| Popis: |
Despite the association of the human gut microbiome and various diseases, a systematic definition of what constitutes a healthy human gut microbiome has not been established. This is crucial for microbiome research as it provides a basis for evaluating whether a given microbiome sample may deviate from the homeostasis state and is thus prone to the development of chronic diseases. This work aims to propose one such definition by using species/strain-resolved Genome-scale (GEM) models of metabolism. More specifically, we have constructed sample-specific GEMs from 30 healthy subjects using the taxonomic profiling of fecal metagenomic samples. We then computationally simulated these GEMs under a relevant diet (a supplemented typical Western diet) to determine which microbes in each sample contribute to the production of 17 key metabolites curated from literature and reported to be produced and secreted by the gut microbiota of healthy subjects. Beyond this pilot study, we plan to expand our analyses by creating samples-specific GEMs for a large-scale database of all publicly available metagenomic data from healthy subjects (~2,500 samples so far). We will additionally identify a core set of microbial species/strains that are necessary to perform all essential functions of a healthy microbiome. Taken together, this project offers a new paradigm to establish a healthy baseline microbiome definition by identifying generalized and personalized microbial blueprints that could serve as viable markers of health. |
