Constipation-Predominant Irritable Bowel Syndrome Females Have Normal Colonic Barrier and Secretory Function.
OBJECTIVE
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 g13C 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 of13C 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 cm2vs. healthy: 29.8 (1.9) Ω cm2) and colonic TMR (IBS-C: 19.1 (1.1) Ω cm2vs. healthy: 17.6 (1.7) Ω cm2); 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 ΔIsc was similar.


CONCLUSIONS
Females with IBS-C have normal colonic barrier and secretory function. Basal duodenal secretion is decreased in IBS-C.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Stephanie A
SA
Peters
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Shoko
S
Edogawa
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Wendy J
WJ
Sundt
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Roy B
RB
Dyer
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Daniel A
DA
Dalenberg
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA.
Amelia
A
Mazzone
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Ravinder J
RJ
Singh
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Natalie
N
Moses
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Thomas C
TC
Smyrk
Department of Pathology, University of Chicago, Chicago, Illinois, USA.
Christopher
C
Weber
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA.
David R
DR
Linden
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
Wallace K
WK
MacNaughton
Departments of Pathology and Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Jerrold R
JR
Turner
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Michael
M
Camilleri
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
David A
DA
Katzka
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Gianrico
G
Farrugia
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Madhusudan
M
Grover
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D016022:Case-Control Studies; D018679:Cholinergic Agonists / Q000494:pharmacology; D057167:Claudins / Q000235:genetics; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D003248:Constipation / Q000209:etiology; D004386:Duodenum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D017097:Electric Impedance; D004731:Endotoxins / Q000097:blood; D005260:Female; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D007792:Lactulose / Q000378:metabolism*; D008353:Mannitol / Q000378:metabolism*; D008875:Middle Aged; D062793:Occludin / Q000235:genetics; D010539:Permeability; D012333:RNA, Messenger / Q000378:metabolism*; D019108:Tight Junctions / Q000235:genetics; D062825:Zonula Occludens Proteins / Q000235:genetics
D018679:Cholinergic Agonists; D057167:Claudins; D004731:Endotoxins; D062793:Occludin; D012333:RNA, Messenger; D062825:Zonula Occludens Proteins; D008353:Mannitol; D007792:Lactulose; D000109:Acetylcholine