Researchers have discovered a protein and a set of small ribonucleic acids (sRNAs) in *Bacteroides thetaiotaomicron*, which play a key role in managing sugar metabolism. These findings enhance our understanding of how this gut bacterium adjusts to different nutritional environments. Additionally, they provide insights into this bacterium’s importance in human gastrointestinal health and could lead to innovative treatments aimed at improving health through microbiota.
The gut microbiome is essential for human health. The variety of bacteria in the microbiota and their roles in maintaining well-being are greatly affected by their ability to adapt to the changing conditions within the intestine. Therefore, understanding how these intestinal bacteria modify their metabolism in response to daily variations in nutrients has become a focal point in microbiota research.
Although the gut’s microbial communities differ among individuals, certain species are commonly found, including *Bacteroides thetaiotaomicron*. These microbes have numerous multiprotein complexes that are specifically coded in their genomes at designated regions known as polysaccharide utilization loci (PULs). PUL complexes enable the bacteria to attach to, decompose, and absorb specific polysaccharides, aiding their successful colonization of the gut. The production of these complexes is regulated tightly at the transcriptional level. Nevertheless, the post-transcriptional regulation of PULs to respond to environmental changes remains largely unstudied. Researchers at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg, part of the Braunschweig Helmholtz Centre for Infection Research (HZI) in collaboration with Julius-Maximilians-Universität Würzburg (JMU), alongside partners from Vanderbilt University in Nashville, Tennessee (USA) and the University of Toronto in Canada, have addressed this gap through various in vitro and in vivo studies.
“Our research uncovered a surprisingly intricate RNA-based regulatory network that controls PUL expression in *B.* *thetaiotaomicron*,” states Alexander Westermann, the corresponding author of the study published in *Nature Communications*. “This adds to earlier studies focused on transcriptional regulation,” he adds.
A complex network
Central to this regulatory network is the RNA-binding protein RbpB. “We discovered that lacking RbpB notably hinders the ability of the bacteria to colonize the intestine,” mentions Ann-Sophie Rüttiger, the lead author of the study and a PhD student in Westermann’s lab.
The functional analysis showed that RbpB interacts with a vast number of cellular transcripts, which include a group of related non-coding RNA molecules (known as the family of paralogous sRNAs, short for FopS) consisting of 14 members. Together, RbpB and FopS manage catabolic activities, allowing the microbes to adapt effectively to varying nutrient scenarios. “This research has enhanced our understanding of how RNA regulates metabolic processes, which is essential for the survival of key microbiota species,” Rüttiger adds.
Future investigations will focus on a detailed analysis of RbpB’s structure and its critical mechanisms for binding RNA. Additionally, the team plans to explore the functional similarities between RbpB and other RNA-binding proteins to identify key post-transcriptional regulators in different gut microbiota species.
Gaining a deeper understanding of bacterial genes and protein functions could greatly help in crafting new treatment strategies to address infectious and intestinal diseases, as well as in enhancing health by manipulating the beneficial activities of gut microbiota. “Our findings provide a valuable pathway to better understand this microbial community and to utilize it for developing new therapeutic methods,” concludes Westermann.
