Falk Foundation Symposium 241 Sets New Course for IBD Classification
Inflammatory Bowel Disease: Rethinking Classification, Immunology, and Management
International experts in inflammatory bowel disease (IBD) gathered in Oxford, UK, for the 241st Falk Foundation e.V. Symposium, “Mucosal Immunology Days.” The meeting aimed to review the current state of basic research and to explore immunological aspects of IBD in greater depth. The 31 presentations provided valuable input for a future revision of the Montreal classification of IBD, originally published in 2006.1 The new classification is intended to better reflect the underlying biology of IBD, be practical for clinical use, and ultimately improve outcomes for patients.
The current Montreal classification of IBD considers three key factors in Crohn’s disease: age at diagnosis, disease location, and disease behavior (e.g. stricturing or penetrating disease). In ulcerative colitis, the extent of colonic involvement and the severity of inflammation are central criteria. However, recent findings have raised additional questions that should be addressed in future classification systems. As Prof. Britta Siegmund (Berlin, Germany) emphasized, important unresolved issues include: Why is Crohn’s disease a pan-enteric disease while ulcerative colitis is confined to the colon? Why does ulcerative colitis typically begin in the rectum? Why is there a sharp demarcation in disease extent in ulcerative colitis? These and other questions were the focus of discussions among researchers at the symposium.
Emerging Insights into the Microbiome and Immune Regulation in IBD
Prof. Fiona Powrie (Oxford, UK) highlighted the current challenges in IBD. The incidence of Crohn’s disease and ulcerative colitis is rising globally, with both conditions displaying considerable heterogeneity. In addition, current therapies are not effective for all patients, underscoring the need to better understand the complex biological mechanisms involved. Looking ahead to 2030, Powrie referenced recent research, particularly regarding the gut microbiome. Recent studies have shown that the gut is home not only to protective microorganisms, but also to pathobionts such as Enterocloster clostridioformis, which plays a role in the induction and maintenance of Helicobacter hepaticus-induced colitis.
Interbacterial interactions appear to be crucial in the development of inflammation. Furthermore, recent findings indicate that the responses of T and B cells to microbes differ significantly in IBD patients compared to healthy individuals. Notably, IL-10-positive regulatory T cells (Tregs) interact closely with CD206-positive macrophages. According to Powrie, these discoveries could have important implications for future Treg cell-mediated therapies.
Immune System Variability and Ageing
To better understand the role of the immune system in IBD, Prof. Eoin McKinney (Cambridge, UK) presented his findings on immune system ageing. Notably, immunological age does not necessarily correspond to chronological age. From approximately 60–65 years onward, the immune system undergoes dramatic changes, with a marked increase in variability, described as a “steep decline.” Studying a Sardinian population known for its exceptional longevity, McKinney found that, from age 65, the peripheral B cell repertoire changes rapidly and the naïve B cell compartment undergoes a significant decline.3 Subsequently, B cell-driven immune responses originate from a different source population. The underlying causes of these changes remain speculative.
Sharp Demarcation of Disease Extent in Ulcerative Colitis
The causes of the distinct boundaries of inflammation observed in the colon of patients with ulcerative colitis remain a subject of speculation. Prof. Derek Jewell (Oxford, UK) shared his insights on this phenomenon, highlighting variations in mucin layer thickness across different sections of the colon and the potential toxic effects of butyrate. Compared to the ileum and proximal colon, the mucin layer is significantly thinner in the distal colon, particularly in the rectum. Additionally, the mucin in the distal colon predominantly contains sialo-oligosaccharides.4-6 Butyrate can stimulate mucin production at low concentrations (up to 1 mM); however, at higher concentrations (5–10 mM), it can become toxic to the intestinal epithelium and promote colitis.7
Diet-Induced Immune Responses and the Predictive Value of GPX4
Prof. Timon Adolph (Innsbruck, Austria) reported on the negative effects of the Western diet – particularly in Crohn’s disease – which is characterized by high levels of fat, sugar, and processed foods.8-9 In contrast, the Mediterranean diet has been shown to have protective effects.10 For example, a high-fat diet can induce a type I interferon response in the small intestine.11 Adolph also focused on glutathione peroxidase 4 (GPX4), an enzyme whose expression may be downregulated in Crohn’s disease and could serve as an indicator of disease recurrence following surgery.12 GPX4 protects phospholipids in the membranes of enterocytes from oxidation. Therefore, assessing GPX4 deficiency in the intestinal epithelium could, in the future, help determine whether individuals with Crohn’s disease require dietary restrictions, particularly with respect to unsaturated fatty acids.
Extraintestinal Manifestations in IBD
Dr. Hannah Gordon (Oxford, UK) provided an overview of extraintestinal manifestations (EIMs) in IBD. She noted that EIMs in Crohn’s disease usually occur when inflammation is localized in the colon, whereas in ulcerative colitis, EIMs tend to arise when proximal segments of the colon are involved. Women are more frequently affected than men. Gordon also highlighted that behavioral and neurodevelopmental disorders, such as depression and anxiety, are more common in IBD than are rheumatologic manifestations.13 In her view, IBD should be considered a multisystem disease.
Focus on Joint Involvement
According to immunologist Prof. Christopher Buckley (Oxford, UK), the gut, joints, skin, and eyes are closely interconnected. He raised the question of why inflammation develops in different parts of the body, such as the wrists or the intestines. He hypothesized that distinct cell types at the sites of inflammation may be responsible. Whether this research will influence the development of a new IBD classification remains to be seen.
Source
241st Symposium “Mucosal Immunology Days”, 10.–12.07.2025, Oxford, United Kingdom
References
1 Satsangi J, et al. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55(6):749–753. doi: 10.1136/gut.2005.082909
2 Gu Y, et al. Immune microniches shape intestinal Treg function. Nature. 2024;628:854–862. doi: 10.1038/s41586-024-07251-0
3 Alpert A, et al. A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring. Nature. 2019;25:487–495. doi: 10.1038/s41591-019-0381-y
4 Podolsky DK, Isselbacher KJ. Glycoprotein composition of colonic mucosa. Specific alterations in ulcerative colitis. Gastroenterology. 1984;87(5):991–998
5 Rhodes JM. Unifying hypothesis for inflammatory bowel disease and associated colon cancer: sticking the pieces together with sugar. Lancet. 1996;347(8993):40–44. doi: 10.1016/s0140-6736(96)91563-9
6 Smithson JE, et al. Altered expression of mucins throughout the colon in ulcerative colitis. Gut. 1995;40(2):234–240. doi: 10.1136/gut.40.2.234
7 Finnie IA, et al. Colonic mucin synthesis is increased by sodium butyrate. Gut. 1995;36(1):93–99. doi: 10.1136/gut.36.1.93
8 Adolph T, Tilg, H. Western diets and chronic diseases. Nat Med. 2024;30(8):2133–2147. doi: 10.1038/s41591-024-03165-6
9 Narula N, et al. Food processing and risk of inflammatory bowel disease: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2023;21(10):2483–2495. doi: 10.1016/j.cgh.2023.01.012
10 Godny L, et al. Mechanistic implications of the Mediterranean diet in patients with newly diagnosed Crohn's disease: multiomic results from a prospective cohort. Gastroenterology. 2025;168(5):952–964. doi: 10.1053/j.gastro.2024.12.031
11 Adolph TE, et al. The metabolic nature of inflammatory bowel diseases. Nat Rev Gastroenterol Hepatol. 2022;19(12):753–767. doi: 10.1038/s41575-022-00658-y
12 Verstockt S, et al. Unpublished data
13 Baumgart DC, et al. Network analysis of extraintestinal manifestations and associated autoimmune disorders in Crohn’s disease and ulcerative colitis. NPJ Digit Med. 2025;8:209. doi: 10.1038/s41746-025-01504-6
About Falk Foundation e.V.
The Falk Foundation promotes the exchange and transfer of medical knowledge without direct product reference in gastroenterology and hepatology. With a wide range of continuous education events, publications and media for medical experts, students and researchers in the field of gastroenterology and hepatology, the association based in Freiburg offers current and comprehensive information on disease patterns, diagnostics, and therapy. The Falk Foundation was founded in 1978 by Dr. Dr. Herbert Falk to provide experts in gastroenterology and hepatology with a platform for knowledge exchange. Since then, over 235 international symposia have taken place, around 100 of them in Germany. Additionally, the Falk Foundation promotes and awards several scientific prizes, including the Herbert Falk Prize, which is awarded during an annual symposium. The work of the association is actively shaped by a committee of 13 independent members.
More information: www.falkfoundation.org
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