In a fascinating study published in the Proceedings of the National Academy of Sciences (PNAS), researchers have unveiled how the absence of a specific protein, IL-22BP, can positively impact the gut microbiota and bolster the body’s defense against bacterial infections. This breakthrough could pave the way for new treatments targeting severe intestinal infections.
Scientists discovered that mice lacking IL-22BP, or interleukin 22 binding protein, exhibit greater protection against intestinal infections caused by bacteria such as Clostridioides difficile and Citrobacter rodentium. Marco Aurélio Ramirez Vinolo, a professor at the State University of Campinas (IB-UNICAMP) in Brazil, explained that IL-22BP normally reduces the availability of IL-22, a crucial protein produced by immune cells. IL-22 plays a vital role in maintaining the intestinal barrier, strengthening gut lining cells, and promoting the production of antimicrobial substances.
The research team found that in the absence of IL-22BP, IL-22 becomes more effective at fortifying intestinal defenses even before an infection sets in. This enhanced protective effect was observed in mice, whose gut bacteria composition differed significantly without IL-22BP. Remarkably, when these beneficial bacteria were transferred to mice with normal IL-22BP production, the latter also gained protection against infections.
A key factor in this improved resistance to infection is the increased production of short-chain fatty acids. These beneficial compounds are released by gut bacteria during the fermentation of dietary fibers and contribute to an anti-inflammatory environment while reinforcing the intestinal barrier. José Luís Fachi, the study’s lead author and a postdoctoral fellow at Washington University School of Medicine, emphasized the protective role of these fatty acids against infections like those caused by C. difficile.
Vinolo and his team highlighted that the absence of IL-22BP leads to a beneficial shift in the gut microbiota’s composition and functionality, enhancing the organism’s overall health. This discovery underscores the potential of targeting IL-22BP inhibition as a strategy to mitigate or prevent intestinal infections.
Looking ahead, the researchers are keen to delve deeper into this discovery to develop effective treatments. The next steps involve investigating IL-22BP inhibitors’ efficacy in animal models and clinical trials for severe intestinal infections. Additionally, exploring how different types and quantities of dietary fiber affect short-chain fatty acid production will provide further insights.
Modulating the gut microbiota could also benefit other intestinal inflammatory conditions such as Crohn’s disease and ulcerative colitis, as well as infections from various pathogens. Understanding how IL-22 interacts with other molecules and immune cells in the absence of IL-22BP will enhance our knowledge of intestinal immunity and could lead to novel therapeutic strategies.
This study, a collaborative effort between researchers at IB-UNICAMP and Washington University School of Medicine, marks a significant step forward in understanding and potentially harnessing the gut microbiota’s power to combat intestinal infections. As research progresses, it promises to unlock new pathways for preventing and treating a range of gut-related health issues.
Reference: Fachi, J. L., Di Luccia, B., Gilfillan, S., Chang, H.-W., Song, C., Cheng, J., Cella, M., Vinolo, M. A., Gordon, J. I., & Colonna, M. (December 27, 2023). Deficiency of IL-22–binding protein enhances the ability of the gut microbiota to protect against enteric pathogens. Proceedings of the National Academy of Sciences of the United States of America, 121(19). https://doi.org/10.1073/pnas.2321836121