Gut metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA255176 | ENA |
REPOSITORIES: ENA
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Project description:Gut microbiome research is rapidly moving towards the functional characterization of the microbiota by means of shotgun meta-omics. Here, we selected a cohort of healthy subjects from an indigenous and monitored Sardinian population to analyze their gut microbiota using both shotgun metagenomics and shotgun metaproteomics. We found a considerable divergence between genetic potential and functional activity of the human healthy gut microbiota, in spite of a quite comparable taxonomic structure revealed by the two approaches. Investigation of inter-individual variability of taxonomic features revealed Bacteroides and Akkermansia as remarkably conserved and variable in abundance within the population, respectively. Firmicutes-driven butyrogenesis (mainly due to Faecalibacterium spp.) was shown to be the functional activity with the higher expression rate and the lower inter-individual variability in the study cohort, highlighting the key importance of the biosynthesis of this microbial by-product for the gut homeostasis. The taxon-specific contribution to functional activities and metabolic tasks was also examined, giving insights into the peculiar role of several gut microbiota members in carbohydrate metabolism (including polysaccharide degradation, glycan transport, glycolysis and short-chain fatty acid production). In conclusion, our results provide useful indications regarding the main functions actively exerted by the gut microbiota members of a healthy human cohort, and support metaproteomics as a valuable approach to investigate the functional role of the gut microbiota in health and disease.
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Project description:The gut microbiome plays a crucial role in modulating host health and disease. It serves as a vast reservoir of functional molecules that hold great potential for clinical applications. One specific area of interest is identifying anticancer peptides (ACPs) for innovative cancer therapies. However, ACPs discovery is hindered by a heavy reliance on experimental methodologies. To overcome this limitation, we here employed a novel approach by leveraging the overlap between ACPs and antimicrobial peptides (AMPs). By combining well-established AMP prediction methods with mining techniques in metagenomic cohorts, a total of 40 potential ACPs is identified. Out of the identified ACPs, 39 demonstrated inhibitory effects against at least one cancer cell line, exhibiting significant differences from known ACPs. Moreover, the therapeutic potential of the two most promising peptides in a mouse xenograft cancer model is evaluated. Encouragingly, the peptides exhibit effective tumor inhibition without any detectable toxic effects. Interestingly, both peptides display uncommon secondary structures, highlighting its distinctive characteristics. This findings highlight the efficacy of the multi-center mining approach, which effectively uncovers novel ACPs from the gut microbiome. This approach has significant implications for expanding treatment options not only for CRC, but also for other cancer types.
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