Supernatants of irritable bowel syndrome mucosal biopsies impair human colonic smooth muscle contractility.
BACKGROUND
Changes in intestinal motility are likely to contribute to irritable bowel syndrome (IBS) pathophysiology. The aim of the study was to investigate the effects of IBS mucosal supernatants on human colonic muscle contractility.


METHODS
Supernatants were obtained from biopsies of 18 IBS patients-nine with constipation (IBS-C) and nine with diarrhea-predominant IBS (IBS-D)-and nine asymptomatic subjects, used as controls. Colonic circular smooth muscle strips or isolated cells (SMC) were exposed to control or IBS supernatants. Spontaneous phasic contractions on strips and morphofunctional parameters on cells were evaluated in basal conditions and in response to acetylcholine (Ach). Incubation with IBS supernatants was also conducted in the presence of antagonists and inhibitors (namely histamine, protease and prostaglandin antagonists, nuclear factor-kappa B inhibitor, catalase, NADPH oxidase inhibitor, and the cAMP- and/or cGMP-cyclase inhibitors).


RESULTS
Exposure to IBS-C and IBS-D supernatants induced a significant reduction in basal tone and Ach-elicited contraction of muscle strips and a significant shortening and impairment of Ach contraction of SMCs. The NADPH oxidase inhibitor prevented the effect of supernatants, while the protease antagonist only IBS-C effect. No effect was observed with the other antagonists and inhibitors. Dilution of IBS-D supernatants partially restored the effects only on SMCs, whereas dilution of IBS-C supernatants significantly reverted the effects on muscle strips and Ach-elicited response on SMC.


CONCLUSIONS
Supernatants from mucosal biopsies of IBS patients reduce colonic contractility. The observed impairment was concentration dependent, likely occurring through intracellular oxidative stress damage, involving different neuromotor mechanisms depending on the IBS subtype.
Gastroenterology Department, University Campus Bio-medico, Rome, Italy.
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MP
Guarino
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
G
G
Barbara
Department of Internal Medicine and Medical Specialties, University Sapienza, Rome, Italy.
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A
Cicenia
Gastroenterology Department, University Campus Bio-medico, Rome, Italy.
A
A
Altomare
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
M R
MR
Barbaro
Gastroenterology Department, University Campus Bio-medico, Rome, Italy.
S
S
Cocca
Department of Internal Medicine and Medical Specialties, University Sapienza, Rome, Italy.
A
A
Scirocco
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
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http://orcid.org/0000-0002-7777-2936
C
Cremon
Gastroenterology Department, University Campus Bio-medico, Rome, Italy.
S
S
Emerenziani
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
V
V
Stanghellini
Gastroenterology Department, University Campus Bio-medico, Rome, Italy.
M
M
Cicala
Department of Internal Medicine and Medical Specialties, University Sapienza, Rome, Italy.
C
C
Severi
D000328:Adult; D000368:Aged; D003106:Colon / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007419:Intestinal Secretions / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000503:physiopathology*; D009924:Organ Culture Techniques; D055815:Young Adult
colonic motility; human smooth muscle; irritable bowel syndrome; mucosal supernatants