Proenkephalin deletion in hematopoietic cells induces intestinal barrier failure resulting in clinical feature similarities with irritable bowel syndrome in mice.
(2023) Communications biology — Vol. 6, n° 1, p. 1168 (2023)
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- Authors
Rey, Lea 
Battut, Louise Bories, Cyrielle Dietrich, Gilles
- Abstract
- Opioid-dependent immune-mediated analgesic effects have been broadly reported upon inflammation. In preclinical mouse models of intestinal inflammatory diseases, the local release of enkephalins (endogenous opioids) by colitogenic T lymphocytes alleviate inflammation-induced pain by down-modulating gut-innervating nociceptor activation in periphery. In this study, we wondered whether this immune cell-derived enkephalin-mediated regulation of the nociceptor activity also operates under steady state conditions. Here, we show that chimeric mice engrafted with enkephalin-deficient bone marrow cells exhibit not only visceral hypersensitivity but also an increase in both epithelial paracellular and transcellular permeability, an alteration of the microbial topography resulting in increased bacteria-epithelium interactions and a higher frequency of IgA-producing plasma cells in Peyer's patches. All these alterations of the intestinal homeostasis are associated with an anxiety-like behavior despite the absence of an overt inflammation as observed in patients with irritable bowel syndrome. Thus, our results show that immune cell-derived enkephalins play a pivotal role in maintaining gut homeostasis and normal behavior in mice. Because a defect in the mucosal opioid system remarkably mimics some major clinical symptoms of the irritable bowel syndrome, its identification might help to stratify subgroups of patients.
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Citations
Mas-Orea, X., Rey, L., Battut, L., Bories, C., Petitfils, C., Abot, A., Gheziel, N., Wemelle, E., Blanpied, C., Motta, J.-P., Knauf, C., Barreau, F., Espinosa, E., Aloulou, M., Cenac, N., Serino, M., Mouledous, L., Fazilleau, N., & Dietrich, G. (2023). Proenkephalin deletion in hematopoietic cells induces intestinal barrier failure resulting in clinical feature similarities with irritable bowel syndrome in mice. Communications biology, 6(1), 1168. https://doi.org/10.1038/s42003-023-05542-2 (Original work published 2023)