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Anal Chem. 2018 Feb 20;90(4):2475-2483. doi: 10.1021/acs.analchem.7b02859. Epub 2018 Jan 30.

Strategy for an Association Study of the Intestinal Microbiome and Brain Metabolome Across the Lifespan of Rats.

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Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233, China.
University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.
Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University , Shanghai 200240, China.
Biostatistics and Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa , Honolulu, Hawaii 96813, United States.


There is increased appreciation for the diverse roles of the microbiome-gut-brain axis on mammalian growth and health throughout the lifespan. Numerous studies have demonstrated that the gut microbiome and their metabolites are extensively involved in the communication between brain and gut. Association study of brain metabolome and gut microbiome is an active field offering large amounts of information on the interaction of microbiome, brain and gut but data size and complicated hierarchical relationships were found to be major obstacles to the formation of significant, reproducible conclusions. This study addressed a two-level strategy of brain metabolome and gut microbiome association analysis of male Wistar rats in the process of growth, employing several analytical platforms and various bioinformatics methods. Trajectory analysis showed that the age-related brain metabolome and gut microbiome had similarity in overall alteration patterns. Four high taxonomical level correlated pairs of "metabolite type-bacterial phylum", including "lipids-Spirochaetes", "free fatty acids (FFAs)-Firmicutes", "bile acids (BAs)-Firmicutes", and "Neurotransmitters-Bacteroidetes", were screened out based on unit- and multivariant correlation analysis and function analysis. Four groups of specific "metabolite-bacterium" association pairs from within the above high level key pairs were further identified. The key correlation pairs were validated by an independent animal study. This two-level strategy is effective in identifying principal correlations in big data sets obtained from the systematic multiomics study, furthering our understanding on the lifelong connection between brain and gut.

[Indexed for MEDLINE]

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