Ulcerative Colitis

UC Pathophysiology

What is ulcerative colitis?

The pathway to inflammation

Ulcerative colitis (UC) is an immune-mediated inflammatory disorder affecting the colon.1–4

The incidence of UC is similar between men and women.1,4 Although onset can occur at any age,1 UC most commonly presents first in early adulthood, and its prevalence is rising substantially worldwide.1,4

The key symptoms of UC are bloody diarrhoea, faecal urgency, tenesmus (cramping rectal pain) and pain in the lower abdomen.5

UC is characterised by relapsing and remitting mucosal inflammation, which usually involves the rectum and extends proximally to a variable extent through the colon.1,4

In UC, inflammation is continuous throughout the affected area of the colon, and is limited to the mucosa and submucosa.1,3

UC can cause fibrosis and structural changes in the colon, which are associated with additional risks, such as surgery and cancer.3

Although UC can be effectively managed with treatment, there is no cure.1,4

Disease localisation

UC disease localisation and subtypes by extent of colon inflammation

Figure reproduced from Yeshi K, Ruscher R, Hunter L, et al. 20204

Under-recognition of the disabling and progressive nature of UC often leads to its suboptimal treatment3

What causes UC?

The pathophysiology of UC is complex, and understanding continues to evolve.1,2 Multiple interdependent factors may drive the disease pathophysiology.1,2,4,6,7

In UC, the activity of pro- and anti-inflammatory mediators is dysregulated, provoking an exaggerated immune response and initiating a chronic cycle of inflammation.6–8

Impairment of the epithelial and mucus layer barrier in the colon due to dysregulation of inflammatory mediators, such as interleukin (IL)-13, is strongly implicated in UC pathogenesis.1,2,4,6,7

Impaired barrier function increases the permeability of the epithelial layer of the intestine.1,2,4,6 This causes aberrant activation of antigen-presenting cells (APCs) in response to otherwise harmless intestinal bacteria (commensal microbiota), which in turn initiates an inappropriate inflammatory response.1,2,4,6,7

Numerous cells and inflammatory processes are implicated in UC pathophysiology4,7

Other factors known to contribute to or increase the risk of developing dysregulated inflammation in UC1,4,7,9

Genetic factors1,4,7,9

  • Family history is a significant risk factor for UC; first-degree relatives of patients with UC have a four-fold higher risk of developing the condition compared with the general population
  • Numerous genetic risk loci have been identified for UC, many of which are related to gut immunity

Microbial influences1,4,9

  • Commensal gut bacteria are essential for intestinal homeostasis and health, and disruption is associated with intestinal inflammation
  • The gut microbiome of patients with UC is dysregulated, with evidence for an absence of certain bacteria that are important for    gut health; however, it is not yet clear what role this plays in UC pathogenesis
  • Numerous environmental and dietary factors can affect the gut microbiome

Environmental and lifestyle factors1,4

  • A range of environmental and lifestyle factors are associated with UC, although their exact roles remain unclear

Figure reproduced from Yeshi K, Ruscher R, Hunter L, et al. 20204

Related 

Burden of UC

Patients with UC face a substantial burden.

Unmet Needs

Many challenges associated with UC management remain to be addressed.


REFERENCES 1. Du L and Ha C. Gastroenterol Clin N Am 2020;49(4):643–654. 2. Ashton JJ, Green Z, Kolimarala V and Beattie MR. Exp Rev Gastroenterol Hepatol 2019;13(11):1049–1063. 3. Le Berre C, Ananthakrishnan AN, Danese S, et al. Clin Gastroenterol Hepatol 2020;18(1):14–23. 4. Yeshi K, Ruscher R, Hunter L, et al. J Clin Med 2020;9(5):1273. 5. Danese S, Allez M, van Bodegraven AA, et al. Dig Dis 2019;37(4):496739. 6. Coskun M, Salem M, Pedersen J and Nielsen OH. Pharmacol Res 2013;76:1–8. 7. Neurath MF. Nat Rev Immunol 2014;14(5):329–342. 8. Fernández-Clotet A, Castro-Poceiro J and Panés J. Curr Pharm Des 2019;25(1):32–40. 9. Hvas CL, Bendix M, Dige A, et al. Immunopharmacol Immunotoxicol 2018;40(6):446–460. 10. Veny M, Fernandez-Clotet A and Panes J. Pharmacol Res 2020;159:105050.