Abstract
ackground Gut microbiome metabolites are important modulators of host health and disease. However, the overall metabolic potential of the gut microbiome and interactions with the host organs have been underexplored. Results Using stable isotope resolved metabolomics (SIRM) in mice orally gavaged with 13 C-inulin (a tracer), we first observed dynamic enrichment of 13 C-metabolites in cecum contents in the amino acids and short-chain fatty acid metabolism pathways. 13 C labeled metabolites were subsequently profiled comparatively in plasma, liver, brain, and skeletal muscle collected at 6, 12, and 24 h after the tracer administration. Organ-specific and time-dependent 13 C metabolite enrichments were observed. Carbons from the gut microbiome were preferably incorporated into choline metabolism and the glutamine-glutamate/GABA cycle in the liver and brain, respectively. A sex difference in 13 C-lactate enrichment was observed in skeletal muscle, which highlights the sex effect on the interplay between gut microbiome and host organs. Choline was identified as an interorgan metabolite derived from the gut microbiome and fed the lipogenesis of phosphatidylcholine and lysophosphatidylcholine in host organs. In vitro and in silico studies revealed the de novo synthesis of choline in the human gut microbiome via the ethanolamine pathway, and Enterococcus faecalis was identified as a major choline synthesis species. These results revealed a previously underappreciated role for gut microorganisms in choline biosynthesis. Conclusions Multicompartmental SIRM analyses provided new insights into the current understanding of dynamic interorgan metabolite transport between the gut microbiome and host at the whole-body level in mice. Moreover, this study singled out microbiota-derived metabolites that are potentially involved in the gut-liver, gut-brain, and gut-skeletal muscle axes.
Document Type
Article
Publication Date
2024
Digital Object Identifier (DOI)
https://doi.org/10.1186/s40168-024-01808-x
Funding Information
This work was supported by the National Natural Science Foundation of China (82373942), Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD), Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases, and the National Institute of Environmental Health Sciences, National Institutes of Health grant P42 ES007380. The content is solely the responsibility of the authors and does not necessarily represent the official views the National Institutes of Health.
Repository Citation
Xiao, Xia; Zhou, Yixuan; Li, Xinwei; Jin, Jing; Durham, Jerika; Ye, Zifan; Wang, Yipeng; Hennig, Bernhard; and Deng, Pan, "13 C-Stable isotope resolved metabolomics uncovers dynamic biochemical landscape of gut microbiome-host organ communications in mice" (2024). Animal and Food Sciences Faculty Publications. 94.
https://uknowledge.uky.edu/animalsci_facpub/94
Notes/Citation Information
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