Identification of disease ameliorated metabolite candidates from Gut Microbes and their interacting targets based on...

The gut microbiota plays a crucial role in human health and the progression of diseases. As key mediators of the interactions between gut microbiota and host diseases, metabolite changes have a significant influence on disease development and progression. However, without experimental validation by metabolomics, identifying the level of metabolite changes in specific diseases remains challenging. For this reason, we devised a scoring function to quantitatively estimate metabolite changes across disease phenotypes by integrating changes in the relative abundance of gut microbes owning these metabolites, and hereby developed the online repository to reserve these associations of metabolites and diseases. The consequent GMMAD with v2.0 currently contains 83 diseases and 6966 metabolites. Among them, 85,136 associations are of statistical significance (paired-sample t-test, p-value < 0.05 and FDR < 0.1). Notably, the scoring function showed 84.06% consistency with experimentally validated disease-metabolite associations, outperforming the prior semi-qualitative method (72.5%). Aided by this resource, we identified 130 beneficial metabolites across 27 diseases. Among them, literature supports that 48 could ameliorate the disease status in animals or clinical trials. We listed these 48 promising drug molecules on the website. Furthermore, we constructed a metabolite-gene association network and provided information on the origins of metabolites. All the metabolite-associated information would help researchers reveal the mechanisms of how gut microbes regulate disease progression and guide drug development. The GMMAD v2.0 is freely accessible at http://gepa.org.cn/GMMAD2/.