Discovery of Drug Candidates for Specific Human Disease Based on Natural Products of Gut Microbes
Cheng-Yu Wang1, Qing-Feng Wen2, Qiao-Qiao Wang1
1Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
Abstract:
The beneficial metabolites of the microbiome could be used as a tool for screening drugs that have the potential for the therapy of various human diseases. Narrowing down the range of beneficial metabolite candidates in specific diseases was primarily a key step for further validation in model organisms. Herein, we proposed a reasonable hypothesis that the metabolites existing commonly in multiple beneficial (or negatively associated) bacteria might have a high probability of being effective drug candidates for specific diseases. According to this hypothesis, we screened metabolites associated with seven human diseases. For type I diabetes, 45 out of 88 screened metabolites had been reported as potential drugs in the literature. Meanwhile, 18 of these metabolites were specific to type I diabetes. Additionally, metabolite correlation could reflect disease relationships in some sense. Our results have demonstrated the potential of bioinformatics mining gut microbes' metabolites as drug candidates based on reported numerous microbe-disease associations and the Virtual Metabolic Human database. More subtle methods would be developed to ensure more accurate predictions.
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