Probing and manipulating the gut microbiome with chemistry and chemical tools

TL;DR

This paper explores how chemical tools can be used to study and manipulate the gut microbiome, focusing on non-microbicidal interventions and small molecule probes.

Contribution

The paper introduces a classification of chemical interventions for the gut microbiome and highlights new chemical tools like molecular decoys and click chemistry probes.

Findings

Chemical interventions can modulate gut microbiome metabolism for personalized therapies.

Small molecule probes and inhibitors offer new ways to study and manipulate gut microbial enzymes.

Non-microbicidal approaches are gaining importance due to rising antibiotic resistance.

Abstract

The human gut microbiome represents an extended “second genome” harbouring about 1015 microbes containing >100 times the number of genes as the host. States of health and disease are largely mediated by host–microbial metabolic interplay, and the microbiome composition also underlies the differential responses to chemotherapeutic agents between people. Chemical information will be the key to tackle this complexity and discover specific gut microbiome metabolism for creating more personalised interventions. Additionally, rising antibiotic resistance and growing awareness of gut microbiome effects are creating a need for non-microbicidal therapeutic interventions. We classify chemical interventions for the gut microbiome into categories like molecular decoys, bacterial conjugation inhibitors, colonisation resistance-stimulating molecules, “prebiotics” to promote the growth of beneficial microbes, and inhibitors of specific gut microbial enzymes. Moreover, small molecule probes, including click chemistry probes, artificial substrates for assaying gut bacterial enzymes and receptor agonists/antagonists, which engage host receptors interacting with the microbiome, are some other promising developments in the expanding chemical toolkit for probing and modulating the gut microbiome. This review explicitly excludes “biologics” such as probiotics, bacteriophages, and CRISPR to concentrate on chemistry and chemical tools like chemoproteomics in the gut-microbiome context.

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