sepsis caused by Gram-negative bacteria such as Escherichia coli and Salmonella enterica is a major contributor to global morbidity and mortality. This study investigated the protective effects of four human milk-derived probiotic strains, Staphylococcus hominis, Staphylococcus epidermidis, Streptococcus salivarius, and Streptococcus lactarius, in murine models of pathogen- and lipopolysaccharide (LPS)-induced sepsis. Mice received probiotic pre-treatment before challenge with LPS, E. coli, or Salmonella enterica typhimurium. Clinical signs, survival, body weight, gross and histopathological lesions, serum biochemical markers, fecal bacterial load, and intestinal cytokine gene expression (TNF-α, IL-6) were recorded. Pathogen- and LPS-challenged groups showed high mortality, significant weight loss, marked intestinal pathology, elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine, increased fecal pathogen counts, and upregulated TNF-α and IL-6 expression. Probiotic pre-treatment improved survival, preserved body weight, reduced lesion severity, normalized biochemical parameters, lowered fecal pathogen load, and downregulated pro-inflammatory cytokines. Among the tested strains, Strep. lactarius provided the most consistent protection in E. coli and LPS models, whereas Strep. Salivarius was most effective against Salmonella-induced sepsis. The results indicate that specific human milk-derived probiotics can reduce systemic inflammation and organ injury in Gram-negative bacterial sepsis.