A study reported in Proceedings of the National Academy of Sciences (PNAS) shows how the presence of a specific protein called IL-22BP affects the composition of the gut microbiota and the body's response to a bacterial infection.
We found that mice that do not produce this protein are better protected against intestinal infections caused by bacteria such as Clostridioides difficile And Citrobacter rodentium. ”
Marco Aurélio Ramirez Vinolo, co-author of the article
He is a professor at the Institute of Biology of the State University of Campinas (IB-UNICAMP) in Brazil and head of the Immunoinflammation Laboratory there.
IL-22BP (interleukin-22-binding protein) reduces the available amount of IL-22, a protein produced by cells of the immune system that helps maintain the intestinal barrier, strengthens intestinal mucosal cells and is involved in the production of antimicrobial substances.
“Our explanation for this finding is that interleukin 22 is more effective in the absence of IL-22BP in enhancing intestinal defenses before the onset of infection,” said Vinolo, who received funding from FAPESP to study the molecular mechanisms of the intestinal microbiota during inflammation.
In the PNAS article, the researchers report that the mice lacking IL-22BP had different gut bacteria, and that the mice with normal IL-22BP production were still protected from infection when these bacteria were transferred to them. This suggests that the absence of the binding protein led to a beneficial modulation of the gut microbiota.
“This resistance to infection was associated with increased production of short-chain fatty acids, which are released by the fermentation of dietary fiber by gut bacteria and have beneficial effects on gut health, including promoting an anti-inflammatory environment and strengthening the intestinal barrier,” said José Luís Fachi, lead author of the article and a postdoctoral fellow at Washington University School of Medicine (WUSM) in the United States.
Fachi was invited by FAPESP during his doctoral thesis on the interaction between intestinal bacteria and colonization by C. difficile a bacillus that is resistant to several antimicrobials and often causes hospital-acquired infections. Short-chain fatty acids are produced by bacterial metabolism during the fermentation of dietary fiber and protect the intestine from infections such as those caused by C. difficile.
The absence of IL-22BP alters the composition and functionality of the gut microbiota, resulting in a beneficial profile for the organism, according to Vinolo, Fachi's PhD supervisor. “This highlights the role of the gut microbiota in regulating the organism's responses and indicates the possibility of attenuating or preventing intestinal infections by inhibiting IL-22BP,” he said.
Next Steps
Future studies can now be designed to better understand the discovery and use it to develop treatments. “The critical next step is to investigate the efficacy of IL-22BP inhibitors in animal models and potentially in clinical trials to treat severe intestinal infections,” Fachi said. Another possibility is to study how different types and amounts of fiber affect the production of short-chain fatty acids. “The composition of the gut microbiota in the absence of IL-22BP can provide valuable information,” he added.
Modulation of the intestinal microbiota may have positive effects on other inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, as well as on infections caused by other pathogens.
“Uncovering how IL-22 interacts with other immune system molecules and cells in the absence of IL-22BP will help us better understand its function in intestinal immunity. Future studies may transform our understanding of the role of these proteins in intestinal health and lead to the development of new therapeutic strategies to prevent and treat intestinal infections,” Vinolo said.
Researchers from the Department of Genetics, Evolution, Microbiology and Immunology at IB-UNICAMP and the Department of Pathology and Immunology at WUSM participated in the study.