Project description:This work investigates the effects of a prebiotic mix containing lutein, zeaxanthin, and saffron, recognized for their anti-inflammatory properties, on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients.
Project description:ObjectiveContrary to the long-standing prerequisite of inducing selective (i.e. bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide microbiota shifts. Yet, a comprehensive characterization of this process is still lacking. Here, we apply 16S rDNA microbiota profiling and matching (GC-MS) metabolomics to assess the consequences of inulin fermentation both on the composition of the colon bacterial ecosystem and fecal metabolites profiles.DesignFecal samples collected during a double blind, randomized, cross-over intervention study (NCT02548247) set up to assess the effect of inulin consumption on stool frequency in healthy adults with mild constipation were analyzed. Fecal microbiota composition and metabolite profiles were linked to the study’s clinical outcome as well as to quality-of-life measurements recorded.ResultsWhile fecal metabolite profiles were not significantly altered by inulin consumption, our analyses did detect a modest effect on global microbiota composition. At the same time, specific inulin-induced changes in relative abundances of Anaerostipes, Bilophila, and Bifidobacterium were identified. The observed decrease in Bilophila abundances following inulin consumption was associated with both softer stools and a favorable change in constipation-specific quality of life measures.ConclusionsEcosystem-wide analysis of the effect of a dietary intervention with prebiotic inulin-type fructans on the colon microbiota revealed that this effect is specifically associated to three genera, one of which (Bilophila) representing a promising novel target for mechanistic research.
Project description:In animal models of inflammation and in farm animals, dietary inclusion of spray-dried porcine plasma (SDP) reduces mucosal inflammation. Here, we study whether these effects could be mediated by changes in the intestinal microbiota and if these changes are similar to those induced by oral antibiotics. Weaned 21-day-old C57BL/6 mice were divided into 3 groups: the CTL group, fed the control diet; the COL group, administered low doses of neomycin and colistin; and the SDP group, supplemented with 8% SDP. After 14 days, analysis of the fecal microbiome showed that the microbiota profiles induced by SDP and the antibiotics were very different, thus, SDP has prebiotic rather than antibiotic effects. At the phylum level, SDP stimulated the presence of Firmicutes, considerably increasing the lactobacilli population. It also enhanced the growth of species involved in regulatory T-lymphocyte homeostasis and restoration of the mucosal barrier, as well as species negatively correlated with expression of pro-inflammatory cytokines. At the mucosal level, expression of toll-like receptors Tlr2, Tlr4 and Tlr9, and mucous-related genes Muc2 and Tff3 with regulatory and barrier stability functions, were increased. SDP also increased expression of Il-10 and Tgf-β, as well as markers of macrophages and dendritic cells eventually promoting an immune-tolerant environment.
Project description:Background: Parkinson’s disease is associated with a dysbiotic, proinflammatory gut microbiome, disruptions to intestinal barrier functions, and immunological imbalance. Microbiota-produced short-chain fatty acids, such as propionic and butyric acid promote gut barrier integrity and immune regulation, but their impact on Parkinson’s disease pathology remains mostly unknown .Methods: In a randomized double-blind prospective study, 72 people with Parkinson’s disease received propionic and butyric acid and/or the prebiotic fiber 2′-fucosyllactose supplementation over 6 months in combination with existing Parkinson’s disease-specific therapy. Patients underwent complete neurological assessment and provided blood and stool samples before as well as 3 and 6 months after supplementation. Results: We observed improvement in motor and nonmotor symptoms, in addition to modulation of peripheral immunity and improved mitochondrial respiration in immunocytes. Postintervention microbiota remodeled inflammatory and barrier-related gene sets in gut organ cultures and improved in vitro barrier functions. Treatment response was associated with microbiome composition, distinct patterns of colonic transcription and permeability ex vivo. Multiobjective analysis revealed immune parameters associated with an optimal response to supplementation. Conclusion: Short-chain fatty acids ameliorate clinical symptoms in Parkinson’s disease patients and modulate intestinal and peripheral immunity.
Project description:Background: Parkinson’s disease is associated with a dysbiotic, proinflammatory gut microbiome, disruptions to intestinal barrier functions, and immunological imbalance. Microbiota-produced short-chain fatty acids, such as propionic and butyric acid promote gut barrier integrity and immune regulation, but their impact on Parkinson’s disease pathology remains mostly unknown .Methods: In a randomized double-blind prospective study, 72 people with Parkinson’s disease received propionic and butyric acid and/or the prebiotic fiber 2′-fucosyllactose supplementation over 6 months in combination with existing Parkinson’s disease-specific therapy. Patients underwent complete neurological assessment and provided blood and stool samples before as well as 3 and 6 months after supplementation. Results: We observed improvement in motor and nonmotor symptoms, in addition to modulation of peripheral immunity and improved mitochondrial respiration in immunocytes. Postintervention microbiota remodeled inflammatory and barrier-related gene sets in gut organ cultures and improved in vitro barrier functions. Treatment response was associated with microbiome composition, distinct patterns of colonic transcription and permeability ex vivo. Multiobjective analysis revealed immune parameters associated with an optimal response to supplementation. Conclusion: Short-chain fatty acids ameliorate clinical symptoms in Parkinson’s disease patients and modulate intestinal and peripheral immunity.
Project description:We have shown previously that prebiotic (Bimuno galacto-oligosacharides, B-GOS®) administration to neonatal rats increased hippocampal NMDAR proteins. The present study has investigated the effects of postnatal B-GOS® supplementation on hippocampus-dependent behavior in young, adolescent, and adult rats and applied electrophysiological, metabolomic and metagenomic analyses to explore potential underlying mechanisms. The administration of B-GOS® to suckling, but not post-weaned, rats reduced anxious behavior until adulthood. Neonatal prebiotic intake also reduced the fast decay component of hippocampal NMDAR currents, altered age-specific trajectories of the brain, intestinal, and liver metabolomes, and reduced abundance of fecal Enterococcus and Dorea bacteria. Our data are the first to show that prebiotic administration to rats during a specific postnatal period has long-term effects on behavior and hippocampal physiology. The study also suggests that early-life prebiotic intake may affect host brain function through the reduction of stress-related gut bacteria rather than increasing the proliferation of beneficial microbes.
Project description:BackgroundThere are complex interactions between aging, frailty, diet, and the gut microbiota; modulation of the gut microbiota by diet could lead to healthier aging. The purpose of this study was to test the effect of diets differing in sugar, fat, and fiber content upon the gut microbiota of mice humanized with microbiota from healthy or frail older people. We also performed a 6-month dietary fiber supplementation in three human cohorts representing three distinct life-stages.MethodsMice were colonized with human microbiota and then underwent an 8-week dietary intervention with either a high-fiber/low-fat diet typical of elderly community dwellers or a low-fiber/high-fat diet typical of long-stay residential care subjects. A cross-over design was used where the diets were switched after 4 weeks to the other diet type to identify responsive taxa and innate immunity changes. In the human intervention, the subjects supplemented their normal diet with a mix of five prebiotics (wheat dextrin, resistant starch, polydextrose, soluble corn fiber, and galactooligo-saccharide) at 10 g/day combined total, for healthy subjects and 20 g/day for frail subjects, or placebo (10 g/day maltodextrin) for 26 weeks. The gut microbiota was profiled and immune responses were assayed by T cell markers in mice, and serum cytokines in humans.ResultsHumanized mice maintained gut microbiota types reflecting the respective healthy or frail human donor. Changes in abundance of specific taxa occurred with the diet switch. In mice with the community type microbiota, the observed differences reflected compositions previously associated with higher frailty. The dominance of Prevotella present initially in community inoculated mice was replaced by Bacteroides, Alistipes, and Oscillibacter. Frail type microbiota showed a differential effect on innate immune markers in both conventional and germ-free mice, but a moderate number of taxonomic changes occurring upon diet switch with an increase in abundance of Parabacteroides, Blautia, Clostridium cluster IV, and Phascolarctobacterium. In the human intervention, prebiotic supplementation did not drive any global changes in alpha- or beta-diversity, but the abundance of certain bacterial taxa, particularly Ruminococcaceae (Clostridium cluster IV), Parabacteroides, Phascolarctobacterium, increased, and levels of the chemokine CXCL11 were significantly lower in the frail elderly group, but increased during the wash-out period.ConclusionsSwitching to a nutritionally poorer diet has a profound effect on the microbiota in mouse models, with changes in the gut microbiota from healthy donors reflecting previously observed differences between elderly frail and non-frail individuals. However, the frailty-associated gut microbiota did not reciprocally switch to a younger healthy-subject like state, and supplementation with prebiotics was associated with fewer detected effects in humans than diet adjustment in animal models.
Project description:in the present study, we evaluated whether microbiota modulation is able to restore hepatic steatosis induced by n-3 PUFA depletion in mice. For this purpose, mice were fed during three months with a n-3 PUFA-depleted diet (presenting a high n-6/n-3 PUFA ratio), and then supplemented with fructooligosaccharides (FOS, 0.25g/day/mice), a prebiotic, during the last ten days of the experiment (DEF/FOS). In the same time, some n-3 PUFA-depleted mice were returned on a control diet during the last 10 days of treatment (DEF/CT) to compare the effect of FOS supplementation to a restored intake in n-3 PUFA. Microarray analyses were performed to identify the molecular targets modified by FOS supplementation in the liver of n-3 PUFA depleted mice. These mice were compared to control mice (fed a control diet during the 112 days of experiment) and to n-3 PUFA-depleted mice (fed a n-3 PUFA-depleted diet during the 112 days of experiment) for which the results have been previously published (Pachikian B.D. et al. PLoS One. 2011;6(8):e23365, accession number GSE26986)
Project description:Dysregulation of microbiota gut-retina axis in neovascular age-related macular degeneration: beneficial ocular effects of a lutein, zeaxanthin and saffron based prebiotic supplementation