Project description:Gemcitabine treatment shifts the intestinal microbiota of PC mice towards an inflammatory profile which may worsen mucositis and side effects observed upon chemotherapy. We explored the effect of a specific probiotics blend administered, with or without gemcitabine treatment, to PC xenografted mice.
Project description:FastQ files from 16S sequencing of fecal samples from pancreatic cancer xenografted mice not treated (CTRL) and treated with chemotherapy (GEM+nab-PTX), probiotics (PRO) and chemotherapy + probiotics (GEM+nab-PTX+PRO)
Project description:Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-wk bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1-/Δ7 mice, which have a median lifespan of ~20wk, and their wild-type littermates. The colonic barrier in Ercc1-/Δ7 mice was characterized by a thin (<10µm) mucus layer. L. plantarum prevented this decline in mucus integrity in Ercc1-/Δ7 mice, whereas B. breve exacerbated it. Bacterial supplementations affected the expression of immune-related genes, including Toll-like receptor 4. Regulatory T cell frequencies were increased in the mesenteric lymph nodes of L. plantarum- and L. casei-treated Ercc1-/Δ7 mice. L. plantarum- and L. casei-treated Ercc1-/Δ7 mice showed increased specific antibody production in a T cell-dependent immune response in vivo. By contrast, the effects of bacterial supplementation on wild-type control mice were negligible. Thus, supplementation with L. plantarum – but not with L. casei and B. breve – prevented the decline in the mucus barrier in Ercc1-/Δ7 mice. Our data indicate that age is an important factor influencing beneficial or detrimental effects of candidate probiotics. These findings also highlight the need for caution in translating beneficial effects of probiotics observed in young animals or humans to the elderly.
Project description:Probiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function via largely unknown molecular mechanisms. To explore in vivo mucosal responses of healthy adults to probiotics, we obtained transcriptomes in an intervention study following a double-blind placebo-controlled cross-over design. In the mucosa of the proximal small intestine of healthy volunteers, probiotic strains from the species Lactobacillus acidophilus, L. casei and L. rhamnosus each induced differential gene regulatory networks and pathways in the human mucosa. Comprehensive analyses revealed that these transcriptional networks regulate major basal mucosal processes, and uncovered remarkable similarity to response profiles obtained for specific bioactive molecules and drugs. This study elucidates how intestinal mucosa of healthy humans perceive different probiotics and provides avenues for rationally designed tests of clinical applications. Keywords: mucosal response of healthy adult humans to lactic acid bacteria
Project description:Probiotics have shown promise in positively altering gut microbiota and can potentially improve the gut flora of individuals with obesity. Recently, the development of probiotics with “Pharmabiotic” properties, which can reduce body fat and inhibit lipid accumulation, has emerged as a notable approach for effectively combating obesity. Nevertheless, owing to the lack of a universal methodology for elucidating the molecular mechanisms of probiotics, their antiobesity effects remain largely unknown. Herein, we developed an advanced multiomics-based strategy to decipher the mechanisms by which probiotics and their derivatives curtail adipocyte lipid production to affirm their antiobesity potential. Our initial investigation assessed the impact of probiotics and their derivatives on adipocyte differentiation and lipid generation at defined differentiation stages. Leveraging these insights, we performed comprehensive multiomics analyses at selected intervals to deepen our understanding regarding the suppression mechanisms of lipid formation. This framework confirmed the antiobesity efficacy of Lactobacillus reuteri lysate, targeting early differentiation to impede branched-chain amino acid (BCAA) catabolism and reduce adipocyte lipid accumulation. Specifically, L. reuteri lysate suppressed Krüppel-like factor 5 expression in early adipocyte differentiation phases, downregulating peroxisome proliferator–activated receptor gamma expression and reducing BCAA catabolism. Concurrently, L. reuteri lysate enhanced hypoxia-inducible factor 1 alpha expression, consequently downregulating lipin-1 expression in initial adipocyte differentiation stages, thus inhibiting adipogenesis. This study underscores the efficacy of our strategy in elucidating the intricate causal dynamics between host and microbiome, advancing therapeutic development and target exploration of probiotics.
Project description:Analysis of differentiated Caco-2 intestinal epithelial cell line cocultured with probiotics L. acidophilus NCFM™, B. lactis 420, L. salivarius Ls-33 bacterial cells or treated with cell-free supernatant, and with E. coli O157:H7 cell-free supernatant. Lactobacillus and Bifidobacterium are important genera suggested to be beneficial for human health and E. coli O157:H7 is a pathogen causing hemorrhagic colitis and hemolytic uremic syndrome. Results provide insight into the mechanisms underlying the beneficial effects of probiotics on intestinal epithelial cells and a comparison to pathogenic E. coli.
Project description:The pharmacological significance of B vitamins, essential for various metabolic processes, and the therapeutic potential of probiotics in gastrointestinal health have been well-documented. However, the interactions between these entities remain poorly understood. In this study, we endeavored to elucidate the potential interplay between B vitamins and probiotics utilizing liquid chromatography-triple quadrupole mass spectrometry, pharmacokinetic modeling, and 16S rRNA gene sequencing. Employing healthy and pseudo-germ-free rat models, we revealed that probiotics significantly improve the absorption of B1, B3, B5, and B12, and that the gut microbiota played a mediating role in this enhanced absorption of B vitamins by probiotics. High-throughput genetic sequencing uncovered a synergistic effect of B vitamins and probiotics in modulating the gut microbiota, particularly increasing the abundance of Verrucomicrobia and Akkermansia. Furthermore, in vitro experiments demonstrated that probiotics used in this study had a relatively minor influence on the production and permeability of B vitamins, while B vitamins did not significantly contribute to the growth, auto-aggregation, and adhesion of probiotics. In summary, a complex network connection exists between B vitamins and probiotics, wherein the gut microbiota emerges as a pivotal factor that cannot be overlooked.