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Breakthrough in Intestinal Inflammation Treatment: Insights from Medical University of Vienna

Recent advancements from a research team at the Medical University of Vienna have yielded promising findings regarding the treatment of intestinal inflammation. Their study highlights the effects of the semi-synthetic bile acid NorUDCA, which has been shown to suppress the formation of pro-inflammatory T helper 17 cells (TH17) in the intestine and simultaneously foster the development of anti-inflammatory regulatory T cells. These discoveries present a potential new therapeutic avenue for individuals suffering from TH17-mediated intestinal disorders. The comprehensive results of this research were featured in the journal Gut.

NorUDCA, or 24-nor-ursodeoxycholic acid, is a chemically altered form of bile acid that has already exhibited encouraging outcomes in treating liver-related conditions, particularly primary sclerosing cholangitis (PSC), and is undergoing further testing in clinical trials. Given that PSC often coexists with chronic inflammatory bowel diseases, a collaborative effort at MedUni Vienna, led by Michael Trauner from the Clinical Division of Gastroenterology and Hepatology and Wilfried Ellmeier from the Institute of Immunology, focused on NorUDCA’s effects on the intestinal immune response. Their findings indicate that NorUDCA not only inhibits pro-inflammatory TH17 cells but also encourages their transformation into regulatory T cells (Tregs).

The research employed various mouse models that simulate intestinal inflammation, including one where specific immune cells (CD4+ T cells) were transferred into immunocompromised mice to study the dynamics of TH17 cells. Another mouse model utilized human immune cells sourced from PSC patients, providing a framework to better understand the implications for human health. Advanced analytical techniques, such as multicolour flow cytometry and RNA sequencing, along with metabolomic analyses via mass spectrometry, were integral in unraveling the underlying mechanisms of NorUDCA’s anti-inflammatory properties. Senior postdoc and lead author of the study, Ci Ashley Zhu, remarked, “Our validation of NorUDCA’s anti-inflammatory effects in both mouse models and a humanized mouse model using cells from PSC patients suggests that its actions may extend to the human intestinal environment as well.” This research has shed light on the signaling pathways of bile acids within the gut-liver axis.

Providing further context, Wilfried Ellmeier noted, “The findings from our study enhance our understanding of how TH17 cells can be regulated and modulated, and they demonstrate the capacity to influence metabolic activities in immune cells through NorUDCA in the treatment of T-cell-mediated inflammatory diseases. This study exemplifies a productive synergy between fundamental immunology and clinical applications within gastroenterology and hepatology at MedUni Vienna.”

Furthermore, Michael Trauner highlighted the significance of these findings, stating, “The substantial immunomodulatory effects of NorUDCA, noted in both liver and intestinal settings, could pave the way for innovative treatments for inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease, while also addressing its role in PSC management. Preliminary data also suggests that these immunomodulatory effects may extend to neuroinflammatory conditions in the brain, suggesting broader implications beyond the gut-liver axis.”

The origins of this research trace back to a collaborative retreat held by the Immunology Research Cluster at the Medical University of Vienna, receiving financial backing from the Austrian Science Fund (FWF).

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