Bacillus subtilis R-179 combined with Enterococcus faecium R-026 alleviate antibiotic-associated diarrhea by...

Although probiotics are known to be effective against antibiotic-associated diarrhea (AAD), it remains unclear how they regulate gut microbiota and resistance genes to exert this effect. This study investigated the effects of live combined Bacillus subtilis R-179 and Enterococcus faecium R-026 (LCBE) on AAD, gut microbiota and resistance genes in C57BL/6 mice. Twenty-four male C57BL/6 mice were divided into three groups. The M and LCBE groups were administered 0.2 mL of antibiotics (550 mg.kg^-1 amoxicillin, 450 mg.kg^-1 clindamycin, and 400 mg.kg^-1 streptomycin) twice a day for twenty-five consecutive days. The N group was provided normal saline. After successful modeling, the LCBE group was gavaged with LCBE at a dose of 0.02 g/mice/day for nine days. LCBE significantly improved multiple diarrhea-related parameters, reduced the levels of lipopolysaccharides, TLR4, and IL-6, increased the levels of IL-10, Occludin, and ZO-1, and alleviated inflammatory infiltration and mucosal damage. It increased the abundances of Bifidobacterium_pseudolongum and Lactobacillus_johnsonii, and decreased the abundances of [Clostridium]_innocuum, Clostridioides_difficile, and Klebsiella_pneumoniae. Furthermore, it reduced the levels of various resistance genes, including APH (3'')-Ib, QnrS1, sul1, and sul2, increased the levels of betaine and indoxyl sulfate, and decreased the levels of 4-chlorophenyl and taurocholic acid. During the treatment of AAD, LCBE alleviated inflammation, repaired intestinal damage, modulated the composition of gut microbiota and expression of drug resistance genes, and improved serum metabolism in the treatment of antibiotic-associated diarrhea. These findings underscore the potential therapeutic significance of LCBE as a multi-target agent to manage AAD.