Evaluating Cefoperazone-Induced Gut Metabolic Functional Changes in MR1-Deficient Mice

• Published in: Metabolites Vol. 12; no. 5; p. 380
• Main Authors: Sun, Jinchun, Cao, Zhijun, Smith, Ashley D, Carlson, Jr, Paul E, Coryell, Michael, Chen, Huizhong, Beger, Richard D
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.04.2022; MDPI
• Subjects: Amino acids; Antibiotics; Antigens; Bacteria; Bacterial infections; Bile; Biomarkers; Biosynthesis; Carbohydrates; Cecum; Cefoperazone; Correlation analysis; Digestive system; Digestive tract; Drinking water; Fatty acids; Infections; Intestinal microflora; Lymphocytes T; Major histocompatibility complex; metabolic functioning biomarkers; Metabolism; Metabolites; Metabolomics; Metagenomics; microbiome; Microbiota; Mucosa; Oxidative stress; Peptides; Riboflavin; Rodents; Vitamin B; γ-Aminobutyric acid; carbohydrates; metabolomics; microbiome; metabolic functioning biomarkers
• ISSN: 2218-1989; 2218-1989
• DOI: 10.3390/metabo12050380

Mucosal-associated invariant T cells are activated following the recognition of bacterial antigens presented by the major histocompatibility complex class I-related molecule (MR1). Previous metagenomics data showed that MR1 knock-out (KO) mice had distinct microbiota and displayed a resistance to (CDI) colonization vs. wild-type (WT) mice. In the present study, LC/MS-based untargeted metabolomics are applied to evaluate the changes in metabolic activities, in accordance with the changes in gut microbiota caused by cefoperazone (Cef) treatment. Adult C57Bl/6J WT and MR1 KO mice were given sterile drinking water or spiked with 0.5 mg/mL Cef ad libitum for five days. Fecal pellets were collected daily, and both small intestinal and cecal contents were harvested at sacrifice. The PLS-DA score plots of the metabolomic data indicate that the microbiota is relatively less disturbed by Cef treatment in KO mice, which is consistent with the metagenomics data. The most noticeable differences in the metabolome of KO and WT mice were the increases in carbohydrates in the WT mice, but not in the KO mice. Metabolic functional biomarkers were identified through the correlation analysis of gamma-aminobutyric acid (GABA) and riboflavin. These detected metabolic functional biomarkers could provide information complementary to metagenomics data.