Kovatcheva-Datchary, P. | Search bioRxiv

bioRxiv2026

ASO-mediated mRNA silencing enables functional analysis and selective depletion of the human microbiota Prevotellaceae

The Prevotellaceae family comprises abundant, taxonomically diverse bacteria of the human microbiota that exhibit remarkable intraspecies variability and distinct phenotypes during host-microbe interactions. Yet functional investigations are hampered by the limited genetic tractability of this medically important bacterial family, rendering it understudied. Here, we apply antisense oligomer (ASO) technology to selectively inhibit translation of single or multiple mRNAs across nine Prevotellaceae species. Using ftsZ- and mreB-related phenotypes as morphogenic readouts, we demonstrate that ASOs can function as a tunable system to study essential gene function. Further, we show that ASOs can selectively deplete target species from a synthetic Bacteroidales community. These results establish ASOs as practical tools for functional genomics and community modulation in otherwise genetically intractable anaerobic microbiota members.

microbiology↗

bioRxiv2019

Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals

Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.

systems biology↗