Segmental regulation of intestinal motility by colitis and the adaptive immune system in the ileum and colon

Gastrointestinal motility disturbances are common in inflammatory bowel disease (IBD); however, their exact causes remain elusive. This study explores the motility of various intestinal segments in both healthy and IBD states, focusing on the role of the adaptive immune system. Using a dextran sulfate sodium (DSS)-induced colitis model in mice lacking B and T lymphocytes, we evaluated motility in the ileum and colon using an organ bath system. In healthy mice, absence of adaptive lymphocytes in the ileum reduces muscarinic receptor sensitivity or increase cholinesterase activity. Colitis increases motility, intensifying the intensity and frequency of spontaneous contractions while decreasing responsiveness to cholinergic stimuli. In the proximal colon, healthy mice lacking adaptive immune system exhibit increased contractile capacity and frequency, along with reduced muscarinic receptor sensitivity or increased cholinesterase activity. Conversely, colitis diminishes contractile capacity regardless of genotype, while recovery increases frequency of spontaneous contractions. In the mid-colon during colitis, healthy mice lacking adaptive immune system exhibit reduced muscarinic receptor sensitivity or increased cholinesterase activity, while the absence of adaptive lymphocytes during colitis exacerbates both spontaneous and stimuli-induced contractions. Finally, in the distal colon, the adaptive immune system enhances stimuli-induced contractility in health and reduces contractility and enhances muscarinic responses during colitis. Overall, intestinal motility in both the ileum and colon is finely regulated, with the adaptive immune system playing a crucial role. These findings contribute to our understanding of IBD pathology, emphasizing the importance of investigating gastrointestinal motility in IBD research. ### Competing Interest Statement The authors have declared no competing interest. * Ach : Acetylcholine AUC : Area under the curve CD : Crohn’s Disease DCs : Dendritic cells DSS : Dextran sulfate sodium ENS : Enteric nervous system IBD : Inflammatory bowel disease IBS : Irritable bowel syndrome ICCs : Interstitial cells of Cajal IL : Interleukin KATP : Adenosine triphosphate (ATP)-sensitive K+ channel NF-Κb : Nuclear factor κB PD2 : -logEC50 PGE2 : Prostaglandin E2 SMCs : Smooth muscle cells SPF : Specific pathogen-free TNF-α : tumor necrosis factor-α Th : T helper cell Tregs : Regulatory T cells UC : Ulcerative Colitis WT : Wild-type