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

Author

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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)

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.

Suggested Citation

  • Yunjia Lai & Chih-Wei Liu & Yifei Yang & Yun-Chung Hsiao & Hongyu Ru & Kun Lu, 2021. "High-coverage metabolomics uncovers microbiota-driven biochemical landscape of interorgan transport and gut-brain communication in mice," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26209-8
    DOI: 10.1038/s41467-021-26209-8
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    1. Koichi Kikuchi & Daisuke Saigusa & Yoshitomi Kanemitsu & Yotaro Matsumoto & Paxton Thanai & Naoto Suzuki & Koki Mise & Hiroaki Yamaguchi & Tomohiro Nakamura & Kei Asaji & Chikahisa Mukawa & Hiroki Tsu, 2019. "Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    2. Dylan Dodd & Matthew H. Spitzer & William Van Treuren & Bryan D. Merrill & Andrew J. Hryckowian & Steven K. Higginbottom & Anthony Le & Tina M. Cowan & Garry P. Nolan & Michael A. Fischbach & Justin L, 2017. "A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites," Nature, Nature, vol. 551(7682), pages 648-652, November.
    3. Peter J. Turnbaugh & Ruth E. Ley & Micah Hamady & Claire M. Fraser-Liggett & Rob Knight & Jeffrey I. Gordon, 2007. "The Human Microbiome Project," Nature, Nature, vol. 449(7164), pages 804-810, October.
    4. Peter J. Turnbaugh & Ruth E. Ley & Michael A. Mahowald & Vincent Magrini & Elaine R. Mardis & Jeffrey I. Gordon, 2006. "An obesity-associated gut microbiome with increased capacity for energy harvest," Nature, Nature, vol. 444(7122), pages 1027-1031, December.
    5. Coco Chu & Mitchell H. Murdock & Deqiang Jing & Tae Hyung Won & Hattie Chung & Adam M. Kressel & Tea Tsaava & Meghan E. Addorisio & Gregory G. Putzel & Lei Zhou & Nicholas J. Bessman & Ruirong Yang & , 2019. "The microbiota regulate neuronal function and fear extinction learning," Nature, Nature, vol. 574(7779), pages 543-548, October.
    6. Alessia Visconti & Caroline I. Le Roy & Fabio Rosa & Niccolò Rossi & Tiphaine C. Martin & Robert P. Mohney & Weizhong Li & Emanuele Rinaldis & Jordana T. Bell & J. Craig Venter & Karen E. Nelson & Tim, 2019. "Interplay between the human gut microbiome and host metabolism," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
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