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

Abstract

We evaluated immunometabolic functions of novel Lactobacillus fermentum 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 antiinflammatory cytokine IL-10 was increased, in human peripheral blood mononuclear cells (PBMCs) treated with the L. fermentum KBL374 or KBL375 strain. When these strains were orally administered to mice with dextran sulfate sodium (DSS)-induced colitis, both L. fermentum KBL374 and KBL375 showed beneficial effects on body weight, disease activity index score, colon length, cecal weight, and histological scores. Furthermore, both L. fermentum KBL374 and KBL375 modulated the innate immune response by improving gut barrier function and reducing leukocyte infiltration. Consistent with the PBMC data, both L. fermentum 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 L. fermentum KBL374 or KBL375 to mice increased the CD4+CD25+Foxp3+Treg cell population in mesenteric lymph nodes. Additionally, L. fermentum KBL374 or KBL375 administration reshaped and increased the diversity of the gut microbiota. In particular, L. fermentum KBL375 increased the abundance of beneficial microorganisms, such as Lactobacillus spp. and Akkermansia spp. Both L. fermentum 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.

Prior Toxoplasma Gondii Infection Ameliorates Liver Fibrosis Induced by Schistosoma Japonicum through Inhibiting Th2 Response and Improving Balance of Intestinal Flora in Mice

“…Co-infection may have a reciprocal regulatory effect on Th1 and Th2 responses. Whether Th cells differentiate into Th1 or Th2 on initial stage is interactively regulated by cytokines and other factors [6]. We showed that infection with schistosomiasis alone significantly increased the levels of IFN-γ and IL-4 in the host serum, while pre-infection with toxoplasma further improved the increasing effect of IFN-γ and soluble worm antigen (SWA)-IgG2a level but decreased the level of IL-4 and anti-soluble egg antigen (SEA)-IgG1.…”

“…Recent studies have shown that CD4 + T cell response plays a key role in the development of liver fibrosis. The polarization of T helper (Th) cell type 1/Th2 response and their immunoregulation are closely related to the occurrence and development of schistosomiasis-induced hepatic fibrosis [4][5][6][7][8][9][10].…”

Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract

“…Further, FMT significantly increases MHC-II-dependent secretion of IL-10 by CD4 + T cells and is useful for the treatment of experimental colitis, while also reducing the ability of dendritic cells, monocytes, and macrophages to present MHC-II-dependent bacterial antigens to colonic T cells (14). For example, Lactobacillus fermentum reduces the levels of proinflammatory cytokines, such as IL-2, IFN-γ, IL-4, IL-13, and IL-17A, while increasing levels of anti-inflammatory cytokines, such as IL-10, to relieve symptoms of inflammatory bowel disease (118). Further, FMT alleviates antibiotic-related depletion of IL-33 during colonic inflammation caused by Clostridium difficile (117).…”

The Influence of Reactive Oxygen Species in the Immune System and Pathogenesis of Multiple Sclerosis

“…Inhibition of ROS sources via the utilization of antioxidants leads to increased IFN- γ production in T cells, promoting Th1-mediated immune responses. Hence, increased levels of ROS triggered to promote both IL-4 and IL-2 production in T cells lead to T-cell differentiation towards the Th2 phenotype [ 86 , 97 ]. Several studies have mentioned the important role of Nrf2 in the activation and differentiation of T cells.…”