AGA technical review on irritable bowel syndrome

The Serotonin Signaling System: From Basic Understanding To Drug Development for Functional GI Disorders

BACKGROUND AND AIMS Post-dysenteric irritable bowel syndrome (PD-IBS) develops in up to 25% of patients following Campylobacter enteritis. Our aim was to define the pathological basis of this subgroup of IBS. METHODS Twenty one patients (group 1) underwent serial rectal biopsy and gut permeability testing following acute Campylobacter enteritis as did 10 PD-IBS patients (group 2) and 12 asymptomatic controls. RESULTS In group 1, enteroendocrine cell (EC) numbers were markedly increased initially and at six and 12 weeks (p r =0.6, p=0.01). At one year, seven subjects (five with persistent loose stools) had rectal biopsies which showed significantly elevated EC, CD3, and IEL counts. In group 2, EC and IEL counts were significantly increased compared with controls (p CONCLUSION Increased EC, T lymphocytes, and gut permeability are acute changes following Campylobacter enteritis which can persist for more than a year and may contribute to PD-IBS.

https://gut.bmj.com/content/gutjnl/47/6/804.full.pdf

Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome

Background: IBS affects 5–11% of the population of most countries. Prevalence peaks in the third and fourth decades, with a female predominance. Aim: To provide a guide for the assessment and management of adult patients with irritable bowel syndrome. Methods: Members of the Clinical Services Committee of The British Society of Gastroenterology were allocated particular areas to produce review documents. Literature searching included systematic searches using electronic databases such as Pubmed, EMBASE, MEDLINE, Web of Science, and Cochrane databases and extensive personal reference databases. Results: Patients can usefully be classified by predominant bowel habit. Few investigations are needed except when diarrhoea is a prominent feature. Alarm features may warrant further investigation. Adverse psychological features and somatisation are often present. Ascertaining the patients’ concerns and explaining symptoms in simple terms improves outcome. IBS is a heterogeneous condition with a range of treatments, each of which benefits a small proportion of patients. Treatment of associated anxiety and depression often improves bowel and other symptoms. Randomised placebo controlled trials show benefit as follows: cognitive behavioural therapy and psychodynamic interpersonal therapy improve coping; hypnotherapy benefits global symptoms in otherwise refractory patients; antispasmodics and tricyclic antidepressants improve pain; ispaghula improves pain and bowel habit; 5-HT 3 antagonists improve global symptoms, diarrhoea, and pain but may rarely cause unexplained colitis; 5-HT 4 agonists improve global symptoms, constipation, and bloating; selective serotonin reuptake inhibitors improve global symptoms. Conclusions: Better ways of identifying which patients will respond to specific treatments are urgently needed.

/pdf/guidelines-on-the-irritable-bowel-syndrome-mechanisms-and-4ocgopleq5.pdf

Guidelines on the irritable bowel syndrome: mechanisms and practical management

Psychosocial aspects of functional gastrointestinal disorders.

Serotoninergic innervation may contribute to the control of colonic motility and to visceral sensation from the large bowel. Indeed, ondansetron hydrochloride, a selective 5-hydroxytryptamine type 3 receptor antagonist, has been shown to slow colonic transit in healthy volunteers. Thus, we wished to determine whether 5-hydroxytryptamine type 3 receptor blockade slows colonic and small bowel transit in patients with diarrhea-predominant irritable bowel syndrome (IBS) and whether symptoms would be ameliorated with drug therapy. Of 14 patients with well-established IBS who entered a randomized, double-blind, placebo-controlled crossover pilot trial of 4 weeks of treatment with ondansetron, 16 mg three times daily, 11 completed the study. A minimal "washout period" of 4 weeks (median, 7 weeks) separated the two phases of the trial because patients were required to have similar symptoms before both periods of the study. Colonic transit tended to be longer during drug therapy than during the placebo trial, but this difference was not significant. Small intestinal transit and orocecal transit were unchanged by the drug. The integrated and peak postprandial increases in neurotensin, peptide YY, and human pancreatic polypeptide in serum were not significantly different in the drug and placebo periods. After treatment with ondansetron, stool consistency improved significantly; however, stool frequency, stool weight, abdominal pain, and the symptom criteria for IBS were not significantly altered by the drug. The results of this pilot study suggest that the motor effects expected with 5-hydroxytryptamine type 3 receptor blockade (namely, slowed colonic transit) may be diminished in some patients with IBS. The subjective improvement in stool consistency may reflect changes in the perception of defecation. Therefore, 5-hydroxytryptamine type 3 receptor blockade warrants further study in diarrhea-predominant IBS.

https://www.mayoclinicproceedings.org/article/S0025-6196(12)60797-6/pdf

Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-predominant irritable bowel syndrome: a pilot study.

https://www.gastrojournal.org/article/0016-5085(91)90014-C/pdf

Variation of muscle tone in the human colon.

In this study, our aim was to test the hypothesis that colonic tone is abnormal in patients with irritable bowel syndrome (IBS). We studied eight patients with IBS and eight age-matched asymptomatic control subjects, in whom tone and motility were measured by an electronic barostat and by pneumohydraulic perfusion manometry, respectively. Tone and motility were recorded from the descending colon for a 14-hour period—3 hours awake, 7 hours asleep, 2 hours fasting after awakening, and 2 hours postprandially. In patients with IBS and in healthy subjects, colonic tone decreased by up to 50% during sleep and increased promptly on awakening. Fasting colonic tone (as quantified by the volume in the barostat balloon) in the awake state was not significantly higher in patients with IBS than it was in healthy subjects (125 ± 13 versus 152 ± 15 ml; P = 0.19). Tone increased postprandially in both study groups, and the increase was greater in healthy subjects than it was in patients with IBS ( P P = 0.05), and the postprandial increase in motility index was greater in the healthy subjects. Preprandially and postprandially, we noted a trend for high-amplitude prolonged contractions to be more frequent in patients with IBS than in healthy subjects. We conclude that colonic tone in patients with IBS showed the same nocturnal and postprandial variations as it did in healthy subjects. In our study, however, we found a clear tendency for preprandial motility to be greater in patients with IBS than in healthy subjects, as exemplified by the higher fasting motility index and the lesser changes that occurred in response to ingestion of food.

https://www.mayoclinicproceedings.org/article/S0025-6196(12)60796-4/pdf

Colonic tone and motility in patients with irritable bowel syndrome.

Human colonic muscle tone varies diurnally and postprandially in predictable ways. Increased tone reduces the capacity of the colon to store contents after a meal, whereas increased distensibility (lesser tone) during sleep enlarges the storage capabilities and may slow transit. We tested the hypothesis that antidiarrhoeal drugs would also alter tone which, in turn, might reduce diarrhoea by facilitating the storage and salvage of fluids. Using a colonic barostat to create low pressure, isobaric colonic distension in healthy volunteers, we found that intravenous atropine (0.01 mg/kg) relaxed the colon during fasting, reduced the postprandial increase in tone, and enhanced relaxation in the late (1-2 hour) postprandial period. Intravenous morphine (0.1 mg/kg) caused variable effects soon after injection but, in fasting subjects, the descending colon relaxed 70-90 minutes after morphine. These changes in colonic motility were not always obvious by conventional manometric recording. Colonic distensibility is increased by antidiarrhoeal drugs and this effect may contribute to their efficacy in slowing colonic transit and augmenting absorption.

https://gut.bmj.com/content/gutjnl/33/4/541.full.pdf

Control of muscle tone in the human colon.

https://www.gastrojournal.org/article/0016-5085(92)90008-M/pdf

Ileocolonic transit does not change after right hemicolectomy

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