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.

L. acidophilus treatment can modulate immune responses, control the micro-RNA levels and restore the gut microbiota of mice with DSS-induced colitis. Therefore, L. acidophilus treatment could be useful to control inflammatory bowel diseases.

Administration of probiotics has been linked to immune regulation and changes in gut microbiota composition, with effects on atopic dermatitis (AD). In this study, we investigated amelioration of the symptoms of AD using Lactobacillus paracasei KBL382 isolated from the feces of healthy Koreans. Mice with Dermatophagoides farinae extract (DFE)-induced AD were fed 1 × 10 9 CFU d −1 of L. paracasei KBL382 for 4 weeks. Oral administration of L. paracasei KBL382 significantly reduced AD-associated skin lesions, epidermal thickening, serum levels of immunoglobulin E, and immune cell infiltration. L. paracasei KBL382-treated mice showed decreased production of T helper (Th)1-, Th2-, and Th17-type cytokines, including thymic stromal lymphopoietin, thymus, and activation-regulated chemokine, and macrophage-derived chemokine, and increased production of the anti-inflammatory cytokine IL-10 and transforming growth factor-β in skin tissue. Intake of L. paracasei KBL382 also increased the proportion of CD4+ CD25+ Foxp3+ regulatory T cells in mesenteric lymph nodes. In addition, administration of L. paracasei KBL382 dramatically changed the composition of gut microbiota in AD mice. Administration of KBL382 significantly ameliorates AD-like symptoms by regulating the immune response and altering the composition of gut microbiota.

Gut microbiota play an important role in immune responses and energy metabolism. In this study, we evaluated whether administration of Lactobacillus fermentum (L. fermentum) KBL375 isolated from healthy Korean feces improves the atopic dermatitis using the house dust mite (Dermatophagoides farinae)-induced atopic dermatitis (AD) mouse model. Administration of L. fermentum KBL375 significantly decreased dermatitis score, ear and dorsal thickness, and serum immunoglobulin E level in AD-induced mice. Significant reductions in mast cells and eosinophils were discovered in skin tissues from L. fermentum KBL375-treated mice. T helper 2 cell-related cytokines interleukin (IL)-4, IL-5, IL-13, and IL-31 significantly decreased, and anti-inflammatory cytokine IL-10 or transforming growth factor-β increased in skin tissues from L. fermentum KBL375-treated mice. In addition to phenotypic changes in skin tissues, L. fermentum KBL375 treatment induced an increase in the CD4+CD25+Foxp3+ cell population in mesenteric lymph nodes. Taxonomic and functional analyses of gut microbiota showed significantly higher cecum bacterial diversities and abundances including genus Bilophila, Dorea, and Dehalobacterium in L. fermentum KBL375-treated mice. Metabolic analysis of the cecum also showed significant changes in the levels of various amino acids including methionine, phenylalanine, serine, and tyrosine, as well as short chain fatty acids such as acetate, butyrate, and propionate in AD-induced mice due to L. fermentum KBL375 treatment. These altered metabolites in AD-induced mice returned to the levels similar to those in control mice when treated with L. fermentum KBL375. Therefore, L. fermentum KBL375 could be useful for AD treatment by modulating the immune system and inducing various metabolites.

Macrophage metabolic pathways show changes in response to various external stimuli. Especially, increased lipopolysaccharide, an important bacterial component and Toll-like receptor 4 agonist, can induce activity in various macrophage metabolic pathways, including energy production and biosynthesis, as well as high immune responses due to increase in differentiated M1 macrophages. In this study, we confirmed that Lactobacillus paracasei ( L. paracasei ) KBL382, KBL384 and KBL385, isolated from the feces of healthy Koreans, can modulate various enzymes and membrane transporters related to glycolysis or macrophage polarization including hypoxia-inducible factor 1-alpha (HIF1A), inducible nitric oxide synthase (iNOS) and arginase in stimulated macrophages at the mRNA level, using the in vitro rodent bone‐marrow‐derived macrophage (BMDM) model. All L. paracasei exhibited significant down-regulatory effects on mRNAs for glycolysis-related enzymes, including lactate dehydrogenase A, solute carrier family 2 member 1, and triosephosphate isomerase. Moreover, L. paracasei treatment could lead to significant reductions in HIF1A or iNOS mRNA, and induced arginase mRNA in the BMDM model. Therefore, further extensive studies should be performed to support the application of L. paracasei, such as in probiotics or therapeutics, in controlling abnormal immune responses related to macrophage.