Project description:Many previous studies had revealed that gastrointestinal microbiome is changed compositionally and ecologically in patients with colorectal cancer comparing with healthy population. These finding provide us with a new sight to take advantage of gut microbiota. The current study aims to explore new potential biomarkers for early screening and prognostic prediction of colorectal cancer and colorectal polyps by analyzing metagenomics and metabolomics of gut microbiota.
Project description:Urolithins are a class of bioactive metabolites derived from the metabolism of dietary ellagitannins by the human gut microbiota. In the gut, urolithins are dehydroxylated regioselectively based on microbiota composition and activity. A single 9-hydroxy urolithin dehydroxylase (ucd) operon in gut resident Enterocloster species has been described to date; however, most enzymes in the urolithin metabolic pathway remain uncharacterized. Here, we investigate urolithin cross-feeding between members of the gut microbiota and discover a novel urolithin dehydroxylase in a subset of Enterocloster species. We show that urolithin intermediates, released by gut resident Gordonibacter species during ellagic acid metabolism, are dehydroxylated at both the 9- and 10-positions by E. asparagiformis, E. citroniae, and E. pacaense, but not E. bolteae. Using untargeted proteomics, we uncover a 10-hydroxy urolithin dehydroxylase operon, termed uxd, responsible for these species-specific differences in urolithin metabolism. By inducing uxd expression with diverse urolithins, we show that 9-hydroxy urolithins are required for uxd transcription and 10-position dehydroxylation. Collectively, this study reveals some of the genes, proteins, and substrate features underlying differences in urolithin metabolism by the human gut microbiota.
Project description:By fermenting dietary fiber, the gut microbiota supplies carbon to host epithelial cells in the form of short-chain fatty acids and other metabolic byproducts. To track the transfer of carbon from fiber to host tissues via the microbiota and more clearly define the molecules mediating this transfer, we conducted stable isotope tracing in mice with U-13C-labeled inulin followed by untargeted metabolomics by LC-MS. Additionally, we applied this labeling approach to mice with chemically induced colitis to examine how inflammation impacts carbon transfer from the microbiota to host tissues, which may aid in understanding the development of inflammatory bowel diseases.
Project description:Rationale: Physical exercise is essential for skeletal integrity and bone health. The gut microbiome, as a pivotal modulator of overall physiologic states, is closely associated with skeletal homeostasis and bone metabolism. However, the potential role of intestinal microbiota in the exercise-mediated bone gain remains unclear. Methods: We conducted microbiota depletion and fecal microbiota transplantation (FMT) in ovariectomy (OVX) mice and aged mice to investigate whether the transfer of gut ecological traits could confer the exercise-induced bone protective effects. The study analyzed the gut microbiota and metabolic profiles via 16S rRNA gene sequencing and LC-MS untargeted metabolomics to identify key microbial communities and metabolites responsible for bone protection. Transcriptome sequencing and RNA interference were employed to explore the molecular mechanisms. Results: We found that gut microbiota depletion hindered the osteogenic benefits of exercise, and FMT from exercised osteoporotic mice effectively mitigated osteopenia. Comprehensive profiling of the microbiome and metabolome revealed that the exercise-matched FMT reshaped intestinal microecology and metabolic landscape. Notably, alterations in bile acid metabolism, specifically the enrichment of taurine and ursodeoxycholic acid, mediated the protective effects on bone mass. Mechanistically, FMT from exercised mice activated the apelin signaling pathway and restored the bone-fat balance in recipient MSCs. Conclusion: Our study underscored the important role of the microbiota-metabolic axis in the exercise-mediated bone gain, heralding a potential breakthrough in the treatment of osteoporosis.