<i>Lactobacillus fermentum</i> species ameliorate dextran sulfate sodium-induced colitis by regulating the immune response and altering gut microbiota

Abstract

We evaluated immunometabolic functions of novel <i>Lactobacillus fermentum</i> strains (KBL374 and KBL375) isolated from feces of healthy Koreans. The levels of inflammatory cytokines, such as interleukin (IL)-2, interferon-γ, IL-4, IL-13, and IL-17A, were decreased, and that of the anti-inflammatory cytokine IL-10 was increased, in human peripheral blood mononuclear cells (PBMCs) treated with the <i>L. fermentum</i> KBL374 or KBL375 strain. When these strains were orally administered to mice with dextran sulfate sodium (DSS)-induced colitis, both <i>L. fermentum</i> KBL374 and KBL375 showed beneficial effects on body weight, disease activity index score, colon length, cecal weight, and histological scores. Furthermore, both <i>L. fermentum</i> KBL374 and KBL375 modulated the innate immune response by improving gut barrier function and reducing leukocyte infiltration. Consistent with the PBMC data, both <i>L. fermentum</i> KBL374- and KBL375-treated DSS mice demonstrated decreased Th1-, Th2-, and Th17-related cytokine levels and increased IL-10 in the colon compared with the DSS control mice. Administration of <i>L. fermentum</i> KBL374 or KBL375 to mice increased the CD4+CD25+Foxp3+Treg cell population in mesenteric lymph nodes. Additionally, <i>L. fermentum</i> KBL374 or KBL375 administration reshaped and increased the diversity of the gut microbiota. In particular, <i>L. fermentum</i> KBL375 increased the abundance of beneficial microorganisms, such as <i>Lactobacillus</i> spp. and <i>Akkermansia</i> spp. Both <i>L. fermentum</i> KBL374 and KBL375 may alleviate inflammatory diseases, such as inflammatory bowel disease, in the gut by regulating immune responses and altering the composition of gut microbiota.