Metabolic alterations of short-chain fatty acids and TCA cycle intermediates in human plasma from patients with gastric cancer

• Published in: Life sciences (1973) Vol. 309; p. 121010
• Main Authors: Kim, You Lee, Lee, Wonwoong, Chung, So Hyeon, Yu, Byeong Min, Lee, Yong Chan, Hong, Jongki
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 15.11.2022
• Subjects: ammonium; butyrates; decarboxylation; dietary fiber; energy metabolism; fumarates; Gas chromatography; Gastric cancer; gastritis; Human plasma; humans; intestinal microorganisms; intestines; metaplasia; propionic acid; Short-chain fatty acids; stomach neoplasms; succinic acid; Tandem mass spectrometry; TCA cycle intermediates; tricarboxylic acid cycle; Short-chain fatty acids; Gas chromatography; Tandem mass spectrometry; Human plasma; TCA cycle intermediates; Gastric cancer
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2022.121010

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. 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. 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. In conclusion, propionate, cis-aconitate, α-ketoglutarate, and fumarate could be used to assess the progression of gastric cancer. [Display omitted] •Subjects with gastric diseases were assessed by the profile of short-chain fatty acids (SCFAs) and TCA cycle intermediates.•Altered metabolism of SCFAs and TCA cycle intermediates between gastric diseases was revealed.•The metabolites (propionate, butyrate, cis-aconitate, α-ketoglutarate, and fumarate) were supposed as potential biomarkers.•The product/precursor ratios (succinate/propionate, succinate/α-ketoglutarate, and cis-aconitate/citrate) were distorted.