Aims: Short-chain fatty acids (SCFAs) are produced by gut microbiota from dietary fiber. Since absorbed SCFAs could be introduced into the tricarboxylic acid (TCA) cycle in host cells, the relationships between SCFAs and TCA cycle intermediates might influence to energy metabolism in the human body. For this reason, information on profile changes between SCFAs and TCA cycle intermediates could help unveil pathological mechanisms of gastric cancer. Main methods: A gas chromatography-tandem mass spectrometry (GC–MS/MS) method was developed to simultaneously determine SCFAs and TCA cycle intermediates in human plasma from patients with chronic superficial gastritis (CSG), intestinal metaplasia (IM), and gastric cancer. We applied a tetra-alkyl ammonium pairing method to prevent loss of volatile SCFAs and base decarboxylation of TCA cycle intermediates during sample preparation. To assess gastric diseases, metabolic alterations of SCFAs and TCA cycle intermediates in human plasma with gastric disorders were analyzed by their plasma levels. Key findings: Significantly different metabolic alterations based on the plasma levels of SCFAs and TCA cycle intermediates were investigated in cancer metabolic pathways. Not only propionate and butyrate, mainly produced by gut microbiota, were significantly decreased, but also cis-aconitate, α-ketoglutarate, and fumarate were significantly increased in plasma with IM or gastric cancer, compared to CSG. Further, based on ratios of product to precursor, three metabolic pathways (succinate/propionate, succinate/α-ketoglutarate, and cis-aconitate/citrate) were supposed to be distorted between gastric diseases. Significance: In conclusion, propionate, cis-aconitate, α-ketoglutarate, and fumarate could be used to assess the progression of gastric cancer.
|Publication status||Published - 2022 Nov 15|
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF- 2017M3A9F3047858 and 2021R1C1C1005957 ).
© 2022 Elsevier Inc.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)