High-coverage metabolomics uncovers microbiota-driven biochemical landscape of interorgan transport and gut-brain communication in mice

Yunjia Lai, Chih-Wei Liu, Yifei Yang, Yun-Chung Hsiao, Hongyu Ru and Kun Lu ()
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Yunjia Lai: Gillings School of Global Public Health, CB# 7431, University of North Carolina
Chih-Wei Liu: Gillings School of Global Public Health, CB# 7431, University of North Carolina
Yifei Yang: Gillings School of Global Public Health, CB# 7431, University of North Carolina
Yun-Chung Hsiao: Gillings School of Global Public Health, CB# 7431, University of North Carolina
Hongyu Ru: Gillings School of Global Public Health, CB# 7431, University of North Carolina
Kun Lu: Gillings School of Global Public Health, CB# 7431, University of North Carolina

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract The mammalian gut harbors a complex and dynamic microbial ecosystem: the microbiota. While emerging studies support that microbiota regulates brain function with a few molecular cues suggested, the overall biochemical landscape of the “microbiota-gut-brain axis” remains largely unclear. Here we use high-coverage metabolomics to comparatively profile feces, blood sera, and cerebral cortical brain tissues of germ-free C57BL/6 mice and their age-matched conventionally raised counterparts. Results revealed for all three matrices metabolomic signatures owing to microbiota, yielding hundreds of identified metabolites including 533 altered for feces, 231 for sera, and 58 for brain with numerous significantly enriched pathways involving aromatic amino acids and neurotransmitters. Multicompartmental comparative analyses single out microbiota-derived metabolites potentially implicated in interorgan transport and the gut-brain axis, as exemplified by indoxyl sulfate and trimethylamine-N-oxide. Gender-specific characteristics of these landscapes are discussed. Our findings may be valuable for future research probing microbial influences on host metabolism and gut-brain communication.

Date: 2021
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DOI: 10.1038/s41467-021-26209-8

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