Project description:Recent studies demonstrate that the gut mycobiota plays a key role in several tumors’ development. However, the contribution of commensal fungi to prostate cancer initiation and progression remains understudied. Here, we find that Nakaseomyces glabratus (N.glabratus), is enriched in fecal, blood, and tumor samples of a subset of CRPC patients, positively correlating with patients’ poor overall survival. Oral administration of N.glabratus to castrated mice accelerated CRPC development by controlling polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, androgen deprivation therapy (ADT) increases intestinal permeability, resulting in the leakage of N.glabratus from the gut to the tumor site, where it activates PMN-MDSCs by binding to the Dectin-2 receptor. Treatment of mice with a negatively charged hydrogel blocks N.glabratus translocation to the tumor site, reducing PMN-MDSCs intratumoral infiltration and activation. Taken together, these findings reveal that the gut-to-tumor translocation of commensal fungi contributes to endocrine resistance in CRPC by enhancing the immunosuppressive microenvironment of these tumors.
Project description:Roots of Arabidopsis thaliana do not engage in symbiotic association with mycorrhizal fungi but host taxonomically diverse fungal communities that influence health and disease states. We sequenced the genomes of 41 isolates representative of the A. thaliana root mycobiota for comparative analysis with 79 other plant-associated fungi. We report that root mycobiota members evolved from ancestors having diverse lifestyles and retained diverse repertoires of plant cell wall-degrading enzymes (PCWDEs) and effector-like small secreted proteins. We identified a set of 84 gene families predicting best endophytism, including families encoding PCWDEs acting on xylan (GH10) and cellulose (AA9). These genes also belong to a core transcriptional response induced by phylogenetically-distant mycobiota members in A. thaliana roots. Recolonization experiments with individual fungi indicated that strains with detrimental effects in mono-association with the host not only colonize roots more aggressively than those with beneficial activities but also dominate in natural root samples. We identified and validated the pectin degrading enzyme family PL1_7 as a key component linking aggressiveness of endophytic colonization to plant health.
Project description:We found that low protein diet consumption resulted in decrease in the percentage of normal Paneth cell population in wild type mice, indicating that low protein diet could negatively affect Paneth cell function. We performed fecal microbiota composition profiling. Male mice were used at 4-5 weeks of age. Fecal samples were collected for microbiome analysis.
Project description:We found that western diet consumption resulted in decrease in the percentage of normal Paneth cell population in wild type mice, indicating that western diet could negatively affect Paneth cell function. Subsequent generations of western diet consumption further reduced percentages of normal Paneth cell population. We performed fecal microbiota composition profiling. Male mice were used at 4-5 weeks of age. Fecal samples were collected for microbiome analysis.