Impact of Bile Acid Diarrhea in Patients With Diarrhea-Predominant Irritable Bowel Syndrome on Symptoms and Quality of Life

BouSaba, Joelle; Sannaa, Wassel; McKinzie, Sanna; Vijayvargiya, Priya; Wang, Xiao Jing; Atieh, Jessica; Zheng, Ting; Brandler, Justin; Taylor, Ann; Busciglio, Irene; Harmsen, William S.; Camilleri, Michael

doi:10.1016/j.cgh.2021.11.035

Cited by 24 publications

(25 citation statements)

References 39 publications

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“…Biochemical features differentiating the two groups (BAD or IBS-D without ABAM) are listed in table 1. As previously reported in the same cohort,30 there was a significant difference in significant diarrhoea between the two groups (BAD (n=44) and IBS-D without ABAM (n=160)). The report of loose or watery stools was significantly more prevalent in BAD compared with IBS-D without ABAM (p=0.002), and specifically loose or watery stools more than 75% of the time were reported by 61% of BAD and 30.9% of patients with IBS-D without ABAM.…”

Section: Resultssupporting

confidence: 85%

Comparison of biochemical, microbial and mucosal mRNA expression in bile acid diarrhoea and irritable bowel syndrome with diarrhoea

Camilleri

Carlson

BouSaba

et al. 2022

Gut

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ObjectiveThere are altered mucosal functions in irritable bowel syndrome with diarrhoea (IBS-D); ~30% of patients with IBS-D have abnormal bile acid (BA) metabolism (ABAM) and diarrhoea (summarised as BAD).AimTo compare biochemical parameters, gastrointestinal and colonic transit, rectal sensation and pathobiological mechanisms in IBS-D without ABAM and in BAD (serum 7C4>52 ng/mL).DesignIn patients with Rome III criteria of IBS-D, we compared biochemical features, colonic transit, rectal sensation, deep genotype of five BA-related genes, ileal and colonic mucosal mRNA (differential expression (DE) analysis) and stool dysbiosis (including functional analysis of microbiome). Results in BAD were compared with IBS-D without ABAM.ResultsCompared with 161 patients with IBS-D without ABAM, 44 patients with BAD had significantly faster colonic transit, lower microbial alpha diversity, different compositional profile (beta diversity) and higher Firmicutes to Bacteroidetes ratio with evidence of decreased expression of bile acid thiol ligase (involved in transformation of primary to secondary BAs) and decreased sulfatases. In BAD (compared with IBS-D without ABAM), terminal ileal biopsies showed downregulation of SLC44A5 (a BA transporter), and ascending colon biopsies showed upregulation in barrier-weakening genes (CLDN2), serine protease inhibitors, immune activation, cellular differentiation and a cellular transporter (FABP6; BA binding). No DE of genes was documented in descending colon biopsies. The two groups had similar rectal sensation.ConclusionThough sharing clinical symptoms with IBS-D, BAD is associated with biological differences and mechanisms that have potential to enhance diagnosis and treatment targeting barrier dysfunction, inflammatory and microbial changes.

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Section: Resultssupporting

confidence: 85%

Comparison of biochemical, microbial and mucosal mRNA expression in bile acid diarrhoea and irritable bowel syndrome with diarrhoea

Camilleri

Carlson

BouSaba

et al. 2022

Gut

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“…Objective BAD testing allows prompt treatment of BAD to eliminate potential symptom confounders, increases adherence to therapy, and can improve the quality of life. 12 …”

Section: Discussionmentioning

confidence: 99%

The Impact of Confounders on Symptom–Endoscopic Discordances in Crohn’s Disease

Rajan

Pan

Mahtani

et al. 2023

Crohn's &Amp; Colitis 360

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Background Discordances between clinical and endoscopic Crohn’s disease (CD) activity indices negatively impact the utility of clinic visits and efficacy assessments in clinical trials. Bile acid diarrhea (BAD) and small intestinal bacterial overgrowth (SIBO) mimic CD symptoms. Aim This study quantified the impact of BAD and SIBO on the relationship between clinical and endoscopic disease activity indices. Methods CD patients with 7α-hydroxy-4-cholesten-3-one (7C4) serum measurements and/or SIBO breath tests and matched clinical and endoscopic scores were included. Clinical remission (stool frequency (SF)≤1 and abdominal pain (AP) score≤1) rates were compared between those with and without A) endoscopic remission, B) BAD (7C4>55ng/mL) and C) SIBO. Results Of 295 CD patients, 219 had SIBO testing and 87 had 7C4 testing. Patients with elevated 7C4 had lower proportions with clinical remission (14% vs. 40%, p=0.007) and SF≤1 (14% vs. 42%, p=0.004) compared to those with normal 7C4. In patients with normal 7C4, higher rates of clinical remission (65% vs. 27%, p=0.01) and SF≤1 (71% vs. 27%, p=0.003) existed in patients with endoscopic remission compared to without endoscopic remission. Conversely, amongst the entire 295 patient cohort, nearly identical clinical remission rates existed between those with and without endoscopic remission (25% vs. 24%, p=0.8), and CDPRO-2 score was not accurate for predicting endoscopic remission (AUC: 0.48; 95% CI 0.42-0.55). SIBO status did not impact clinical remission rates (p=1.0). Conclusion Bile acid diarrhea, but not SIBO, contributed to symptom scores. A relationship between endoscopic inflammation and clinical remission rates only existed in patients without 7C4 elevations.

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“…Patients with BAM complain an increased frequency of watery chronic diarrhea (80%) and fecal urgency (85%), associated with abdominal discomfort, which can include abdominal pain, bloating and fecal incontinence [ 13 ]. According to a recent study, patients with IBS-D with BAD reported a greater impact on bowel and somatic symptoms and quality of life compared with those without BAD, mainly due to more severe and frequent diarrhea along with urgency, which was supported by an increased need of toilet proximity [ 91 ]. In addition, patients with BAD reported an increased use of antidiarrheals, bile acid binders and antacid secretory agents than those without [ 91 ].…”

Section: Clinical Manifestationsmentioning

confidence: 99%

“…According to a recent study, patients with IBS-D with BAD reported a greater impact on bowel and somatic symptoms and quality of life compared with those without BAD, mainly due to more severe and frequent diarrhea along with urgency, which was supported by an increased need of toilet proximity [ 91 ]. In addition, patients with BAD reported an increased use of antidiarrheals, bile acid binders and antacid secretory agents than those without [ 91 ]. Affected individuals may also report systemic symptoms including fatigue, dizziness and feeling of fainting [ 65 ].…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Pathophysiology and Clinical Management of Bile Acid Diarrhea

Marasco

Cremon

Barbaro

et al. 2022

JCM

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Bile acid malabsorption (BAM) represents a common cause of chronic diarrhea whose prevalence is under-investigated. We reviewed the evidence available regarding the pathophysiology and clinical management of bile acid diarrhea (BAD). BAD results from dysregulation of the enterohepatic recirculation of bile acids. It has been estimated that 25–33% of patients with functional diarrhea and irritable bowel syndrome with diarrhea have BAM. Currently, the selenium homotaurocholic acid test is the gold standard for BAD diagnosis and severity assessment. However, it is an expensive method and not widely available. The validation of the utility in the clinical practice of several other serum markers, such as 7α-hydroxy-4-cholesten-3-one (C4) and the fibroblast growth factor 19 (FGF19) is ongoing. The first-line treatment of patients with BAD is bile acid sequestrants. Patients that are refractory to first-line therapy should undergo further diagnostics to confirm the diagnosis and to treat the underlying cause of BAD. An early and correct diagnosis of BAD would improve patient’s quality of life, avoiding additional diagnostic tests that burden health care systems. Considering the limited availability and tolerability of specific medications for BAD treatment, future research is awaited to identify other therapeutic approaches, such as gut microbiota modulating therapies.

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Impact of Bile Acid Diarrhea in Patients With Diarrhea-Predominant Irritable Bowel Syndrome on Symptoms and Quality of Life

Cited by 24 publications

References 39 publications

Comparison of biochemical, microbial and mucosal mRNA expression in bile acid diarrhoea and irritable bowel syndrome with diarrhoea

Comparison of biochemical, microbial and mucosal mRNA expression in bile acid diarrhoea and irritable bowel syndrome with diarrhoea

The Impact of Confounders on Symptom–Endoscopic Discordances in Crohn’s Disease

Pathophysiology and Clinical Management of Bile Acid Diarrhea

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