Professor Pan Deng's Group Publishes Study on Polysaccharide Metabolism Using Stable Isotope Tracing in Microbiome
The gut microbiome is intricately connected to various host organs, with microbial metabolites playing a crucial role in regulating host metabolic homeostasis and influencing the progression of diseases. Polysaccharides, as high-molecular-weight carbohydrates, are known to improve gut microbial ecology and modulate host metabolism, with their metabolites regarded as the active agents responsible for these effects. Therefore, a comprehensive evaluation of the metabolic interactions between the gut microbiome and host organs is essential for understanding the close relationship between the gut microbiome and the host, as well as for identifying the active substances in polysaccharides.
In a collaborative effort between Professor Pan Deng of the College of Pharmaceutical Sciences, Soochow University, and Professor Bernhard Hennig of the University of Kentucky, a stable isotope tracing method was developed to study the dynamic changes of metabolites within complex metabolic networks. This study unveiled the dynamic transport patterns of polysaccharide-derived metabolites from the gut microbiome across various host organs. The findings were published in the journal Microbiome under the title 13C-Stable Isotope Resolved Metabolomics Uncovers Dynamic Biochemical Landscape of Gut Microbiome-Host Organ Communications in Mice (https://doi.org/10.1186/s40168-024-01808-x).
In recent years, Professor Deng's research group has used stable isotope tracing and multi-omics integration techniques to study the effects of polysaccharides on gut microbial ecology and host metabolism (Environ. Health Perspect. 2022; J. Proteome Res. 2021; J. Lipid Res. 2020). The currect study discovered that 13C-labeled metabolites derived from inulin polysaccharides exhibit organ-specific and time-dependent enrichment. In the cecum contents, 13C-labeled metabolites were mainly enriched in amino acid and short-chain fatty acid metabolic pathways. In the liver, gut microbiome-derived 13C was primarily involved in choline metabolism, while in the brain, it was predominantly involved in the glutamine-glutamate/GABA cycle. Notably, 13C enrichment of lactate in skeletal muscle samples showed significant sex differences, suggesting that gender is an important factor influencing gut microbiome-host organ interactions. Moreover, this study is the first to report that the gut microbiome can synthesize choline from inulin polysaccharides, and that fully 13C-labeled choline is involved in the biosynthesis of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) in multiple host organs. Computational modeling and gut microbial incubation studies revealed that Enterococcus faecalis is the primary bacterial strain responsible for metabolizing polysaccharides and synthesizing choline. This research provides new insights into polysaccharide metabolic pathways and the metabolite-mediated interactions between the gut and the liver, brain, and skeletal muscle.
Doctoral student Xia Xiao from the College of Pharmaceutical Sciences at Soochow University is the first author of this study, with Professor Pan Deng serving as the corresponding author. The research was supported by the National Natural Science Foundation of China and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
Reference:
Xiao X, Zhou Y, Li X, Jin J, Durham J, Ye Z, Wang Y, Hennig B*, Deng P*. 13C-Stable isotope resolved metabolomics uncovers dynamic biochemical landscape of gut microbiome-host organ communications in mice, Microbiome, 2024, 12: 90.
https://doi.org/10.1186/s40168-024-01808-x
Corresponding author:
Prof. Pan Deng’s lab focuses on metabolism research, including drug metabolism and pharmacokinetics, microbiome metabolism and function, and environmental pollutant and human metabolism interactions. She has published more than 50 articles, including the first/corresponding authored paper on Environ Health Perspect, Anal. Chim. Acta, J. Med. Chem, and J. Lipid Res.