IDDF2023-ABS-0180 Global metabolomic profiles of 384 gut bacterial strains revealed unique features of different taxa and distinct relationships between phylogeny and metabolites

Background

Gut microbes modulate host phenotypes and are closely related to multiple diseases in humans, ranging from obesity to cancers. Production of active metabolites is a key route through which gut microorganisms influence host physiology. However, limited information about the metabolomics of individual gut bacterial strains greatly hindered the mechanical connections between the gut microbiome and host phenotypes.

Methods

In this study, we analyzed the metabolic profiles of 384 gut microbial strains using untargeted UPLC-MS/MS-based metabolomics. These bacterial strains belonged to 7 phyla, 42 families, 58 genera and 166 species. Their genome drafts were also obtained to perform comparative genomics.

Results

We identified 449 and 165 metabolites in positive and negative ion mode, respectively. Amino acids, fatty acids, nucleotides and their derives, phospholipids, glycolysis products, and oligopeptides are the main products of the gut bacteria. Two groups of metabolites were obviously aggregated and mutually exclusive among different strains. The first group was mainly composed of prostaglandin analogues and lysophosphatidylethanolamines comprising saturated fatty acids, while the other group contained tetrapeptides and unsaturated fatty acids. We found a kind of lysophosphatidylethanolamines comprising monounsaturated fatty acids is a unique metabolite of Proteobacteria. The 3-hydroxydecanoyl ACP dehydrogenase/isomerase (FabA), an essential enzyme for de novo unsaturated fatty acids synthesis, is the key gene that responds to the unique lysophosphatidylethanolamine profile of Proteobacteria bacteria. Using the metabolomic data, we also found there were obvious deviations in the relationships between phylogeny and metabolism.

Conclusions

Collectively, our results revealed global metabolic profiles of 166 gut bacterial species which exhibited distinct relationships between phylogeny and metabolites, providing a useful resource to define mechanistic connections between individual gut bacterial strains and host phenotypes.