Da Eun Jang1, Ji Hyun Bae2, Yoo Jin Chang1, Yoon Hoo Lee1, Ki Taek Nam3, Il Yong Kim4, Je Kyung Seong4, Yong Chan Lee5, Su Cheong Yeom6,7. 1. Graduate School of International Agricultural Technology, Seoul National University, 1447 Pyeongchang-Ro, Daewha, Pyeongchang, Gangwon, 25354, Republic of Korea. 2. Designed Animal and Transplantation Research Institute, Institute of Greenbio Research and Technology, Seoul National University, 1447 Pyeongchang-Ro, Daewha, Pyeongchang, Gangwon, 25354, Republic of Korea. 3. Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 25354, Republic of Korea. 4. Department of Veterinary Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea. 5. Yonsei University, 50 Yonsei-ro Seodaemun-gu, Seoul, 03722, Republic of Korea. 6. Graduate School of International Agricultural Technology, Seoul National University, 1447 Pyeongchang-Ro, Daewha, Pyeongchang, Gangwon, 25354, Republic of Korea. scyeom@snu.ac.kr. 7. Designed Animal and Transplantation Research Institute, Institute of Greenbio Research and Technology, Seoul National University, 1447 Pyeongchang-Ro, Daewha, Pyeongchang, Gangwon, 25354, Republic of Korea. scyeom@snu.ac.kr.
Abstract
BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder involving changes in normal bowel movements. The pathophysiology of IBS is not clearly understood owing to the lack of identifiable pathological abnormalities and reliable biomarkers. AIM: The aim of this study was to discover the novel and reliable biomarker for IBS. METHOD: In this study, neonatal maternal separation (NMS) stress model was used for the IBS mouse model. Further assessment was conducted with whole gastrointestinal transit test, quantitative RT-PCR, histological examination, and western blot. RESULTS: Male pups developed symptoms similar to those of human IBS with diarrhea (IBS-D), such as low-grade inflammation, stool irregularity, and increased bowel motility. NMS stress influenced to the interstitial cells of Cajal (ICC) and induced altered bowel motility, resulting in IBS-D-like symptoms. In addition, we found neuronal nitric oxide synthase (nNOS) to be a novel biomarker for ICC under NMS stress. nNOS expression was only observed in the ICC of the submucosal plexus of IBS-D mice, and the inhibition of nNOS changed the phenotype from IBS-D to IBS with constipation. CONCLUSION: Our study demonstrates that early-life stress can influence to ICC and modulate bowel activity and that nNOS might be used as a biomarker for ICC stimulation in IBS.
BACKGROUND:Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder involving changes in normal bowel movements. The pathophysiology of IBS is not clearly understood owing to the lack of identifiable pathological abnormalities and reliable biomarkers. AIM: The aim of this study was to discover the novel and reliable biomarker for IBS. METHOD: In this study, neonatal maternal separation (NMS) stress model was used for the IBSmouse model. Further assessment was conducted with whole gastrointestinal transit test, quantitative RT-PCR, histological examination, and western blot. RESULTS: Male pups developed symptoms similar to those of humanIBS with diarrhea (IBS-D), such as low-grade inflammation, stool irregularity, and increased bowel motility. NMS stress influenced to the interstitial cells of Cajal (ICC) and induced altered bowel motility, resulting in IBS-D-like symptoms. In addition, we found neuronal nitric oxide synthase (nNOS) to be a novel biomarker for ICC under NMS stress. nNOS expression was only observed in the ICC of the submucosal plexus of IBS-D mice, and the inhibition of nNOS changed the phenotype from IBS-D to IBS with constipation. CONCLUSION: Our study demonstrates that early-life stress can influence to ICC and modulate bowel activity and that nNOS might be used as a biomarker for ICC stimulation in IBS.
Authors: Luis Alberto Bravo-Vázquez; Ixchel Medina-Ríos; Luis David Márquez-Gallardo; Josué Reyes-Muñoz; Francisco I Serrano-Cano; Surajit Pathak; Antara Banerjee; Anindya Bandyopadhyay; Asim K Duttaroy; Sujay Paul Journal: Dig Dis Sci Date: 2022-05-04 Impact factor: 3.487