Year: 2026
Type: preprint
Abstract: Microbiome studies typically infer function from gene content or expression, but these measurements do not establish which enzymes are catalytically active or what substrates they recognise. Here we use a multiplexed panel of mechanism-based glycosidase probes to map active glycan-processing enzymes directly from caecal samples of mice colonised with a defined, 14-member, human gut microbiota. Activity-based protein profiling identifies host and microbial enzymes involved in starch, β-glucan, xyloglucan and xylan degradation and links them to defined taxa and loci. Decorated probes resolve branch and substitution preferences within active enzyme families, revealing xylanase activities poorly detected by bulk substrate assays. Several prominent activities are assigned to low-abundance Bacteroides species, while enzyme deployment differs among animals sharing a common inoculum and diet. These results establish activity-based chemoproteomics as a complementary layer to metagenomics, transcriptomics and proteomics for defining functional glycan-processing states in host-associated microbiomes.
Source: ChemRxiv
Institutions: University of York, University of Michigan, Leiden University
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7211999725