Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases

Abstract

Pulmonary abnormalities, dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease (IBD) more frequently than previously recognized. Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms, and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy, with failure to isolate bacterial pathogens on repeated sputum culture, and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel. Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD, the detailed mechanisms of pulmonary-intestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities, dysfunction, or hyper-reactivity among IBD patients need further evaluation. Here, we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy.

Keywords: Biao-Li relationship; Gut-lung crosstalk; Inflammatory bowel disease; Pulmonary symptoms; Social manner.

Figure 1

Model for inflammatory process in lung and intestine during inflammatory bowel disease. Clinical or subclinical inflammation in small and large airways and the lung parenchyma accompanies the main inflammation in the bowel during inflammatory bowel disease.

Figure 2

Summary model of plausible mechanisms of lung-intestine communication underlying inflammatory bowel disease-associated pulmonary involvement. The lungs and intestines are a pair of mutually affected organs. The airways may intrinsically accompany inflammation of the bowel. This distal intrinsic inflammatory response may relate to the common features between the lung and intestine. According to Traditional Chinese Medicine, the lung and intestine have internal and external relationships (Biao-Li). This distal intrinsic inflammatory response may relate to the “social manner” of cells and molecules.

Figure 3

Co-localization of surfactant protein-A and CD68 in normal and inflammatory areas. A: Surfactant protein (SP)-A -positive signal was indicated by fluorescence microscopy (green) fluorescence; CD68-positive signal was identified by rhodamine red-X (red) fluorescence; and the cell nucleus was indicated by Hoechst dye (blue). In the normal area, SP-A was located in the surface of the villi, specific epithelium and submucosae, lamina muscularis, mucosae and lymphoid tissues. CD68-positive cells were mainly found in the submucosae, lamina muscularis, mucosae, and lymphoid tissues and in the epithelium; B: In the inflammatory area, CD68-positive cells were dramatically increased in all levels of the bowel wall; especially CD68-positive macrophages in the epithelia of lamina mucosa. The SP-A-positive macrophages were recruited by activated epithelial cells. Double labeled SP-A and CD68 shows that some CD68-positive macrophages expressed SP-A like molecule in the inflammatory bowel disease tissues (original magnification, × 200). Figures reproduced with permission from reference [53].