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HIRI researchers establish a link between the form and function of intestinal bacterium Bacteroides thetaiotaomicron
Despite being genetically identical, bacteria can vary considerably in shape and size. Whether these variations affect bacterial function has remained an open question. Researchers at the Helmholtz Institute for RNA-based Infection Research (HIRI) and the Chair of Microbiology of the Julius-Maximilians-Universität Würzburg (JMU) have now characterized the functional differences between various forms of the gut bacterium Bacteroides thetaiotaomicron. They demonstrated a link between cell type and metabolic function. These findings offer deeper insights into microbial gut diversity and pave the way for new possibilities in microbiome-based therapies. The study was recently published in the journal Cell Reports.
The human gut is home to a diverse microbial community. These bacteria play a vital role in maintaining our health by supporting digestion and protecting against disease. They exhibit extreme diversity, with differences not only present at the species level. Even bacteria from the same species with the same genetic composition can look different.
A good example of this is the genus Bacteroides, which represents some of the most common intestinal bacteria and exhibits significant morphological variation. This means they come in different shapes and sizes, known as morphotypes. Until now, the molecular mechanisms behind this diversity and its potential effect on bacterial function have been poorly understood. Researchers from the Helmholtz Institute for RNA-based Infection Research (HIRI), a site of the Braunschweig Helmholtz Centre for Infection Research (HZI) in cooperation with the Julius-Maximilians-Universität Würzburg (JMU), and the Chair of Microbiology at JMU have investigated the functional differences between the various morphotypes of Bacteroides thetaiotaomicron.
Form follows function
The analysis revealed that even within a seemingly homogeneous culture of bacteria, there are significant differences in gene activity between distinct cell morphotypes. “Many of these genes are responsible for producing proteins that are involved in metabolism. This indicates that morphological differentiation is due to metabolic specialization,” explains lead author Alexander Westermann, an affiliated scientist at HIRI and professor at JMU.
“Our results were unexpected,” adds Élise Bornet, a doctoral student in Westermann's lab and first author of the study. “They show that bacterial cell size differences are not just due to the cell cycle. Rather, it appears to be a deliberate strategy of commensals to thrive in an environment as dynamic as the human gut.”
A novel method
First, the researchers separated and sorted the bacteria based on their size. To characterize the differences in gene activity, the team developed an ultra-sensitive RNA sequencing method in close collaboration with Emmanuel Saliba’s group at the HIRI. This technology makes it possible to determine and analyze the content of ribonucleic acids (RNAs) in biological samples. In addition, the researchers used a staining method called fluorescence in situ hybridization, which allowed them to visualize transcripts directly in the cell. This enabled the team to identify differentially expressed genes as biomarkers for specific cell shapes. The researchers found that these markers are not merely typical of the cell type; some of them are even causally involved in cell size determination.
One advantage of the new method is that it requires only a small amount of material. In fact, just a few cells are sufficient for analysis. “Our protocol is not only important for our current study, but also represents a valuable tool for the research community,” says Westermann. “In the future, our technique could help researchers identify differences in the gene activity of individual cells—both in Bacteroides and in other microbiota species,” adds Bornet.
The gained insights could open up new possibilities for medicine: Since Bacteroides bacteria perform important functions; a better understanding of their diversity could lay the foundation for novel microbiome-based therapies.
Collaborations:
This study is a collaboration between the research groups led by Alexander Westermann, Lars Barquist, Emmanuel Saliba, and Jörg Vogel at the Helmholtz Institute for RNA-based Infection Research (HIRI), the Julius-Maximilians-Universität Würzburg (JMU), the Braunschweig Helmholtz Centre for Infection Research (HZI), the Leibniz Lung Center in Borstel, Stanford University in the United States of America and the University of Toronto in Canada.
Funding:
The study was supported by the European Research Council, the Center for Microbial Single-cell RNA-seq (MICROSEQ) at the University of Würzburg, which is funded by the German Research Foundation (DFG), and the National Institutes of Health. It was also funded by the DFG Priority Program “Emergent Functions of Bacterial Multicellularity” (SPP 2389), the DFG Research Training Group “3D-Infect” (GRK2157), and the DFG Collaborative Research Center DECIDE (SFB 1583). Elise Bornet was supported by the HIRI graduate program “RNA & Infection”. Kerwyn Casey Huang is a Chan Zuckerberg Biohub Investigator.
This press release and an image are also available on our website: https://www.helmholtz-hzi.de/en/media-center/newsroom/news-detail/a-new-perspect....
Helmholtz Institute for RNA-based Infection Research:
The Helmholtz Institute for RNA-based Infection Research (HIRI) is the first institution of its kind worldwide to combine ribonucleic acid (RNA) research with infection biology. Based on novel findings from its strong basic research program, the institute’s long-term goal is to develop innovative therapeutic approaches to better diagnose and treat human infections.
HIRI is a site of the Braunschweig Helmholtz Centre for Infection Research (HZI) in cooperation with the Julius-Maximilians-Universität Würzburg (JMU) and is located on the Würzburg Medical Campus. More information at http://www.helmholtz-hiri.de.
Helmholtz Centre for Infection Research:
Scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig and its other sites in Germany are engaged in the study of bacterial and viral infections and the body’s defense mechanisms. They have a profound expertise in natural compound research and its exploitation as a valuable source for novel anti-infectives. As member of the Helmholtz Association and the German Center for Infection Research (DZIF) the HZI performs translational research laying the ground for the development of new treatments and vaccines against infectious diseases. http://www.helmholtz-hzi.de/en
Media Contact:
Luisa Härtig
Manager Communications
Helmholtz Institute for RNA-based Infection Research (HIRI)
luisa.haertig@helmholtz-hiri.de
+49 (0)931 31 86688
Bornet E, Prezza G, Cecchino L, Jenniches L, Behrends J, Tawk C, Huang KC, Strowig T, Vogel J, Barquist L, Saliba AE, Westermann AJ: Low-input RNA-seq suggests metabolic specialization underlying morphological heterogeneity in a gut commensal bacterium. Cell Reports (2025), DOI: 10.1016/j.celrep.2025.115844
Electron microscope image of Bacteroides thetaiotaomicron, illustrating the differences in the size ...
Source: Élise Bornet
Copyright: Élise Bornet
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