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

Area of Science:

• Immunology
• Microbiology
• Metabolomics

Background:

• Mucosal-associated invariant T cells recognize bacterial antigens via MR1.
• MR1 knockout mice exhibit distinct gut microbiota and resistance to Clostridioides difficile infection.
• Antibiotic treatment significantly alters gut microbiota composition and function.

Purpose of the Study:

• To investigate the impact of cefoperazone treatment on gut microbiota and metabolome in MR1 knockout versus wild-type mice.
• To identify metabolic differences associated with altered microbiota in the absence of MR1.
• To explore metabolic biomarkers complementary to metagenomic data.

Main Methods:

• LC/MS-based untargeted metabolomics applied to fecal, small intestinal, and cecal samples.
• Cefoperazone treatment administered to adult C57Bl/6J wild-type and MR1 knockout mice for five days.
• Multivariate statistical analysis (PLS-DA) and correlation analysis used to interpret metabolomic data.

Main Results:

• Cefoperazone treatment caused less disturbance to the gut microbiota in MR1 knockout mice compared to wild-type mice.
• Significant increases in carbohydrate metabolites were observed in wild-type mice but not in MR1 knockout mice post-treatment.
• Gamma-aminobutyric acid (GABA) and riboflavin levels correlated with observed metabolic changes, serving as potential biomarkers.

Conclusions:

• MR1 plays a role in modulating the gut microbiota's response to antibiotic-induced perturbations.
• Metabolomic profiling provides valuable insights into host-microbe-drug interactions, complementing metagenomics.
• Distinct metabolic profiles in MR1 knockout mice suggest a role in resistance to gut dysbiosis and infection.