Probiotics have been reported to ameliorate symptoms of type 2 diabetes mellitus (T2DM) in animal models and human studies. We previously demonstrated that oral administration of Lactobacillus reuteri ADR-3 reduced insulin resistance in high-fructose-fed (HFD) rats. In the present study, we first identified another L. reuteri strain, ADR-1, which displayed anti-diabetes activity that reduced the levels of serum HbA1c and cholesterol and that increased antioxidant proteins in HFD rats. We further performed a randomized, double-blinded, placebo-controlled trial with a total of 68 T2DM patients to examine the beneficial effects of oral consumption of L. reuteri strains ADR-1 and ADR-3 and to investigate the associated changes in intestinal flora using a quantitative PCR method to analyze 16 S rRNA in fecal specimens. Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group (n = 22) after 3 months of intake when compared with those in the placebo group (n = 22). Although there was no significant difference in the HbA1c serum level among participants who consumed heat-killed ADR-3 (n = 24), the systolic blood pressure and mean blood pressure were significantly decreased after 6 months of intake. There was no obvious change in serum inflammatory cytokines or antioxidant proteins in participants after intaking ADR-1 or ADR-3, except for a reduction in IL-1β in the ADR-3 consumption group after 6 months of intake. With the analysis of fecal microflora, we found that L. reuteri or Bifidobacterium spp. were significantly increased in the ADR-1 and ADR-3 consumption groups, respectively, after 6 months of intake. Interestingly, a significant reduction in HbA1c was observed in the ADR-1 and ADR-3 consumption participants who displayed at least an 8-fold increase in fecal L. reuteri. We also observed that there was a significantly positive correlation between Bifidobacterium spp. and Lactobacillus spp. in participants with increased levels of fecal L. reuteri. In the ADR-1 intake group, the fecal Lactobacillus spp. level displayed a positive correlation with Bifidobacterium spp. but was negatively correlated with Bacteroidetes. The total level of fecal L. reuteri in participants in the ADR-3 consumption group was positively correlated with Firmicutes. In conclusion, L. reuteri strains ADR-1 and ADR-3 have beneficial effects on T2DM patients, and the consumption of different strains of L. reuteri may influence changes in intestinal flora, which may lead to different outcomes after probiotic intake.

Psoriasis, which is regarded as a T-cell-mediated chronic inflammatory skin disease, is characterized by hyperproliferation and poor differentiation of epidermal keratinocytes. In this study, we aimed to determine the in vivo effect of a potentially probiotic strain, Lactobacillus pentosus GMNL-77, in imiquimod-induced epidermal hyperplasia and psoriasis-like skin inflammation in BALB/c mice. Oral administration of L. pentosus GMNL-77 significantly decreased erythematous scaling lesions. Real-time polymerase chain reaction showed that treatment with L. pentosus GMNL-77 significantly decreased the mRNA levels of proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-6, and the IL-23/IL-17A axis-associated cytokines (IL-23, IL-17A/F, and IL-22) in the skin of imiquimod-treated mice. In addition, we found that L. pentosus GMNL-77 decreased the spleen weights of the imiquimod-treated group and reduced the numbers of IL-17- and IL-22-producing CD4 T cells in the spleen. In conclusion, the present study provides insight into the potential use of L. pentosus GMNL-77 in the future treatment of psoriasis.

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Probiotics are defined as microorganisms with beneficial health effects when consumed by humans, being applied mainly to improve allergic or intestinal diseases. Due to the increasing resistance of pathogens to antibiotics, the abuse of antibiotics becomes inefficient in the skin and in systemic infections, and probiotics may also provide the protective effect for repairing the healing of infected cutaneous wounds. Here we selected two Lactobacillus strains, L. plantarum GMNL-6 and L. paracasei GMNL-653, in heat-killed format to examine the beneficial effect in skin wound repair through the selection by promoting collagen synthesis in Hs68 fibroblast cells. The coverage of gels containing heat-killed GMNL-6 or GMNL-653 on the mouse tail with experimental wounds displayed healing promoting effects with promoting of metalloproteinase-1 expression at the early phase and reduced excessive fibrosis accumulation and deposition in the later tail-skin recovery stage. More importantly, lipoteichoic acid, the major component of Lactobacillus cell wall, from GMNL-6/GMNL-653 could achieve the anti-fibrogenic benefit similar to the heat-killed bacteria cells in the TGF-β stimulated Hs68 fibroblast cell model. Our study offers a new therapeutic potential of the heat-killed format of Lactobacillus as an alternative approach to treating skin healing disorders.

Osteoporosis is a metabolic inflammatory disease, an imbalance occurs between bone resorption and formation, leading to bone loss. Anti-inflammatory diet is considered having the potential to ameliorate osteoporosis. Heat-killed probiotics exhibit health benefits in relation to their immunomodulatory effects, but the detail mechanism involved in gut microbiota balance, host metabolism, immunity, and bone homeostasis remains unclear. In this study, we evaluated the antiosteoporotic effects of heat-killed Lacticaseibacillus paracasei GMNL-653 in vitro and in ovariectomized (OVX) mice. Furthermore, whole-genome sequencing and comparative genomics analysis demonstrated potentially genes involved in antiosteoporotic activity. The GMNL-653 exerts anti-inflammatory activity which restored gut microbiota dysbiosis and maintained intestinal barrier integrity in the OVX mice. The levels of IL-17 and LPS in the sera decreased following GMNL-653 treatment compared with those of the vehicle control; mRNA levels of RANKL were reduced and TGF-β and IL-10 enhanced in OVX-tibia tissue after treatment. The levels of IL-17 were significantly associated with gut microbiota dysbiosis. Gut microbial metagenomes were further analyzed by PICRUSt functional prediction, which reveal that GMNL-653 intervention influence in several host metabolic pathways. The analysis of whole-genome sequencing accompanied by comparative genomics on three L. paracasei strains revealed a set of GMNL-653 genes that are potentially involved in antiosteoporotic activity. Our findings validated antiosteoporotic activity of heat-killed GMNL-653 using in vitro and in vivo models, to whole-genome sequencing and identifying genes potentially involved in this gut microbiota–bone axis.