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Volume 49 Issue 7
Jul.  2022
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Article Navigation >  Journal of Genetics and Genomics  > 2022  >  49(7): 612-623

Mesenteric lymph system constitutes the second route in gut-liver axis and transports metabolism-modulating gut microbial metabolites

doi: 10.1016/j.jgg.2022.03.012
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    a CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;

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    b University of Chinese Academy of Sciences, Beijing 100049, China;

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    c College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China;

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    d Medical School of Chinese PLA, Beijing 100853, China;

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    e State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;

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    f State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;

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    g State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;

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    h Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China;

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    i Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China

Funds:

This work is supported by the National Natural Science Foundation of China (91857101), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29020000), and the National Key Research and Development Program of China (2018YFC2000500).

  • Received Date: 2022-03-23
  • Accepted Date: 2022-03-23
  • Rev Recd Date: 2022-03-23
  • Publish Date: 2022-04-11
    Abstract
  • The gut–liver axis denotes the intricate connection and interaction between gut microbiome and liver, in which compositional and functional shifts in gut microbiome affect host metabolism. Hepatic portal vein of the blood circulation system has been thought to be the major route for metabolite transportation in the gut–liver axis, but the existence and importance of other routes remain elusive. Here, we perform metabolome comparison in blood circulation and mesenteric lymph systems and identify significantly shifted metabolites in serum and mesentery. Using cellular assays, we find that the majority of decreased metabolites in lymph system under high-fat diet are effective in alleviating metabolic disorders, indicating a high potential of lymph system in regulating liver metabolism. Among those, a representative metabolite, L-carnitine, reduces diet-induced obesity in mice. Metabolic tracing analysis identifies that L-carnitine is independently transported by the mesenteric lymph system, serving as an example that lymph circulation comprises a second route in the gut–liver axis to modulate liver metabolism. Our study provides new insights into metabolite transportation via mesenteric lymph system in the gut–liver axis, offers an extended scope for the investigations in host-gut microbiota metabolic interactions and potentially new targets in the treatment of metabolic disorders.
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