Project description:Nlrp12-/- mice host a dysbiotic microbiome. After performing bone marrow transplantation study, we found mice receiving Nlrp12-/- haematopoitic cells pheno-copied the dysbiotic microbiome in the Nlrp12-/- mice.
Project description:We investigated the diversity of the primary sequences of the 16S rRNA genes among 46 commensal Neisseria strains and evaluated the use of this approach as a molecular typing tool in comparison with PFGE analysis. Identification to the genus was done using conventional methods and API NH (bio-Mérieux® ). Identification to species level was based on 16S rRNA gene sequencing. PFGE analysis was done using SpeI. Fourteen, two, three and fourteen 16S rRNA sequence types were found among twenty Neisseria flavescens, two Neisseria sicca, five Neisseria macacae and nineteen Neisseria mucosa clinical isolates. Forty-three different PFGE patterns were found among the tested strains. We demonstrated a high diversity among 16S rRNA genes which was reflected by PFGE analysis.
Project description:Inflammatory bowel disease (IBD) is linked to elevated cardiovascular risk, but the mechanisms connecting gut dysbiosis to heart pathology are unclear. This study investigated whether transplanting a dysbiotic microbiome (DM) from colitic mice could alter cardiac function in germ-free recipients. Results showed that DM transplantation impaired cardiac contractility and increased collagen deposition, indicating fibrosis. Transcriptomic analysis revealed widespread gene upregulation, particularly in females, with enrichment in histone acetylation and immune signaling pathways. Key epigenetic regulators, Nat8f7 and Tet1, were significantly upregulated, leading to increased histone acetylation and reduced DNA methylation at the Bcl11b promoter. This enhanced RNA polymerase II recruitment and Bcl11b transcription. In a model of dextran sodium sulfate (DSS)-induced colitis, similar upregulation of Nat8f7, Tet1, and Bcl11b occurred alongside increased fibrotic markers. Crucially, fecal microbiota transplantation from healthy donors reversed these molecular and fibrotic changes, normalizing Bcl11b expression and epigenetic status. Furthermore, functional assays demonstrated that BCL11B overexpression drives fibroblast proliferation and collagen production. In conclusion, these findings identify a novel gut-heart axis where a dysbiotic microbiome promotes cardiac fibrosis through the epigenetic activation of Bcl11b, and restoring a healthy microbiome mitigates these effects, pointing to microbiome-targeted strategies as potential therapies for IBD-related cardiovascular complications.
Project description:Background: NLRP12 is a cytosolic pattern recognition receptor in the family of NOD-like receptor. NLRP12 has been shown to suppress colorectal tumorigenesis. However, the precise mechansim of NLRP12-mediated regualtion of colorectal cancer is unknown. Results: RNAseq data demonstrate higher expression of oncogenes, matrix degrading enzymes such as matrix metaloproteinases (MMPs), and genes involved in tumor invasion in Nlrp12-/- compared to wild-type tumors. Notably, several of the genes highly induced in Nlrp12-/- tumors are regulated by the Wnt/b-catenin pathway. Conclusion: NLRP12 negatively regualtes the Wnt/b-catenin pathway to suppress colorectal cancer progression and invasion.
Project description:Transcriptional profiling of intestinal response to Citrobacter rodentium in wild-type and Nlrp12-deficient mice Four-conditions experiment, Nlrp12-deficient mouse infected by Citrobacter rodentium at day 7 versus non-infected Nlrp12-deficient mice with two biologicals replicates , Wild-type mouse infected by Citrobacter rodentium at day 7 versus non-infected Wild-type mice with two biologicals replicates and Nlrp12-deficient mouse infected by Citrobacter rodentium versus Control mouse infected by Citrobacter rodentium at 2 differents times ( day 0 and post infection at day 7 ) with three biologicals replicates