Project description:The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease pathogenesis has been difficult due to the apparent disconnect between animal and human studies and a lack of an integrated multi-omics view in the context of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases.
Project description:This is the first report of the metabolic and metaproteomic integrated changes in the gut and liver by the swallowed periodontopathogen. Periodontal disease pathogen Porphyromonas gingivalis are observed in faeces as peptides level in proteomic analysis and make changes in bowel microbial composition in db/db mouse. Orally Periodontal disease pathogen throwing as experimental periodontal disease model make gluconeogenesis in db/db mouse liver and hyperglycemia. Multi-omics analysis reveal Pg decreasing in energy metabolism and glucagon store in db/db mouse liver. These findings suggest that periodontal treatment improving oral microbiota can make diabetic hyperglycemia ameliorate in liver and support these diabetes treatments credibly.
Project description:Background: Vascular cognitive impairment and dementia (VCID) represents a spectrum of cognitive disorders linked to cerebrovascular pathology, yet its molecular underpinnings remain misunderstood. Methods: We conducted a multi-omics analysis of post-mortem brain tissue from the superior parietal lobe (Brodmann area 7) in 19 individuals with neuropathologically confirmed VCID and 21 age-matched controls. Whole genome sequencing, genome-wide DNA methylation profiling, transcriptomic analysis, and metabolomics profiling were performed to identify molecular signatures and integrated pathways involved in VCID pathogenesis. Results: Epigenome-wide association analysis revealed widespread hypermethylation in VCID, with significant enrichment of genes involved in the Rac/Rho GTPase cycle and cytoskeletal remodeling. Transcriptomic analysis confirmed dysregulation of small GTPase signaling, oxidative stress responses, and lipid metabolism. Metabolomic profiling identified altered levels of diacylglycerols (DAGs) and phosphatidylethanolamines (PEs), which showed strengthened associations with Rac/Rho pathway genes in VCID compared to controls. Conclusions: Our integrative multi-omics study identifies the Rac/Rho GTPase cycle as a convergent pathway disrupted at the genomic, epigenomic, transcriptomic, and metabolic levels in VCID. Lipid metabolism, particularly involving DAGs and PEs, emerged as a key downstream effector contributing to VCID. These findings offer mechanistic insights into VCID pathogenesis and suggest lipid signaling pathways as promising therapeutic targets for intervention.
Project description:The comparative integrated multi-omics analysis identifies CA2 as a novel target for chordoma Running title: The integrated multi-omics analysis in chordoma
Project description:This study aimed to identify a biomarker predicting response to ustekinumab therapy. Therefore, we used transcriptomic data (colonic and ileal tissue, CD4 T-cell and CD14 monocytes), which we integrated through Multi-Omics Factor Analysis.
Project description:This study reveals the molecular mechanisms of liver metabolic dysregulation in ACE2 knockout (ACE2KO) mice through multi-omics analysis. ACE2 deficiency exacerbates lipid accumulation, disrupts RAS balance, and induces hepatocyte injury and inflammation. Integrated multi-omics analysis identified numerous differentially expressed genes, proteins, and metabolites, highlighting the PPAR signaling pathway as a central regulatory hub. ACE2 deletion also impairs detoxification and antioxidant balance, creating a self-reinforcing oxidative injury cycle. These findings provide new insights into the mechanisms and therapeutic targets of ACE2-related liver diseases.
