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Title: Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome

item SHULMAN, R - Children'S Nutrition Research Center (CNRC)
item JARRETT, M - University Of Washington
item CAIN, K - University Of Washington
item BROUSSARD, E - University Of Washington Medical School
item HEITKEMPER, M - University Of Washington

Submitted to: American Journal of Gastroenterology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/21/2013
Publication Date: 1/17/2014
Citation: Shulman, R.J., Jarrett, M.E., Cain, K.C., Broussard, E.K., Heitkemper, M.M. 2014. Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome. American Journal of Gastroenterology. 49(11):1467-1476.

Interpretive Summary: Up to 15% of children and adults have irritable bowel syndrome (IBS), a disorder that causes abdominal (belly) pain, changes in stooling pattern, and can be related to certain foods. We know little about what causes IBS. In this study in adults, we tested whether the intestine is not working well to filter out things that might be harmful (leaky). We also tested whether this poor functioning of the intestine could associated with changes in the immune system. We found that in some people with IBS, the gut is leaky and is associated with changes in function of the immune system. We are now testing whether this is true in some children with IBS.

Technical Abstract: Alterations in gastrointestinal (GI) permeability and immune measures are present in some patients with irritable bowel syndrome (IBS) but the relationship to symptoms is poorly defined. In adults with IBS, we compared permeability, unstimulated peripheral blood monocyte (PBMC) interleukin-10 (IL-10) levels, IBS life interference, and GI and psychological distress symptoms. In 88 women and 18 men with IBS, GI permeability was quantitated as percent recovery of urinary sucrose and the lactulose/mannitol (L/M) ratio. IL-10 was measured in supernatants from 72-h incubated, unstimulated PBMCs. Participants completed a 4-week daily diary recording IBS life interference on daily activities and work, IBS symptoms, and psychological distress symptoms. They also completed the Brief Symptom Inventory. The L/M ratio but not percent sucrose recovery was significantly correlated with IBS interference with activities and work and retrospectively measured anxiety and depression. Unstimulated PBMC production of IL-10 correlated significantly with IBS interference with daily work, IBS symptom score, and abdominal pain. We identified a subgroup of IBS subjects with higher IL-10 and/or higher L/M ratio who had substantially higher IBS interference and IBS symptom scores. Our findings suggest a distinct subgroup of IBS patients with alterations in gut barrier function. This subgroup is characterized by increased GI permeability and/or increased PBMC production of IL-10. These physiologic alterations reflect more severe IBS as measured by interference of IBS with daily activities and daily IBS symptoms.