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Title: Evidence of increased fecal granins in children with irritable bowel syndrome and correlates with symptoms

Author
item SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC)
item OHMAN, LENA - University Of Gothenburg
item STRIDSBERG, MATS - Uppsala University
item CAIN, KEVIN - University Of Washington
item SIMREN, MAGNUS - University Of Gothenburg
item HEITKEMPER, MARGARET - University Of Washington

Submitted to: Neurogastroenterology & Motility
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/7/2018
Publication Date: 1/1/2019
Citation: Shulman, R.J., Ohman, L., Stridsberg, M., Cain, K., Simren, M., Heitkemper, M. 2019. Evidence of increased fecal granins in children with irritable bowel syndrome and correlates with symptoms. Neurogastroenterology & Motility. 31:e13486. https://doi.org/10.1111/nmo.13486.
DOI: https://doi.org/10.1111/nmo.13486

Interpretive Summary: The cause(s) of functional gastrointestinal disorders such as irritable bowel syndrome are unknown. Recent studies suggest that the function of nerves and the immune system in the gut of some children and adults with irritable bowel syndrome may be abnormal. In this study we measured substances (granins) present in stool that reflect the function of certain nerves and immune cells in the intestine. Compared to healthy children, those with irritable bowel syndrome had increased levels of granins. Importantly, the higher the concentration of granins in stool (in the intestine), the greater was the pain experienced by the child. These results will help us understand what factors (e.g., diet, genetics, bacteria) are responsible for causing the altered nerve and immune function in children (and presumably adults) with irritable bowel syndrome.

Technical Abstract: Granins have been implicated in the pathophysiology of irritable bowel syndrome (IBS) in adults. We sought to determine whether fecal granins are altered in children with IBS and associated with symptoms.Children (7-12 years of age) with IBS and healthy controls (HC) kept daily pain and stool diaries for 2 weeks. Stool samples were analyzed for chromogranins A and B (CgA, CgB) and secretogranins II and III (SgII, SgIII). Children also completed psychological measures to assess anxiety, depression, somatization, and internalizing symptoms.Fecal CgB and SgIII concentrations were higher in all the boys (IBS plus HC, n = 48) than in all the girls (IBS plus HC, n = 75) (P = 0.02 and P = 0.046, respectively). CgA and SgIII were greater in children with IBS (n = 52) vs HC (n = 69) (P = 0.01, P = 0.017, respectively). CgB and SgII did not differ between groups. In children with IBS, the number of pain episodes per week and mean daily pain rating correlated positively with all four granins. The number of stools per day correlated positively with CgB and SgII, and the percent of diarrheal stools (6 or 7 on the Bristol Scale) correlated inversely with all four granins in boys but not in girls. Fecal granins did not correlate with psychological measures.As measured by fecal granins, there is evidence of neuroimmune activation in children with IBS. Granins are related to abdominal pain symptoms, stooling frequency, and stool form in children with IBS. Sex influences the fecal concentration of CgB and SgIII.