Are bile acid malabsorption and bile acid diarrhoea important causes of loose stool complicating cancer therapy?

Chronic diarrhoea is a common problem, hence clear guidance on investigations is required. This is an updated guideline from 2003 for the investigations of chronic diarrhoea commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). This document has undergone significant revision in content through input by 13 members of the Guideline Development Group (GDG) representing various institutions. The GRADE system was used to appraise the quality of evidence and grading of recommendations.

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“…Another under-recognised group are those with cancer who have received pelvic chemoradiotherapy as >50% have bile acid diarrhoea. 128 …”

Section: Common Disodersmentioning

confidence: 99%

Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition

Arasaradnam

Brown

Forbes

et al. 2018

Gut

240

222

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“…[40][41][42] Disrupted BA reabsorption in the ileum also precipitates BA malabsorption (BAM)/BA diarrhea (BAD), an under-appreciated and often mis-diagnosed condition in which reduced BA reabsorption-due to genetic mutations (type 2/primary BAM), ileal resection (type 1), or gastrointestinal disease (type 3)-results in abnormally high BA concentrations and water secretion in the colon. 43 Still, steady-state signaling through BA receptors is now recognized as essential for proper regulation of glucose and lipid metabolism, insulin sensitivity, as well as intestinal immunity. 23,29 Even extra-intestinal functions of BAs have begun to emerge, ranging from the ability of BAs to directly promote hematopoietic stem/progenitor cell (HSPC) expansion in the fetal liver, 44 to BAdependent signaling in the CNS that regulates neuroinflammation and neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

Emerging roles of bile acids in mucosal immunity and inflammation

2019

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Bile acids are cholesterol-derived surfactants that circulate actively between the liver and ileum and that are classically recognized for emulsifying dietary lipids to facilitate absorption. More recent studies, however, have revealed new functions of bile acids; as pleotropic signaling metabolites that regulate diverse metabolic and inflammatory pathways in multiple cell types and tissues through dynamic interactions with both germline-encoded host receptors and the microbiota. Accordingly, perturbed bile acid circulation and/or metabolism is now implicated in the pathogenesis of cholestatic liver diseases, metabolic syndrome, colon cancer, and inflammatory bowel diseases (IBDs). Here, we discuss the three-dimensional interplay between bile acids, the microbiota, and the mucosal immune system, focusing on the mechanisms that regulate intestinal homeostasis and inflammation. Although the functions of bile acids in mucosal immune regulation are only beginning to be appreciated, targeting bile acids and their cellular receptors has already proven an important area of new drug discovery.

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“…We have previously shown that this policy yields an abnormal SeHCAT scan in approximately half of patients. 18,19 In addition, patients were asked to rate on a scale of 1-10 their quality of life at present (where 1 = very low and 10 = perfect) and the severity with which their bowel symptoms affect their quality of life (where 1 = not at all and 10 = all the time).…”

Section: Methodsmentioning

confidence: 99%

“…Primary BAD affects approximately 1% of the population. 10 Secondary BAM/BAD -described frequently after upper GI surgery, with pancreatic disease, during chemotherapy or biological therapies for cancer, during and after pelvic radiotherapy, after terminal ileal resection for Crohn's disease or cancer, in those with microscopic colitis and a number of other conditions [11][12][13][14][15][16][17][18][19][20] -affects unquantified, but substantial, numbers of patients. The failure to diagnose this condition -it is frequently misdiagnosed as irritable bowel syndrome -not only means that difficult symptoms are not treated optimally but also impacts on the health economy; many undiagnosed patients undergo, sometimes repeatedly, unnecessary and expensive tests (eg colonoscopy) and are offered ineffective and frequently costly medications.…”

Section: Introductionmentioning

confidence: 99%

The efficacy of a low-fat diet to manage the symptoms of bile acid malabsorption – outcomes in patients previously treated for cancer

et al. 2017

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Dietary fat ingestion triggers bile secretion into the gastrointestinal tract. Bile acid malabsorption affects >1% of the population, causing loose stool and other gastrointestinal symptoms. The diagnosis is frequently missed. Treatments are often considered ineffective. We evaluated low-fat diets for managing gastrointestinal symptoms in these patients. All patients reporting type 6 or 7 stool were offered a selenium-75 homocholic acid taurine (SeHCAT) scan. Prospective data in patients with 7-day scan retention <20% were analysed. Patients requiring a bile acid sequestrant were given this before receiving dietary advice. Patients completed a 7-day food diary before dietetic consultations. Personalised dietary interventions, providing 20% of daily energy from fat, were prescribed. Symptoms were assessed using a modifi ed gastrointestinal symptom rating scale questionnaire before and 4-12 weeks after dietary intervention. A total of 114 patients (49 male, median age 64 years, median body mass index 27 kg/m 2 ) were evaluated. 44% of these patients were taking colesevelam. After dietary intervention, there was statistically signifi cant improvement in abdominal pain and nocturnal defecation (0.2% alpha, p=0.001). Improvement in bowel frequency, urgency, fl atulence, belching, borborygmi and stool consistency were seen, but did not reach statistical signifi cance (p≤0.004-0.031). Dietary intervention is an effective treatment option for patients with symptomatic bile acid malabsorption and should be routinely considered. ABSTRACTThe efficacy of a low-fat diet to manage the symptoms of bile acid malabsorption -outcomes in patients previously treated for cancer

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Are bile acid malabsorption and bile acid diarrhoea important causes of loose stool complicating cancer therapy?

Abstract: BAM/BAD are very common and under-appreciated causes of GI symptoms after cancer treatment. Health professionals should have a low threshold in suspecting this condition, as diagnosis and treatment can significantly improve quality of life.

Cited by 45 publications

References 22 publications

Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition

Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition

Emerging roles of bile acids in mucosal immunity and inflammation

The efficacy of a low-fat diet to manage the symptoms of bile acid malabsorption – outcomes in patients previously treated for cancer

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