A recent review (JT Chang. NEJM 2020; 383: 2652-2664. Pathophysiology of Inflammatory Bowel Diseases) provides an in-depth description of the pathophysiology of inflammatory bowel disease (IBD). Digesting the article is akin to putting together a 1000 piece puzzle due to the complex interactions.
Some of the Key Points:
- Based on genomewide association studies, there are “more than 240 risk variants that affect intracellular pathways recognizing microbial products (eg. NOD2); the autophagy pathway, which facilitates recycling intracellular organelles and removal of intracellular microorganisms (eg. ATG16L1); genes regulating epithelial barrier function (eg. ECM1); and pathways regulating innate and adaptive immunity (eg. IL23R and IL10).”
- In this article, Figure 1 and 2 describe the intestinal mucosal immune system in health and disease. At baseline, this system promotes an antiinflammatory state “by virtue of active down-regulation of immune responses. For example, unlike macrophages in other parts of the body, intestinal macrophages do not produce inflammatory cytokines” after exposure to bacteria.
- Dysbiosis is present with IBD; however, studies have been “unable to infer causal relationships.”
- Germ-free mice, when given fecal material from patients with IBD have increased susceptibility to colitis as compared to those who received fecal material from a healthy person.
- Thus, this leads to potential for mitigating intestinal inflammation by modulation of the microbiome.
- However, the authors note that humans are colonized by trillions of viral, fungal, bacterial, and eukaryotic microbes.
- Other components of IBD pathophysiology: reduced mucus layer, increased microbial adherence, dysregulation of tight junctions/increased permeability, dysfunctional Paneth cells, TNF, IL23, IL12, IL6, IL 17A, IL17F, IL22, Interferon-gamma, integrins, JAK inhibitors, T-cells
My take: This article is a useful reference detailing the complexity of IBD pathophysiology and tries to summarize a whole textbook of information into 12 pages.
Related blog posts:
- Patterns and Puzzles with VEO-IBD This is a very good review and the image on this day has one of my favorite patient t-shirts.
- How Very Early Onset-Inflammatory Bowel Disease is Different, Plus One
- Underlyling Genetic Disease in Pediatric IBD
- VEO-IBD -Useful Position Paper
- More IBD Cases Than Ever in Young Canadian Children | gutsandgrowth
- Expanding VEO Variants
- Why the Genetics of Inflammatory Bowel Diseases Matter Now