2025-05-20
Intestine–pancreas: a confirmed connection
Gastroenterology and Hepatology
#IBD #Pancreatitis #UlcerativeColitis
#CrohnsDisease
Chronic inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn’s disease (CD), are autoimmune conditions marked by persistent intestinal inflammation with often unpredictable progression. Beyond digestive symptoms, they are known for their systemic nature, frequently causing extraintestinal manifestations that affect the skin, joints, eyes, and liver.
Among these systemic complications, pancreatic involvement remains relatively unexplored. Some clinical studies have reported an increased incidence of pancreatitis — either acute (AP) or chronic (CP) — in patients with IBD. However, this association is still poorly defined due to numerous confounding factors, such as the use of thiopurines, corticosteroids, or the presence of metabolic comorbidities (alcohol use, smoking, dyslipidemia). It remains unclear whether this link reflects a true inflammatory comorbidity or is merely a side effect of treatment.
To clarify this potential connection, the present study was initiated to assess whether there is a causal relationship independent of environmental factors. The objective was to determine whether IBD — UC and CD — genetically increases the risk of pancreatitis, and whether the reverse association is also valid.
In this study, more than 31,000 patients with IBD (13,768 with ulcerative colitis and 17,897 with Crohn’s disease) were selected and compared to over 850,000 control individuals regarding pancreatitis risk.
The findings demonstrate that IBD significantly increases the risk of both acute and chronic pancreatitis. Moreover, ulcerative colitis is associated with a higher risk of both AP and CP, with overrepresentation observed in two independent data sets. In contrast, Crohn’s disease is linked only to an increased risk of AP, with no significant impact on CP. Notably, reverse analysis suggests that acute pancreatitis may exert a protective effect against the development of IBD, particularly Crohn’s disease. This speculative result paves the way for new pathophysiological hypotheses regarding bidirectional interactions between the pancreatic and intestinal axes.
These findings were supported by sensitivity analyses, including tests for horizontal pleiotropy, leave-one-out analyses, and MR-Egger regression, which revealed neither major bias nor significant heterogeneity.
Inflammatory bowel diseases are autoimmune intestinal disorders with systemic implications. Among their potential extra-digestive complications, pancreatic involvement remains poorly characterized both epidemiologically and pathophysiologically. One of the major challenges is to determine whether pancreatitis, whether acute or chronic, constitutes an intrinsic comorbidity of IBD or merely reflects treatment side effects or other confounding factors. The complexity of this link — often clouded by exposure to immunosuppressants, genetic variation, and comorbidities — complicates the interpretation of observational data.
This study aimed to clarify the nature of the relationship between IBD and pancreatitis by eliminating common biases through a bidirectional Mendelian randomization analysis. The results provide, for the first time, robust genetic evidence of a causal relationship between IBD and pancreatitis, particularly in its acute form. They confirm that UC is associated with an increased risk of both acute and chronic pancreatitis, while CD appears to be linked only to acute pancreatitis.
Further research is needed to better understand shared inflammatory mechanisms, especially IL-1 and IL-33 cytokine pathways, and to assess the impact of immunosuppressive treatments on pancreatic risk. These findings could lead to the integration of pancreatic screening into the clinical follow-up of IBD patients, particularly those with UC, to better prevent extra-colonic digestive complications.
Chronic inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn’s disease (CD), are autoimmune conditions marked by persistent intestinal inflammation with often unpredictable progression. Beyond digestive symptoms, they are known for their systemic nature, frequently causing extraintestinal manifestations that affect the skin, joints, eyes, and liver.
Among these systemic complications, pancreatic involvement remains relatively unexplored. Some clinical studies have reported an increased incidence of pancreatitis — either acute (AP) or chronic (CP) — in patients with IBD. However, this association is still poorly defined due to numerous confounding factors, such as the use of thiopurines, corticosteroids, or the presence of metabolic comorbidities (alcohol use, smoking, dyslipidemia). It remains unclear whether this link reflects a true inflammatory comorbidity or is merely a side effect of treatment.
To clarify this potential connection, the present study was initiated to assess whether there is a causal relationship independent of environmental factors. The objective was to determine whether IBD — UC and CD — genetically increases the risk of pancreatitis, and whether the reverse association is also valid.
IBD: a hidden factor in pancreatitis?
In this study, more than 31,000 patients with IBD (13,768 with ulcerative colitis and 17,897 with Crohn’s disease) were selected and compared to over 850,000 control individuals regarding pancreatitis risk.
The findings demonstrate that IBD significantly increases the risk of both acute and chronic pancreatitis. Moreover, ulcerative colitis is associated with a higher risk of both AP and CP, with overrepresentation observed in two independent data sets. In contrast, Crohn’s disease is linked only to an increased risk of AP, with no significant impact on CP. Notably, reverse analysis suggests that acute pancreatitis may exert a protective effect against the development of IBD, particularly Crohn’s disease. This speculative result paves the way for new pathophysiological hypotheses regarding bidirectional interactions between the pancreatic and intestinal axes.
These findings were supported by sensitivity analyses, including tests for horizontal pleiotropy, leave-one-out analyses, and MR-Egger regression, which revealed neither major bias nor significant heterogeneity.
Read next: Should surgery be broader?
An inflammatory link to monitor
Inflammatory bowel diseases are autoimmune intestinal disorders with systemic implications. Among their potential extra-digestive complications, pancreatic involvement remains poorly characterized both epidemiologically and pathophysiologically. One of the major challenges is to determine whether pancreatitis, whether acute or chronic, constitutes an intrinsic comorbidity of IBD or merely reflects treatment side effects or other confounding factors. The complexity of this link — often clouded by exposure to immunosuppressants, genetic variation, and comorbidities — complicates the interpretation of observational data.
This study aimed to clarify the nature of the relationship between IBD and pancreatitis by eliminating common biases through a bidirectional Mendelian randomization analysis. The results provide, for the first time, robust genetic evidence of a causal relationship between IBD and pancreatitis, particularly in its acute form. They confirm that UC is associated with an increased risk of both acute and chronic pancreatitis, while CD appears to be linked only to acute pancreatitis.
Further research is needed to better understand shared inflammatory mechanisms, especially IL-1 and IL-33 cytokine pathways, and to assess the impact of immunosuppressive treatments on pancreatic risk. These findings could lead to the integration of pancreatic screening into the clinical follow-up of IBD patients, particularly those with UC, to better prevent extra-colonic digestive complications.
Read next: IBD: a double burden
Last press reviews
Crohn’s Disease: targeting map for better treatment?
#CrohnsDisease #CD #MAP #vaccine #vaccination <br><br>
Targeting IL-23 – a winning bet?
#UlcerativeColitis #Mirikizumab #UC #IL23 #Immunotherapy #Gastroenterol...