Association between Gut Microbiome and Metabolome in Mice Suffering from Acute Carbapenem-Resistant <i>Escherichia coli</i> Infection

Increasing evidence highlighted the metabolic associations between host and gut microbiota during infection. However, how host–gut microbiota metabolic partnership response to Carbapenem-resistant Escherichia coli (CRE) infection has yet to be elucidated. In this study, we subjected the mice to a single intraperitoneal injection of CRE, and studied the alterations of the small molecule metabolites derived from host-microbial co-metabolism, as well as the gut microbiome in mice, at 24 h after infection by a two-level strategy. A panel of metabolites including 129 in feces and 74 in serum, were found to alter significantly in CRE group. Meanwhile, the relative abundance of 15 OTUs in Actinomycetes (1 OTU), Bacteroidetes (2 OTU), Proteobacteria (1 OTU) and Firmicutes (11 OTU) were observed to change after infection. Intercorrelation analysis demonstrated that 49 cecal metabolites and 42 serum metabolites were associated with the changes of one microbe in the Actinomycetes phylum, two microbes in the Bacteroidetes phylum, and six microbes in the Firmicutes phylum. The observed changes in gut microbiome and metabolome in response to CRE infection are more sensitive than traditional biochemical indicators such as the serum levels of TNF-α. The study of gut microbiota-host metabolic interactions in the early stage of the infection is expected to provide the novel diagnostic methods and therapeutic strategies for CRE infection, which might bring innovative solutions to resolve current challenge.