Project description:Synbiotics are a combination of probiotics and prebiotics which can alter the composition of the gastrointestinal tract evoking beneficial effects throughout the body through the production of a battery of bioactive metabolites. In this study, a synbiotic was used to reduce the behavioral and biochemical symptoms of depression and this nanostring panel was used to decipher where along the gut-brain-axis the synbiotic-derived metabolites were invoking their beneficial effects on the immune system. The synbitoic was composed of two probiotic bacteria (Lactobacillus fermentum ATCC 793 and Bifidobacteria longum ATCC 15707 and a grape -derived prebiotic composed of grape seed polyphenol extract, resveratrol and a concord grape extract. Male mice (C57BL/6) were pretreatment with either nothing (control), BDPP, probiotic or synbiotic and underwent 28 days of chronic unpredicitable stress. After 28 days, animals' behavior reflected an increase in depressive- and anxiety-like behavior, rescued specifically by the synbiotic. This nanostring multiplex analysis reveals both tissue- and treatment-specific effects on immune modulators.
Project description:Host-microbiome-dietary interactions play crucial roles in regulating human health, yet direct functional assessment of their interplays, cross-regulations and downstream disease impacts remains challenging. We adopted metagenome-informed metaproteomics (MIM), in both mice and humans, to simultaneously explore host, dietary, and species-level microbiome interactions across diverse scenarios, including commensal and pathogen colonization, nutritional modifications, and antibiotic-induced perturbations. Implementation of MIM in murine auto-inflammation and in human IBD characterized a ‘compositional dysbiosis’ and a concomitant, species-specific ‘functional dysbiosis’ driven by suppressed commensal responses to inflammatory host signals. Microbiome transfers unraveled early-onset kinetics of these host-commensal cross-responsive patterns, while predictive analyses identified candidate fecal host-microbiome IBD biomarker protein pairs outperforming S100A8/S100A9 (calprotectin). Importantly, a simultaneous fecal nutrient assessment enabled determination of IBD-related consumption patterns, dietary treatment compliance and small-intestinal digestive aberrations. Collectively, a parallelized dietary-bacterial-host MIM assessment functionally uncovers trans-kingdom interactomes shaping gastrointestinal ecology, while offering personalized diagnostic and therapeutic insights into microbiome-associated disease.
Project description:Host-microbiome-dietary interactions play crucial roles in regulating human health, yet direct functional assessment of their interplays, cross-regulations and downstream disease impacts remains challenging. We adopted metagenome-informed metaproteomics (MIM), in both mice and humans, to simultaneously explore host, dietary, and species-level microbiome interactions across diverse scenarios, including commensal and pathogen colonization, nutritional modifications, and antibiotic-induced perturbations. Implementation of MIM in murine auto-inflammation and in human IBD characterized a ‘compositional dysbiosis’ and a concomitant, species-specific ‘functional dysbiosis’ driven by suppressed commensal responses to inflammatory host signals. Microbiome transfers unraveled early-onset kinetics of these host-commensal cross-responsive patterns, while predictive analyses identified candidate fecal host-microbiome IBD biomarker protein pairs outperforming S100A8/S100A9 (calprotectin). Importantly, a simultaneous fecal nutrient assessment enabled determination of IBD-related consumption patterns, dietary treatment compliance and small-intestinal digestive aberrations. Collectively, a parallelized dietary-bacterial-host MIM assessment functionally uncovers trans-kingdom interactomes shaping gastrointestinal ecology, while offering personalized diagnostic and therapeutic insights into microbiome-associated disease.