Rome III Functional Constipation and Irritable Bowel Syndrome With Constipation Are Similar Disorders Within a Spectrum of Sensitization, Regulated by Serotonin

Background & AimsPatients with irritable bowel syndrome with constipation (IBS-C) and patients with functional constipation (FC) have similar symptoms, and these disorders overlap in their diagnostic features. Little is known about their overlap in physiology or the involvement of serotonin signaling. We investigated relationships between platelet-depleted plasma concentrations of serotonin, gastrointestinal symptoms, and motor−sensory function in patients with FC or IBS-C compared with healthy volunteers (controls).MethodsWe measured platelet-depleted plasma concentrations of serotonin in fasting and fed individuals with IBS-C (n = 23; 19−50 years old), FC (n = 11; 25−46 years old), and controls (n = 23; 20−49 years old) recruited in Manchester, UK. We also quantified abdominal and bowel-related symptoms, rectal sensitivity, oro-cecal transit, and colonic (whole intestine) transit.ResultsPatients with IBS-C or FC had similar baseline symptoms, bowel habits, oro-cecal and colonic transit, and fasting concentrations of serotonin and response to meal ingestion. Only patients with IBS-C had increased symptoms after ingestion of a meal (P < .001)—these patients tended to have lower sensory thresholds than patients with FC. Defecation frequency in the combined group of patients with IBS-C or FC correlated inversely with serotonin concentration (r = −0.4; P = .03). Serotonin concentration also correlated with pain threshold (r = 0.4; P = .02) and stool threshold (r = 0.5; P = .06), which correlated inversely with defecation frequency (r = −0.3; P = .10).ConclusionsFC and IBS-C, based on Rome III criteria, are not distinct disorders, symptomatically or physiologically. Instead, they appear to lie in a spectrum of visceral sensitivity modulated by serotonin signaling. Symptom response to meal ingestion should be considered in patient classification. Patients with irritable bowel syndrome with constipation (IBS-C) and patients with functional constipation (FC) have similar symptoms, and these disorders overlap in their diagnostic features. Little is known about their overlap in physiology or the involvement of serotonin signaling. We investigated relationships between platelet-depleted plasma concentrations of serotonin, gastrointestinal symptoms, and motor−sensory function in patients with FC or IBS-C compared with healthy volunteers (controls). We measured platelet-depleted plasma concentrations of serotonin in fasting and fed individuals with IBS-C (n = 23; 19−50 years old), FC (n = 11; 25−46 years old), and controls (n = 23; 20−49 years old) recruited in Manchester, UK. We also quantified abdominal and bowel-related symptoms, rectal sensitivity, oro-cecal transit, and colonic (whole intestine) transit. Patients with IBS-C or FC had similar baseline symptoms, bowel habits, oro-cecal and colonic transit, and fasting concentrations of serotonin and response to meal ingestion. Only patients with IBS-C had increased symptoms after ingestion of a meal (P < .001)—these patients tended to have lower sensory thresholds than patients with FC. Defecation frequency in the combined group of patients with IBS-C or FC correlated inversely with serotonin concentration (r = −0.4; P = .03). Serotonin concentration also correlated with pain threshold (r = 0.4; P = .02) and stool threshold (r = 0.5; P = .06), which correlated inversely with defecation frequency (r = −0.3; P = .10). FC and IBS-C, based on Rome III criteria, are not distinct disorders, symptomatically or physiologically. Instead, they appear to lie in a spectrum of visceral sensitivity modulated by serotonin signaling. Symptom response to meal ingestion should be considered in patient classification.