Multi-omics analysis of a synthetic gut microbial community.. Mock multi-omics analysis.

Multi-omics analyses are becoming a method of choice to obtain a holistic view on a biological system. Although they are increasingly employed in microbiome studies, it is not always clear to what extent each ‘omics data type can contribute to our understanding of the dynamic interactions within a microbial community. Here we evaluate the knowledge gained from time-series measurements across five ‘omics layers (16S rRNA gene sequencing, metagenomics, metatranscriptomics, metaproteomics, and metabolomics) in a synthetic community of 32 human gut bacteria upon perturbation by three non-antibiotic drugs. We demonstrate that the ‘omics techniques are highly consistent in estimating relative species abundances across conditions, and highlight the differences in their ability to capture functional changes in response to the drug perturbations. For example, analysis of four ‘omics data types indicated that the antipsychotic drug chlorpromazine selectively inhibits Bacteroidota representatives in the community. Metatranscriptomics analysis further suggested that the drug induces heat shock stress responses in bacteria, while metabolomics revealed concurrent decrease in polysaccharide uptake, likely caused by Bacteroidota depletion. Taken together, our study gives insights into how multi-omics datasets can be used to reveal complex responses to external perturbations in microbial communities.