Project description:Background: Probiotic-like bacteria treatment has been described to be associated with gut microbiota modifications. Goal: To decipher if the effects of the tested probiotic-like bacteria are due to the bacteria itself or due to the effects of the bacteria on the gut microbiota. Methodology: In this study, gut microbiota has been analyzed from feces samples of subjects with metabolic syndrome and treated with one of the 2 tested probiotic-like bacteria or with the placebo during 3months.
Project description:Interventions: The probiotic is Escherichia coli Nissle 1917 (EcN), supplied as Mutaflor, Ardeypharm. Each tablet contains at least 5x108 colony forming units (CFU) EcN.
Participants will take either 2 tablets of probiotic or placebo (sugar pill) per day for 14 to 28 days, prior to surgery or colonoscopy. Previous studies have administered probiotic for 28 days. This has been shown to be a safe human dose in earlier phase I trials that unfortunately did not measure colonisation as an end-point. The duration of intervention will depend upon the time participants are consented before their procedure (at least 14 days).
Adherence of the intervention will be monitored by probiotic tablet return.
Mutaflor and placebo tablets are provided for free from Ardeypharm.
Primary outcome(s): Neoplastic colonisation as assessed by DNA sequencing of surplus pathology tissue.[5 years post-enrolment.]
Study Design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Bio-availability
Project description:The dataset is composed of 62 samples (31 subjects before and after probiotic-like bacteria treatment). Sequencing was performed using Illumina HiSeq 2500. Fastq files are provided.
Project description:To understand transcriptional regulation of probiotic bacteria under acidic condition, RNAseq analysis was carried out over different growth conditions
Project description:Probiotic bacteria may render mice resistant to the development of various inflammatory and infectious diseases. This study aimed to identify underlying mechanisms by which probiotic bacteria may influence intestinal immune homeostasis in non-inflammatory conditions. To this end, we studied the effect of short term (3 days) and long term (28 days) oral administration of VSL#3, a mixture of 8 probiotic bacteria, to healthy BALB/c and C57BL/6 mice, with dominant humoral or cellular immunity, respectively. Long-term treatment with VSL#3 resulted in an increase of B cells and a decrease of CD4+ T cells in the Peyer’s patches (PP) and mesenteric lymph nodes (MLN) of both mouse strains, compared to untreated mice. However, genome wide gene expression profiling using micro-arrays revealed that prolonged administration of VSL#3 to BALB/c and C57BL/6 mice was associated with host-specific modulation of gene expression in colon and small intestine. Whereas VSL#3 treatment resulted in down-regulation of Il13 and Epx, and up-regulation of Il12rb1, Ccr5, Cxcr3 and Cxcl10 in BALB/c mice, such effects were not observed in C57BL/6 mice. In BALB/c mice, a 2-fold increase in CD103+ CD11c+ dendritic cells was found both in PP and in MLN, 18 hours after the first treatment with VSL#3. Prolonged treatment with VSL#3 was associated with increased numbers of Th17 cells and Foxp3+ regulatory T cells in the MLN of these mice. In conclusion, these experiments in healthy mice show that probiotic bacteria may alter the immunological phenotype of the host; the nature of these effects is dependent on mouse strain. In conclusion, these experiments in healthy mice show that probiotic bacteria may alter the immunological phenotype of the host; the nature of these effects is dependent on mouse strain.
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:Leptosphaeria maculans, causal agent of stem canker disease, colonises oilseed rape (Brassica napus) in two stages: a short and early colonisation stage corresponding to cotyledon or leaf colonisation, and a late colonisation stage during which the fungus colonises systemically and symptomlessly the plant during several months before stem canker appears. To date, determinants of the late colonisation stage are poorly understood; L. maculans may either successfully escape plant defences leading to the stem canker development, or the plant can develop an “adult-stage” resistance reducing canker incidence. To get insight into these determinants, we performed an RNA-seq pilot project comparing fungal gene expression in infected cotyledons and in symptomless and necrotic stems. Despite the low fraction of fungal material in infected stems, enough fungal transcripts were detected and a large portion of fungal genes were expressed, thus validating the feasibility of the approach. Our analysis showed that all avirulence genes previously identified are under-expressed during stem colonisation compared to cotyledon colonisation. A validation RNA-seq experiment was then done to investigate the expression of candidate effector genes during systemic colonisation. 307 "late" effector candidates, under-expressed in the early colonisation stage and over-expressed in the infected stems, were identified. Finally our analysis revealed a link between regulation of expression of effectors and their genomic location: the late effector candidates, putatively involved in the systemic colonisation, are located in gene-rich genomic regions, whereas the "early" effector genes, over-expressed in the early colonisation stage, are located in gene-poor regions of the genome.
Project description:Probiotic bacteria may render mice resistant to the development of various inflammatory and infectious diseases. This study aimed to identify underlying mechanisms by which probiotic bacteria may influence intestinal immune homeostasis in non-inflammatory conditions. To this end, we studied the effect of short term (3 days) and long term (28 days) oral administration of VSL#3, a mixture of 8 probiotic bacteria, to healthy BALB/c and C57BL/6 mice, with dominant humoral or cellular immunity, respectively. Long-term treatment with VSL#3 resulted in an increase of B cells and a decrease of CD4+ T cells in the Peyer’s patches (PP) and mesenteric lymph nodes (MLN) of both mouse strains, compared to untreated mice. However, genome wide gene expression profiling using micro-arrays revealed that prolonged administration of VSL#3 to BALB/c and C57BL/6 mice was associated with host-specific modulation of gene expression in colon and small intestine. Whereas VSL#3 treatment resulted in down-regulation of Il13 and Epx, and up-regulation of Il12rb1, Ccr5, Cxcr3 and Cxcl10 in BALB/c mice, such effects were not observed in C57BL/6 mice. In BALB/c mice, a 2-fold increase in CD103+ CD11c+ dendritic cells was found both in PP and in MLN, 18 hours after the first treatment with VSL#3. Prolonged treatment with VSL#3 was associated with increased numbers of Th17 cells and Foxp3+ regulatory T cells in the MLN of these mice. In conclusion, these experiments in healthy mice show that probiotic bacteria may alter the immunological phenotype of the host; the nature of these effects is dependent on mouse strain. In conclusion, these experiments in healthy mice show that probiotic bacteria may alter the immunological phenotype of the host; the nature of these effects is dependent on mouse strain. 40 samples (4 experimental groups, 5 biological replicates), performed in two inbred mice strains