Novel Targets for Modulating the Gut Microbiota and Human Health

Researchers at the Helmholtz Institute for RNA-based Infection Research and the Julius-Maximilians-Universität in Würzburg have discovered a protein and a class of small ribonucleic acids (sRNAs) in Bacteroides thetaiotaomicron that control sugar metabolism.

These findings provide insight into how this gut microbe adjusts to different dietary circumstances. The results broaden knowledge of this bacterium's function in the human gut and could lead to the development of novel therapeutic approaches that use the microbiota to support health. The journal Nature Communications published the study.

The gut significantly influences human health. The ability of bacteria to adapt to the ever-changing intestinal environment significantly impacts the microbiota's composition and roles in human health. Thus, a major focus of microbiota research is how intestinal commensals modify their metabolism in response to daily nutrient fluctuations.

Although the microbial ecosystem in the gut differs from person to person, several species are common. The Bacteroides thetaiotaomicron is one of these species. These microorganisms have dozens of distinct multiprotein complexes that are encoded at polysaccharide utilization loci (PULs), which are specific locations in the genome.

At the transcriptional level, PUL complex synthesis is strictly regulated. However, little is known about how PULs are post-transcriptionally regulated to adjust to changes in their environment.

Researchers at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg, part of the Braunschweig Helmholtz Centre for Infection Research (HZI), have taken on this challenge in collaboration with Julius-Maximilians-Universität Würzburg (JMU) and the Chair of Microbiology at JMU.

Through a series of in vitro and in vivo experiments, they have made significant progress in partnership with the University of Toronto in Canada and Vanderbilt University in Nashville, Tennessee (USA).

Our investigations revealed a remarkably complex RNA-based regulatory circuit governing PUL expression in B. thetaiotaomicron. This complements previous work focusing on transcriptional control mechanisms.”

Alexander Westermann, Study Corresponding Author, Department of Microbiology, Biocenter, University of Würzburg

A Complex Network

This network's central component is the RNA-binding protein RbpB: “We found that the absence of RbpB significantly impairs intestinal colonization,” said Ann-Sophie Rüttiger, Study First Author and PhD student in Alexander Westermann's laboratory.

Hundreds of cellular transcripts interact with RbpB, according to the functional analysis. Among these is a family of 14 paralogous non-coding RNA molecules known as the family of paralogous sRNAs, or FopS for short. RbpB and FopS work together to regulate catabolic processes and make sure the microorganisms can adjust to shifting nutrient conditions as best they can.

This study contributed to our understanding of RNA-coordinated metabolic control, which is crucial for the fitness of dominant microbiota species.”

Ann-Sophie Rüttiger, Study First Author, Department of Microbiology, Biocenter, University of Würzburg

Future research will examine RbpB's structure more closely and pinpoint the main RNA binding mechanisms. The team also intends to investigate the functional parallels between RbpB and other RNA-binding proteins to identify key post-transcriptional hubs in other gut microbiota species.

A comprehensive understanding of the roles of bacterial genes and proteins may greatly aid in the creation of novel therapeutic strategies to treat intestinal and infectious diseases and to enhance health by modifying the gut microbiota's bioactivities.

“Our results offer a promising approach to better understand this microbial consortium and to exploit it for new treatment strategies,” concluded Westermann.