Global compositional and functional states of the human gut microbiome in health and disease.

The human gut microbiota is of increasing interest, with metagenomics a key tool for analyzing bacterial diversity and functionality in health and disease. Despite increasing efforts to expand microbial gene catalogs and an increasing number of metagenome-assembled genomes, there have been few pan-metagenomic association studies and in-depth functional analyses across different geographies and diseases. Here, we explored 6014 human gut metagenome samples across 19 countries and 23 diseases by performing compositional, functional cluster, and integrative analyses. Using interpreted machine learning classification models and statistical methods, we identified Fusobacterium nucleatum and Anaerostipes hadrus with the highest frequencies, enriched and depleted, respectively, across different disease cohorts. Distinct functional distributions were observed in the gut microbiomes of both westernized and nonwesternized populations. These compositional and functional analyses are presented in the open-access Human Gut Microbiome Atlas, allowing for the exploration of the richness, disease, and regional signatures of the gut microbiota across different cohorts.

Genome-scale metabolic modelling of the human gut microbiome reveals changes in the glyoxylate and dicarboxylate metabolism in metabolic disorders.

The human gut microbiome has been associated with metabolic disorders including obesity, type 2 diabetes, and atherosclerosis. Understanding the contribution of microbiome metabolic changes is important for elucidating the role of gut bacteria in regulating metabolism. We used available metagenomics data from these metabolic disorders, together with genome-scale metabolic modeling of key bacteria in the individual and community-level to investigate the mechanistic role of the gut microbiome in metabolic diseases. Modeling predicted increased levels of glutamate consumption along with the production of ammonia, arginine, and proline in gut bacteria common across the disorders. Abundance profiles and network-dependent analysis identified the enrichment of tartrate dehydrogenase in the disorders. Moreover, independent plasma metabolite levels showed associations between metabolites including proline and tyrosine and an increased tartrate metabolism in healthy obese individuals. We, therefore, propose that an increased tartrate metabolism could be a significant mediator of the microbiome metabolic changes in metabolic disorders.

Disease, Drugs and Dysbiosis: Understanding Microbial Signatures in Metabolic Disease and Medical Interventions.

Since the discovery of the potential role for the gut microbiota in health and disease, many studies have gone on to report its impact in various pathologies. These studies have fuelled interest in the microbiome as a potential new target for treating disease Here, we reviewed the key metabolic diseases, obesity, type 2 diabetes and atherosclerosis and the role of the microbiome in their pathogenesis. In particular, we will discuss disease associated microbial dysbiosis; the shift in the microbiome caused by medical interventions and the altered metabolite levels between diseases and interventions. The microbial dysbiosis seen was compared between diseases including Crohn's disease and ulcerative colitis, non-alcoholic fatty liver disease, liver cirrhosis and neurodegenerative diseases, Alzheimer's and Parkinson's. This review highlights the commonalities and differences in dysbiosis of the gut between diseases, along with metabolite levels in metabolic disease vs. the levels reported after an intervention. We identify the need for further analysis using systems biology approaches and discuss the potential need for treatments to consider their impact on the microbiome.