What pathophysiological mechanism is considered for pulmonary involvement in chronic inflammatory bowel disease and vice versa?
Patients with chronic inflammatory bowel disease (IBD) and pulmonary involvement are rarely seen by pneumologists. On the one hand, this is due to the fact that the lung is not one of the preferred extraintestinal manifestations in Crohn's disease and ulcerative colitis. However, it also seems that the idea of the lungs and intestines having something to do with each other is far from everyone’s minds. All the more so when (source 1) there is only an apparent incidental finding in the intestine, and the lung manifestation precedes the IBD symptoms.
If IBD patients also have pulmonary problems, this is in the majority of cases due to IBD medication. The fact that there is also an increased incidence of respiratory diseases in IBD patients independently of this was first published about four decades ago in a case series. The authors' assumption that chronic intestinal inflammation as a systemic disease can also be associated with pulmonary involvement was subsequently confirmed. Conversely, there was also an increased incidence of IBD in patients with chronic respiratory diseases.
Surprising? Not so much, if you look at the embryological similarities of the mucous membranes in the respiratory tract and in the colon. In both cases, there is a border area between the outside and the inside of the body and there are columnar epithelia and a strongly developed submucosal lymphatic system (mucosa-associated lymphoid tissue, MALT).
This is about important defense functions and immunological tasks and at the same time about a key role in pathophysiological derailment. An intact epithelial barrier prevents the penetration of pathogens and antigens into the heavily perfused submucosa. In both chronic lung diseases and IBD, an epithelial barrier disorder leads to chronic inflammatory remodeling processes. In addition, an inflammatory or immunological misregulation can be observed (sources 2, 3 and 4). In addition to chronicity, intermittent phases of acute worsening are clinically substantial in both disease groups.
What struck us in this context was the term "Lung-Gut Cross Talk" coined by Keely et al. (sources 5 and 6). This postulates that not a single mechanism, but an overlap of several components could be responsible for the increased coincidence of COPD in IBD and vice versa. For example:
Lung-Gut Cross Talk also appears to have a say in fungal processes. For example, intestinal fungal dysbiosis can occur after antibiotic therapy if specific microorganisms that promote natural resistance are eliminated. In certain cases, shifts in the fungal balance seem to favor allergic respiratory diseases (source 7).
These results come from animal experiments: In mice, the administration of fluconazole aggravated the symptoms of house dust mite allergy. In a fungus-free environment, this effect did not occur, while feeding mice with dysbiosis-associated fungi aggravated allergic respiratory diseases, even in animals with otherwise normal microflora. CX3CR1-positive mononuclear phagocytes (MNPs) play a role in this, as they are able to recognize and absorb fungi in the intestine. The researchers found out that the allergy-promoting fungal effect required the activation of MNPs mediated by the tyrosine kinase (SYK), potentially by priming fungus-specific T-helper cells.
Sources:
1. Chew MT et al. A Rare Cause of Pulmonary Nodules. Case Rep Gastroenterol 2016;10(3):633-9.eCollection 2016
2. Bernstein CN et al. The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study. Gastroenterology 2005;129:827-36
3. Black H et al. Thoracic manifestations of inflammatory bowel disease. Chest 2007;131:524-32
4. Lu DG et al. Pulmonary manifestations of Crohn's disease. World J Gastroenterol 2014;20:133-41
5th Keely S, Hansbro PM. Lung-gut cross talk: a potential mechanism for intestinal dysfunction in patients with COPD. Chest 2014;145(2):199-200. doi:10.1378/chest.13-2077
6. Douschan P, Olschewski H. Wenn sich der Darm auf die Lunge schlägt. CliniCum pneumo 2017;2:18-23
7. Scanlon ST. Fungi affect gut-lung cross-talk. Science019;363(6423):138-9. doi:10.1126/science.363.6423.138-e