Integrated Analysis of Gut Microbiome and Lipid Metabolism in Mice Infected with Carbapenem-Resistant Enterobacteriaceae

Abstract

The disturbance in gut microbiota composition and metabolism has been implicated in the process of pathogenic bacteria infection. However, the characteristics of the microbiota and the metabolic interaction of commensals‒host during pathogen invasion remain more than vague. In this study, the potential associations of gut microbes with disturbed lipid metabolism in mice upon carbapenem-resistant Escherichia coli (CRE) infection were explored by the biochemical and multi-omics approaches including metagenomics, metabolomics and lipidomics, and then the key metabolites‒reaction‒enzyme‒gene interaction network was constructed. Results showed that intestinal Erysipelotrichaceae family was strongly associated with the hepatic total cholesterol and HDL-cholesterol, as well as a few sera and fecal metabolites involved in lipid metabolism such as 24, 25-dihydrolanosterol. A high-coverage lipidomic analysis further demonstrated that a total of 529 lipid molecules was significantly enriched and 520 were depleted in the liver of mice infected with CRE. Among them, 35 lipid species showed high correlations (|r| > 0.8 and p < 0.05) with the Erysipelotrichaceae family, including phosphatidylglycerol (42:2), phosphatidylglycerol (42:3), phosphatidylglycerol (38:5), phosphatidylcholine (42:4), ceramide (d17:1/16:0), ceramide (d18:1/16:0) and diacylglycerol (20:2), with correlation coefficients higher than 0.9. In conclusion, the systematic multi-omics study improved the understanding of the complicated connection between the microbiota and the host during pathogen invasion, which thereby is expected to lead to the future discovery and establishment of novel control strategies for CRE infection.