Project description:<p>Synbiotics may modulate gut microbiota and prevent infections. In a randomized controlled trial (NCT01625273) infants weaned from breast milk were fed formula with prebiotics (fructo- and galactooligosaccharides) or the same prebiotic formula with <em>Lactobacillus paracasei ssp. paracasei</em> strain F19 (synbiotics) from 1 until 6 months of age. The objective was to examine synbiotic effects on gut microbiota maturation. Fecal samples collected at ages 1, 4, 6 and 12 months (324 samples for microbial and 197 samples for metabolic characterization) were analyzed. We demonstrate enrichment of Bifidobacterium and increases in antimicrobial metabolites derived from microbial fermentation of phenylalanine and pectins in the synbiotic group. The gut microbiota of infants with lower respiratory tract infections (LRTI) were depleted of Lactobacillales but enriched in Klebsiella species and associated antimicrobial resistance genes. These compositional and functional changes of the gut microbiota may be linked to the previously reported reduction of LRTI in the synbiotic group.</p>
Project description:Asthma is multi-factorial disorder, and microbial dysbiosis enhances lung inflammation and asthma-related symptoms. Probiotics has shown anti-inflammatory effect and could regulate the gut-lung axis. Thus, a three-month randomized, double-blind, and placebo-controlled human trial was performed to investigate the adjunctive efficacy of probiotics in managing asthma.
Project description:A genome-wide RNA expression study based on a Phase II randomized placebo-controlled clinical trial of topiramate (TPM) treatment of methamphetamine (METH) dependence. Gene expression data were analyzed based on TPM responses at Weeks 8 and 12, to identify differentially expressed genes and related pathways.
Project description:Animal and epidemiological studies suggest that lycopene and fish oil may modify the risk or delay progression of prostate cancer, however, the molecular mechanisms involved are poorly understood. We examined the effects of these micronutrients on prostate gene expression in a double-blind placebo-controlled randomized clinical trial (Molecular Effects of Nutritional Supplements, MENS).
Project description:Obesity and overweight are closely related to diet, and gut microbiota play an important role in body weight and human health. The aim of this study was to explore how Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 supplementation alleviate obesity by modulating the human gut microbiome. A randomized, double-blind, placebo-controlled study was conducted on 72 overweight individuals. Over a 12-week period, probiotic groups consumed 5×10^9 colony-forming units of HY7601 and KY1032), whereas the placebo group consumed the same product without probiotics. After treatment, the probiotic group displayed a reduction in body weight (p <0.001), visceral fat mass (p <0.025), and waist circumference (p <0.007), and an increase in adiponectin (p <0.046), compared with the placebo group. Additionally, HY7601 and KY1032 supplementation modulated bacterial gut microbiota characteristics and beta diversity by increasing Bifidobacteriaceae and Akkermansiaceae, and decreasing Prevotellaceae and Selenomonadaceae. In summary, HY7601 and KY1032 probiotics exert anti-obesity effects by regulating the gut microbiota; hence, they have therapeutic potential for preventing or alleviating obesity and overweight.
Project description:In this open-label randomized controlled phase I/II trial, 20 stable peritoneal dialysis patients underwent two 4 h dwells with acidic glucose-based PDF, with and without 8 mM alanyl-glutamine (AlaGln) in a cross-over design. Unsupervised hierarchical clustering of transcriptomics data suggested specific effects of AlaGln in patients who had previously suffered from peritonitis.
Project description:We profiled genome-wide gene expression in nasal scrapes following grass pollen challenge and Prednisone treatment. It was a randomized, double-blind, placebo-controlled, three-period, cross-over trial to evaluate the effects of single oral doses of 10 mg and 25 mg of prednisone on inflammatory mediators measured in nasal exudates after nasal allergen challenge in susceptible individuals with allergic rhinitis. It examined the ability to quantify responses to allergen challenge and resolve dose responsive treatment effects of prednisone.
Project description:PD-1/PD-L1 blockade did not show survival benefit in high grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial and by combining RNA-seq and multiplexed immunofluorescence stainings, we explored the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment and identified parameters correlating to response. 1) The combination therapy resulted in a significant increase of intraepithelial CD8+PD-1+ T cells that correlated to clinical benefit. 2) High CD8B/FOXP3 and high CD8B/ENTPD1 ratios were significantly associated with response to NACT+P, while KDR and VEGFR2 expression were associated with resistance. 3) Combining endothelial and monocyte signatures and the CD8B/FOXP3 ratio predicted response to NACT+P with an AUC of 0.93 (95% CI 0.84–1.00). These results indicate that targeting regulatory T cells and endothelial cells, especially VEGFR2+ endothelial cells, could overcome ovarian cancer immune resistance.
