TY - JOUR
T1 - Constipation-Predominant Irritable Bowel Syndrome Females Have Normal Colonic Barrier and Secretory Function
AU - Peters, Stephanie A.
AU - Edogawa, Shoko
AU - Sundt, Wendy J.
AU - Dyer, Roy B.
AU - Dalenberg, Daniel A.
AU - Mazzone, Amelia
AU - Singh, Ravinder J.
AU - Moses, Natalie
AU - Smyrk, Thomas C.
AU - Weber, Christopher
AU - Linden, David R.
AU - Macnaughton, Wallace K.
AU - Turner, Jerrold R.
AU - Camilleri, Michael
AU - Katzka, David A.
AU - Farrugia, Gianrico
AU - Grover, Madhusudan
N1 - Funding Information:
This project was funded by an investigatorinitiated grant by Takeda Pharmaceuticals to Dr Grover. In addition, Dr Grover is supported by NIH K23 (DK103911) and Pilot and Feasibility Award from Mayo Clinic Center for Cell Signaling in Gastroenterology (NIH P30DK084567).
Publisher Copyright:
© 2017 by the American College of Gastroenterology.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - OBJECTIVES:The objective of this study was to determine whether constipation-predominant irritable bowel syndrome (IBS-C) is associated with changes in intestinal barrier and secretory function.METHODS:A total of 19 IBS-C patients and 18 healthy volunteers (all females) underwent saccharide excretion assay (0.1 g 13 C mannitol and 1 g lactulose), measurements of duodenal and colonic mucosal barrier (transmucosal resistance (TMR), macromolecular and Escherichia coli Bio-Particle translocation), mucosal secretion (basal and acetylcholine (Ach)-evoked short-circuit current (Isc)), in vivo duodenal mucosal impedance, circulating endotoxins, and colonic tight junction gene expression.RESULTS:There were no differences in the in vivo measurements of barrier function between IBS-C patients and healthy controls: cumulative excretion of 13 C mannitol (0-2 h mean (s.e.m.); IBS-C: 12.1 (0.9) mg vs. healthy: 13.2 (0.8) mg) and lactulose (8-24 h; IBS-C: 0.9 (0.5) mg vs. healthy: 0.5 (0.2) mg); duodenal impedance IBS-C: 729 (65) Ω vs. healthy: 706 (43) Ω; plasma mean endotoxin activity level IBS-C: 0.36 (0.03) vs. healthy: 0.35 (0.02); and in colonic mRNA expression of occludin, zonula occludens (ZO) 1-3, and claudins 1-12 and 14-19. The ex vivo findings were consistent, with no group differences: duodenal TMR (IBS-C: 28.2 (1.9) Ω cm 2 vs. healthy: 29.8 (1.9) Ω cm 2) and colonic TMR (IBS-C: 19.1 (1.1) Ω cm 2 vs. healthy: 17.6 (1.7) Ω cm 2); fluorescein isothiocyanate (FITC)-dextran (4 kDa) and E. coli Bio-Particle flux. Colonic basal Isc was similar, but duodenal basal Isc was lower in IBS-C (43.5 (4.5) μA cm -2) vs. healthy (56.9 (4.9) μA cm -2), P=0.05. Ach-evoked Î "Isc was similar.CONCLUSIONS:Females with IBS-C have normal colonic barrier and secretory function. Basal duodenal secretion is decreased in IBS-C.
AB - OBJECTIVES:The objective of this study was to determine whether constipation-predominant irritable bowel syndrome (IBS-C) is associated with changes in intestinal barrier and secretory function.METHODS:A total of 19 IBS-C patients and 18 healthy volunteers (all females) underwent saccharide excretion assay (0.1 g 13 C mannitol and 1 g lactulose), measurements of duodenal and colonic mucosal barrier (transmucosal resistance (TMR), macromolecular and Escherichia coli Bio-Particle translocation), mucosal secretion (basal and acetylcholine (Ach)-evoked short-circuit current (Isc)), in vivo duodenal mucosal impedance, circulating endotoxins, and colonic tight junction gene expression.RESULTS:There were no differences in the in vivo measurements of barrier function between IBS-C patients and healthy controls: cumulative excretion of 13 C mannitol (0-2 h mean (s.e.m.); IBS-C: 12.1 (0.9) mg vs. healthy: 13.2 (0.8) mg) and lactulose (8-24 h; IBS-C: 0.9 (0.5) mg vs. healthy: 0.5 (0.2) mg); duodenal impedance IBS-C: 729 (65) Ω vs. healthy: 706 (43) Ω; plasma mean endotoxin activity level IBS-C: 0.36 (0.03) vs. healthy: 0.35 (0.02); and in colonic mRNA expression of occludin, zonula occludens (ZO) 1-3, and claudins 1-12 and 14-19. The ex vivo findings were consistent, with no group differences: duodenal TMR (IBS-C: 28.2 (1.9) Ω cm 2 vs. healthy: 29.8 (1.9) Ω cm 2) and colonic TMR (IBS-C: 19.1 (1.1) Ω cm 2 vs. healthy: 17.6 (1.7) Ω cm 2); fluorescein isothiocyanate (FITC)-dextran (4 kDa) and E. coli Bio-Particle flux. Colonic basal Isc was similar, but duodenal basal Isc was lower in IBS-C (43.5 (4.5) μA cm -2) vs. healthy (56.9 (4.9) μA cm -2), P=0.05. Ach-evoked Î "Isc was similar.CONCLUSIONS:Females with IBS-C have normal colonic barrier and secretory function. Basal duodenal secretion is decreased in IBS-C.
UR - http://www.scopus.com/inward/record.url?scp=85015743578&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85015743578&partnerID=8YFLogxK
U2 - 10.1038/ajg.2017.48
DO - 10.1038/ajg.2017.48
M3 - Article
C2 - 28323272
AN - SCOPUS:85015743578
VL - 112
SP - 913
EP - 923
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
SN - 0002-9270
IS - 6
ER -