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.
Project description:A time-series alteration in fecal microbiota was linked to the emergence of intraepithelial bacteria and a unique transcriptome profile in the mouse colon during IBD development.
Project description:We report the RNAseq data from captive common marmosets with gastrointestinal diseases housed at MIT. Samples were collected at necropsy from the duodenum and jejunum from 3 animals presenting with intestinal bowel disease (IBD) and 3 animals with duodenal strictures/ulcers. To determine the transcriptomic profile of animals with strictures, we evaluated the duodenal tissue immediately adjacent to the stricture lesion and compared it to the duodenum of non-stricture (IBD) animals as a non-stricture control. To determine the transcriptomic profile of animals with IBD, we evaluated the jejunum of animals with IBD with the jejunum of non-IBD (stricture) animals as a non-IBD control. Minimal pathology was observed in the non-IBD control but enteritis was noted in non-stricture controls. We report that stricture may affect the intestinal absorption and lipid metabolism in marmosets, while IBD increases immune responses.