Xia Xiao, Yixuan Zhou, Xinwei Li, Jing Jin, Jerika Durham, Zifan Ye, Yipeng Wang, Bernhard Hennig, Pan Deng
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引用次数: 0
Abstract
Background: 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 13C-inulin (a tracer), we first observed dynamic enrichment of 13C-metabolites in cecum contents in the amino acids and short-chain fatty acid metabolism pathways. 13C 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 13C 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 13C-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. Video Abstract.
期刊介绍：
Microbiome is a journal that focuses on studies of microbiomes in humans, animals, plants, and the environment. It covers both natural and manipulated microbiomes, such as those in agriculture. The journal is interested in research that uses meta-omics approaches or novel bioinformatics tools and emphasizes the community/host interaction and structure-function relationship within the microbiome. Studies that go beyond descriptive omics surveys and include experimental or theoretical approaches will be considered for publication. The journal also encourages research that establishes cause and effect relationships and supports proposed microbiome functions. However, studies of individual microbial isolates/species without exploring their impact on the host or the complex microbiome structures and functions will not be considered for publication. Microbiome is indexed in BIOSIS, Current Contents, DOAJ, Embase, MEDLINE, PubMed, PubMed Central, and Science Citations Index Expanded.
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