Gut commensal Parabacteroides goldsteinii protects against Salmonella infection in mice by enhancing innate defense function

Bacterial enteritis caused by the invasion of Salmonella enterica subsp. enterica serovar Typhimurium into the intestinal epithelium is often associated with the overactivation of the immune system, production of proinflammatory cytokines, disruption of the intestinal barrier and dysbiosis of gut microbiota. In this study, the gut commensal Parabacteroides goldsteinii isolated from the feces of mice and enriched after consumption of Hirsutella sinensis mycelium (HSM) was selected to evaluate its ameliorative effect on enteritis. S. typhimurium was used to establish an enteritis model in mice and the effects of orally administered heat-killed P. goldsteinii were evaluated. The results indicated that P. goldsteinii reduced the systemic burdens of S. typhimurium, restored mucosal barrier integrity, decreased overexpression of genes involved in inflammation, and modulated the composition of gut microbiota, leading to the amelioration of enteritis. A subsequent transcriptomic study in germ-free mice highlighted that P. goldsteinii administration increased the expression of α-defensins, Reg3g, lyz1, and CARD9, which are involved in mucosal defense mechanisms. The increased expression of these factors was validated in infected specific-pathogen free (SPF) mice. The results indicated that P. goldsteinii may enhance intestinal immunity, leading to a reduction in S. typhimurium pathogenicity. P. goldsteinii may be developed as a food supplement for the amelioration of S. typhimurium infection-associated enteritis.