Introduction

Bile acid diarrhoea (BAD) is a socially debilitating disease characterized by chronic and watery diarrhoea due to excess bile reaching the colon resulting in increased water secretion and motility. Since bile acids may stimulate the release of gut hormones, including peptide tyrosine tyrosine (PYY) implicated in diarrhoeal pathophysiology, we investigated fasting as well as postprandial plasma levels of PYY in BAD and healthy controls.

Aims & Methods

Total PYY concentrations were measured in plasma samples from 12 individuals with colesevelam-treated idiopathic or post-cholecystectomy BAD and 12 healthy controls matched on age, sex and body mass index undergoing two 4-hour liquid mixed meal tests on separate days with either the bile acid sequestrant colesevelam (1,875 mg) or placebo performed in a randomized and double-blinded order. Fasting PYY concentrations, area under the curve (AUC) and baseline-subtracted AUC (bsAUC), respectively, were evaluated.

Results

When comparing the two groups on placebo days, individuals with BAD exhibited higher mean fasting PYY concentrations (95.8 [SEM 12.6] pg/ml vs. 51.5 [12.6] pg/ml, P=0.0095) and AUC (27.1 [3.0] ng/ml × min vs. 16.5 [2.4] ng/ml × min, P=0.0087) whereas bsAUC was similar between groups (4.1 [1.9] ng/ml × min vs. 4.1 [1.6] ng/ml × min, P=0.99). Compared to placebo, colesevelam did not significantly affect PYY levels postprandially in any of the groups.

Conclusion

Here, we demonstrate elevated fasting PYY levels, but normal postprandial PYY responses in individuals with BAD compared to carefully matched healthy controls supporting the notion that bile acids in the gut lumen stimulates the secretion of PYY in individuals with BAD. Whether and how elevated PYY levels contribute to or might counteract BAD pathophysiology remains uncertain.

Disclosure

Filip K. Knop is currently employed by Novo Nordisk A/S, Søborg, Denmark. The remaining authors report no potential conflicts of interest relevant to this abstract.

Introduction

Bile acid diarrhoea (BAD) is a common yet often underdiagnosed cause of chronic diarrhoea. Despite its prevalence, BAD remains frequently overlooked in clinical practice. It is estimated that up to 30% of patients with diarrhoea-predominant irritable bowel syndrome (IBS) have underlying BAD, highlighting the importance of distinguishing between these two conditions for effective management. SeHCAT testing remains the gold standard modality for diagnosing BAD. Management typically involves bile acid sequestrants; however, notable variation exists in management approaches across clinical settings.

Aims & Methods

We retrospectively reviewed all SeHCAT tests performed across Imperial College Hospitals, London between 01/01/2023 – 31/12/2023. Electronic health records were interrogated to extract patient demographics, including age, gender, and ethnicity. The results were analysed to determine the proportion of positive findings, which were subsequently stratified by severity. Corresponding management strategies were recorded to evaluate treatment patterns across clinical specialties.

Results

A total of 313 records were identified, of which 13 were excluded due to incomplete data. The average age of patients was 50 years. The predominant ethnicity was White (50.7%) and the majority of the patients were females (64.7%). Among the 300 remaining records, 154 had positive SeHCAT results with a 7 -day retention between 0 and 15%. Of these, 15.7% were categorised as having moderate bile acid malabsorption, followed by severe (13.3%), mild (11.0%), and borderline (11.3%) cases. The majority of the requests originated from Gastroenterologists (86%), with a smaller proportion from Endobariatrics (5.3%), Hepatobiliary Surgeons (3.7%), Hepatologists (2%), Colorectal Surgeons (1.3%) and other specialities (1.7%). Colestyramine was the most commonly prescribed treatment, with 91% of patients initiated on a 4g once-daily dose. Approximately 26.9% of patients on colestyramine experienced side effects, necessitating a switch to colesevelam. The common side effects noticed were abdominal bloating, abdominal cramps, constipation and reflux. Conversely, 87% of patients on colesevelam continued treatment due to better tolerability, with only 13% exhibiting no clinical improvement. The most frequently prescribed dose was 1.25g daily in 45.3% cases. Among patients with normal SeHCAT results, the majority were diagnosed with diarrhoea-predominant irritable bowel syndrome (47.3%).

Table 1: SeHCAT results

Conclusion

Bile acid diarrhoea continues to be a prevalent factor contributing to chronic diarrhoea in healthcare. While existing treatment modalities have proven effective in managing this condition, they remain poorly tolerated. Our study confirms that colesevelam demonstrates improved tolerability compared to colestyramine.

References

Walters JRF, Arasaradnam RP, Andreyev HJN, UK Bile Acid Related Diarrhoea Network. Diagnosis and management of bile acid diarrhoea: a survey of UK expert opinion and practice. Frontline Gastroenterology 2019; 11:358-363 dx.doi.org/10.1136/flgastro-2019-101301

Introduction

Bile acids malabsorption (BAM) is considered as a one of the possible mechanisms of the irritable bowel syndrome with diarrhea (IBS-D) development. Limitations of BAM first-line treatment – bile acid sequestrants – require investigation of new therapeutic approaches. Probiotic bacteria capable to produce bile salt hydrolase (BSH) are promising in the treatment of IBS-D and assumed BAM

Aims & Methods

The aim of the trial was to compare the effectiveness of combined treatment (a probiotic based on strains of Lactobacillus, Streptococcus, Bifidobacterium, Saccharomyces boulardii and cholestyramine) with cholestyramine monotherapy in the treatment of IBS-D.
Materials and methods: a 12-week randomized trial included 108 patients with IBS-D that were divided into 2 groups: a control group (n=51) receiving only cholestyramine (monotherapy) and an experimental group (n=57) receiving a combination of cholestyramine and the study probiotic (based on strains of Lactobacillus, Streptococcus, Bifidobacterium, Saccharomyces boulardii). Before the start of the treatment, the relative activity (RA) of the BSH of the investigated probiotic was determined using the ultraperformance liquid chromatography with mass spectrometry (UPLC-MS). During the stages of the study, patients were evaluated using clinical scales, including symptoms questionnaires with visual analog scale (VAS).

Results

The BSH RA of the studied probiotic was 2.07±0.06 U/ml compared to 1.0±0.04 U/ml of capsules with L. plantarum and 0.03±0.01 U/ml – with L. plantarum without BSH-genes. In the experimental group, the severity of bloating and visceral sensitivity index values were lower after 8 and 12 weeks, and the value of the type of stool according to the Bristol scale and its daily frequency – after 12 weeks compared to the control group, p<0.05 in all. According to the scale of IBS-adequate relief, the percentage of achieving a clinical effect was higher in the experimental group compared to the control group after 12 weeks, OR = 1.31 (95% CI; 1.03-1.68), p=0.038.

Conclusion

Additional prescribing of a probiotic with BSH producing bacterial strains was more effective in relieving the clinical manifestations of IBS-D and achieving a therapeutic effect compared to cholestyramine monotherapy.

Introduction

The development of colorectal cancer is related to genetic mutations, lifestyle, and diet and eating habits. Fat consumption correlates with increased levels of bile acids in the intestinal lumen, where they stimulate the growth and activity of bacteria that convert primary bile acids into secondary bile acids that have pronounced tumorigenic activity. We assumed that one of the mechanisms of the tumor genesis of bile acids may be a violation of the trans-membrane transport of ions in the intestinal mucosa.

Aims & Methods

Therefore, the aim of this work was to study the effect of taurolithocholic acid 3-sulfate (TLC-S) on the ATPase activity of colorectal cancer samples.The investigation was conducted on colorectal cancer samples of 10 patients. Adjacent samples of healthy tissue served as controls. All patients signed an informed consent to participate in this research. ATPase activity was measured spectrophotometric by the content of P_i in the incubation medium.

Results

We found that the addition of TLC-S to the incubation medium of the subcellular fraction of samples of colorectal cancer patients caused the increase in the specific activity of the Na⁺, K⁺-ATP-ase by 1.5 times (Р≤0.05; n=10) vs to the control (without TLC-S ). In healthy samples the activity of this pump did not change under the influence of TLC-S. However, the addition of TLC-S to the incubation medium of healthy samples of the intestinal mucosa caused a statistically significant decrease in the activity of the basal Mg²⁺-ATPase of the subcellular fraction by 3.6 times vs to the control (Р≤0.05; n=10), but in cancer tissue samples the activity of basal Mg²⁺-ATPase did not change under the influence of TLC-S.

Conclusion

We found that TLC-S causes an increase in the specific activity of the Na⁺,K⁺-ATPase in colorectal cancer samples, and in normal tissue TLC-S reduces the basal Mg²⁺-ATP-ase activity

Disclosure

The authors have no conflict of interest