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Background: The role of food in managing bile acid diarrhoea (BAD) is poorly understood. The present study explored the prevalence of food intolerance amongst adults with BAD. Methods: The study comprised a cross‐sectional survey of adults with BAD determined by the 75selenium homotaurocholic acid test (SeHCAT) living in the UK. Participants anonymously completed an online questionnaire on 39 food items. Frequency of food in general affecting BAD symptoms, as well as frequencies of diarrhoea, abdominal pain, bloating, flatulence and consequential food avoidance after food item ingestion, were assessed. Food group avoidance was also assessed. Results: There were 434 participants who completed the questionnaire between April and May 2021 of whom 80% reported moderate to severe chronic diarrhoea. Food intolerances were reported by 88.0% (95% confidence interval [CI] = 84.6–90.9) of participants. Diarrhoea was reported most frequently after take‐away food, fish and chips, creamy sauces, cream and large quantities of fruit (range 41.0%–33.6%). Lowest frequencies were for potato, avocado, mango, watermelon and pear (range 3.7%–7.4%) for the foods listed in the questionnaire. Similar trends were found for abdominal pain, bloating, flatulence and consequential food avoidance. Symptom‐triggering within 30 min of ingestion was more prevalence than after 30 min for almost all foods. Food group avoidance was highest for fatty foods (81.2%; 95% CI = 77.8–85.3) followed by dairy (53.9%; 95% CI = 49.1–58.7). Conclusions: Perceived food intolerance amongst adults with BAD and persisting diarrhoeal symptoms is high. Important triggers were meals with a higher fat content and higher‐fat dairy products. Diets amongst those with persisting diarrhoeal symptoms may be overly restrictive. Key points: This cross‐sectional online study identified a very high prevalence of perceived food intolerance amongst 434 UK adults living with self‐reported 75selenium homotaurocholic acid test (SeHCAT)‐diagnosed bile acid diarrhoea.Out of 39 foods explored, take‐aways and fish and chips were most frequently blamed for provoking overall gut symptoms and diarrhoea.Potato, avocado, mango, watermelon and pear were perceived to be the least frequently provocative for onset of diarrhoea, abdominal pain, bloating and flatulence.These findings indicate that further studies are needed to better understand the tolerance to dietary fat in bile acid diarrhoea, supporting the inclusion of lower‐fat milk and dairy products, fruits and vegetables. [ABSTRACT FROM AUTHOR]

Only 6 to 8 % of the UK adults meet the daily recommendation for dietary fibre. Fava bean processing lead to vast amounts of high-fibre by-products such as hulls. Bean hull fortified bread was formulated to increase and diversify dietary fibre while reducing waste. This study assessed the bean hull: suitability as a source of dietary fibre; the systemic and microbial metabolism of its components and postprandial events following bean hull bread rolls. Nine healthy participants (53·9 ± 16·7 years) were recruited for a randomised controlled crossover study attending two 3 days intervention sessions, involving the consumption of two bread rolls per day (control or bean hull rolls). Blood and faecal samples were collected before and after each session and analysed for systemic and microbial metabolites of bread roll components using targeted LC-MS/MS and GC analysis. Satiety, gut hormones, glucose, insulin and gastric emptying biomarkers were also measured. Two bean hull rolls provided over 85 % of the daily recommendation for dietary fibre; but despite being a rich source of plant metabolites (P = 0·04 v. control bread), these had poor systemic bioavailability. Consumption of bean hull rolls for 3 days significantly increased plasma concentration of indole-3-propionic acid (P = 0·009) and decreased faecal concentration of putrescine (P = 0·035) and deoxycholic acid (P = 0·046). However, it had no effect on postprandial plasma gut hormones, bacterial composition and faecal short chain fatty acids amount. Therefore, bean hulls require further processing to improve their bioactives systemic availability and fibre fermentation. [ABSTRACT FROM AUTHOR]

Background: Symptomatic gallstones are common. Ursodeoxycholic acid (UDCA) is a bile acid that dissolves gallstones. There is increasing interest in UDCA for symptomatic gallstones, particularly in those unfit for surgery. Method: A UK clinician survey of use and opinions about UDCA in symptomatic gallstones was performed, assessing clinicians' beliefs and perceptions of UDCA effectiveness. A systematic review was performed in accordance with the PRISMA guidelines. PubMed, MEDLINE, and Embase databases were searched for studies of UDCA for symptomatic gallstones (key terms included 'ursodeoxycholic acid'; 'UDCA'; 'biliary pain'; and 'biliary colic'). Information was assessed by two authors, including bias assessment, with independent review of conflicts. Results: Overall, 102 clinicians completed the survey, and 42 per cent had previous experience of using UDCA. Survey responses demonstrated clinical equipoise surrounding the benefit of UDCA for the management of symptomatic gallstones, with no clear consensus for benefit or non-benefit; however, 95 per cent would start using UDCA if there was a randomized clinical trial (RCT) demonstrating a benefit. Eight studies were included in the review: four RCTs, three prospective studies, and one retrospective study. Seven of eight studies were favourable of UDCA for biliary pain. Outcomes and follow-up times were heterogenous, as well as comparator type, with only four of eight studies comparing with placebo. Conclusion: Evidence for UDCA in symptomatic gallstones is scarce and heterogenous. Clinicians currently managing symptomatic gallstone disease are largely unaware of the benefit of UDCA, and there is clinical equipoise surrounding the benefit of UDCA. Level 1 evidence is required by clinicians to support UDCA use in the future. Ursodeoxycholic acid (UDCA) may be beneficial for patients with symptomatic gallstone disease; however, current evidence is heterogenous. Clinicians currently managing symptomatic gallstone disease are largely unaware of the benefit of UDCA, and there is clinical equipoise surrounding the benefit of UDCA. Level 1 evidence is required by clinicians to support UDCA use in the future. [ABSTRACT FROM AUTHOR]

Odevixibat (Bylvay™; Bylvay®) has been approved for progressive familial intrahepatic cholestasis (PFIC) in patients aged ≥ 3 months in the USA and those aged ≥ 6 months in the EU and UK. In the pivotal double-blind placebo-controlled phase 3 PEDFIC 1 study, odevixibat 40 or 120 μg/kg once daily significantly reduced serum bile acids and pruritus. Odevixibat also improved growth, sleep and quality of life parameters compared with placebo in patients with PFIC. The clinical benefits of odevixibat were maintained with continued treatment for up to 72 weeks, according to an interim analysis of the ongoing open-label phase 3 PEDFIC 2 study. Odevixibat is generally well tolerated, with most adverse events being mild or moderate in severity. Longer-term safety data (up to 72 weeks of treatment) revealed no new safety concerns. Plain Language Summary: Progressive familial intrahepatic cholestasis (PFIC) is a rare inherited cholestatic liver disease that is characterized by disturbed bile homeostasis, pruritus, accumulation of biliary components and potentially fatal liver disease. Recently, ileal bile acid transporter (IBAT) inhibitors have emerged as a novel non-surgical approach for the treatment of PFIC. Odevixibat (Bylvay™; Bylvay®), a potent IBAT inhibitor, is approved in the USA for the treatment of pruritus in PFIC for patients aged ≥ 3 months and in the EU and UK for patients aged ≥ 6 months with PFIC. In patients with PFIC, odevixibat significantly decreased serum bile acids and improved pruritus symptoms compared with placebo. Furthermore, improvements in growth and sleep parameters, as well as measures of quality of life were also seen with odevixibat versus placebo. Odevixibat is generally well tolerated, with most adverse events being mild to moderate in severity. Thus, odevixibat is a valuable, effective and generally well-tolerated treatment option for patients with PFIC. [ABSTRACT FROM AUTHOR]

Objective: Investigation of serum bile acid profiles in pregnancies complicated by gestational diabetes mellitus (GDM) in a multi-ethnic cohort of women who are lean or obese., Design: Prospective cohort study., Setting: UK multicentre study., Population: Fasting serum from participants of European or South Asian self-reported ethnicity from the PRiDE study, between 23 and 31 weeks of gestation., Methods: Bile acids were measured using ultra-performance liquid chromatography-tandem mass spectrometry. Log-transformed data were analysed using linear regression in STATA/IC 15.0., Main Outcome Measures: Total bile acids (TBAs), C4, fasting glucose and insulin., Results: The TBAs were 1.327-fold (1.105-1.594) increased with GDM in European women (P = 0.003). Women with GDM had 1.162-fold (1.002-1.347) increased levels of the BA synthesis marker C4 (P = 0.047). In South Asian women, obesity (but not GDM) increased TBAs 1.522-fold (1.193-1.942, P = 0.001). Obesity was associated with 1.420-fold (1.185-1.702) increased primary/secondary BA ratio (P < 0.001) related to 1.355-fold (1.140-1.611) increased primary BA concentrations (P = 0.001). TBAs were positively correlated with fasting glucose (P = 0.039) in all women, and with insulin (P = 0.001) and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (P = 0.001) in women with GDM., Conclusions: Serum BA homeostasis in late gestation depends on body mass index and GDM in ethnicity-specific ways. This suggests ethnicity-specific aetiologies may contribute to metabolic risk in European and South Asian women, with the relationship between BAs and insulin resistance of greater importance in European women. Further studies into ethnicity-specific precision medicine for GDM are required., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Bile acid diarrhoea (BAD) is a widespread gastrointestinal disease that is often misdiagnosed as irritable bowel syndrome and is estimated to affect 1% of the United Kingdom (UK) population alone. BAD is associated with excessive bile acid synthesis secondary to a gastrointestinal or idiopathic disorder (also known as primary BAD). Current licensed treatment in the UK has undesirable effects and has been the same since BAD was first discovered in the 1960s. Bacteria are essential in transforming primary bile acids into secondary bile acids. The profile of an individual's bile acid pool is central in bile acid homeostasis as bile acids regulate their own synthesis. Therefore, microbiome dysbiosis incurred through changes in diet, stress levels and the introduction of antibiotics may contribute to or be the cause of primary BAD. This literature review focuses on primary BAD, providing an overview of bile acid metabolism, the role of the human gut microbiome in BAD and the potential options for therapeutic intervention in primary BAD through manipulation of the microbiome. [ABSTRACT FROM AUTHOR]

Background: While Alzheimer disease (AD) and vascular dementia (VaD) may be accelerated by hypercholesterolemia, the mechanisms underlying this association are unclear. We tested whether dysregulation of cholesterol catabolism, through its conversion to primary bile acids (BAs), was associated with dementia pathogenesis.Methods and Findings: We used a 3-step study design to examine the role of the primary BAs, cholic acid (CA), and chenodeoxycholic acid (CDCA) as well as their principal biosynthetic precursor, 7α-hydroxycholesterol (7α-OHC), in dementia. In Step 1, we tested whether serum markers of cholesterol catabolism were associated with brain amyloid accumulation, white matter lesions (WMLs), and brain atrophy. In Step 2, we tested whether exposure to bile acid sequestrants (BAS) was associated with risk of dementia. In Step 3, we examined plausible mechanisms underlying these findings by testing whether brain levels of primary BAs and gene expression of their principal receptors are altered in AD. Step 1: We assayed serum concentrations CA, CDCA, and 7α-OHC and used linear regression and mixed effects models to test their associations with brain amyloid accumulation (N = 141), WMLs, and brain atrophy (N = 134) in the Baltimore Longitudinal Study of Aging (BLSA). The BLSA is an ongoing, community-based cohort study that began in 1958. Participants in the BLSA neuroimaging sample were approximately 46% male with a mean age of 76 years; longitudinal analyses included an average of 2.5 follow-up magnetic resonance imaging (MRI) visits. We used the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 1,666) to validate longitudinal neuroimaging results in BLSA. ADNI is an ongoing, community-based cohort study that began in 2003. Participants were approximately 55% male with a mean age of 74 years; longitudinal analyses included an average of 5.2 follow-up MRI visits. Lower serum concentrations of 7α-OHC, CA, and CDCA were associated with higher brain amyloid deposition (p = 0.041), faster WML accumulation (p = 0.050), and faster brain atrophy mainly (false discovery rate [FDR] p = <0.001-0.013) in males in BLSA. In ADNI, we found a modest sex-specific effect indicating that lower serum concentrations of CA and CDCA were associated with faster brain atrophy (FDR p = 0.049) in males.Step 2: In the Clinical Practice Research Datalink (CPRD) dataset, covering >4 million registrants from general practice clinics in the United Kingdom, we tested whether patients using BAS (BAS users; 3,208 with ≥2 prescriptions), which reduce circulating BAs and increase cholesterol catabolism, had altered dementia risk compared to those on non-statin lipid-modifying therapies (LMT users; 23,483 with ≥2 prescriptions). Patients in the study (BAS/LMT) were approximately 34%/38% male and with a mean age of 65/68 years; follow-up time was 4.7/5.7 years. We found that BAS use was not significantly associated with risk of all-cause dementia (hazard ratio (HR) = 1.03, 95% confidence interval (CI) = 0.72-1.46, p = 0.88) or its subtypes. We found a significant difference between the risk of VaD in males compared to females (p = 0.040) and a significant dose-response relationship between BAS use and risk of VaD (p-trend = 0.045) in males.Step 3: We assayed brain tissue concentrations of CA and CDCA comparing AD and control (CON) samples in the BLSA autopsy cohort (N = 29). Participants in the BLSA autopsy cohort (AD/CON) were approximately 50%/77% male with a mean age of 87/82 years. We analyzed single-cell RNA sequencing (scRNA-Seq) data to compare brain BA receptor gene expression between AD and CON samples from the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort (N = 46). ROSMAP is an ongoing, community-based cohort study that began in 1994. Participants (AD/CON) were approximately 56%/36% male with a mean age of 85/85 years. In BLSA, we found that CA and CDCA were detectable in postmortem brain tissue samples and were marginally higher in AD samples compared to CON. In ROSMAP, we found sex-specific differences in altered neuronal gene expression of BA receptors in AD. Study limitations include the small sample sizes in the BLSA cohort and likely inaccuracies in the clinical diagnosis of dementia subtypes in primary care settings.Conclusions: We combined targeted metabolomics in serum and amyloid positron emission tomography (PET) and MRI of the brain with pharmacoepidemiologic analysis to implicate dysregulation of cholesterol catabolism in dementia pathogenesis. We observed that lower serum BA concentration mainly in males is associated with neuroimaging markers of dementia, and pharmacological lowering of BA levels may be associated with higher risk of VaD in males. We hypothesize that dysregulation of BA signaling pathways in the brain may represent a plausible biologic mechanism underlying these results. Together, our observations suggest a novel mechanism relating abnormalities in cholesterol catabolism to risk of dementia. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether a particular group of women with intrahepatic cholestasis of pregnancy (ICP), based on their presenting characteristics, would benefit from treatment with ursodeoxycholic acid (UDCA). Design: Secondary analysis of the PITCHES trial (ISRCTN91918806). Setting: United Kingdom. Population or Sample: 527 women with ICP. Methods: Subgroup analyses were performed to determine whether baseline bile acid concentrations or baseline itch scores moderated a woman's response to treatment with UDCA. Main outcome measures: Bile acid concentration and itch score. Results: In women with baseline bile acid concentrations less than 40 μmol/l, treatment with UDCA resulted in increased post‐randomisation bile acid concentrations (geometric mean ratio 1.19, 95% CI 1.00–1.41, P = 0.048). A test of interaction showed no significance (P = 0.647). A small, clinically insignificant difference was seen in itch response in women with a high baseline itch score (–6.0 mm, 95% CI −11.80 to −0.21, P = 0.042), with a test of interaction not showing significance (P = 0.640). Further subgroup analyses showed no significance. Across all women there was a weak relationship between bile acid concentrations and itch severity. Conclusions: There was no subgroup of women with ICP in whom a beneficial effect of treatment with UDCA on bile acid concentration or itch score could be identified. This confirms that its routine use in women with this condition for improvement of bile acid concentration or itch score should be reconsidered. PITCHES: No group of women with ICP has been found in whom UDCA reduces bile acid concentrations or pruritus. PITCHES: No group of women with ICP has been found in whom UDCA reduces bile acid concentrations or pruritus. [ABSTRACT FROM AUTHOR]

Objective: To evaluate enzymatic total serum bile acid quantification as a monitoring strategy for women with intrahepatic cholestasis of pregnancy (ICP) treated with ursodeoxycholic acid (UDCA).Design: Cohort.Setting: One UK university hospital.Population: 29 ICP cases treated with UDCA.Methods: Serial samples were collected prospectively throughout gestation. Total serum bile acids were measured enzymatically and individual bile acids by high-performance liquid chromatography-tandem mass spectrometry. Data were log-transformed and analysed with random effects generalised least square regression.Main Outcome Measures: The relationship between enzymatic total bile acid measurements and individual bile acid concentrations after UDCA treatment.Results: In untreated women, cholic acid was the principal bile acid (51%) and UDCA concentrations were <0.5%, whereas UDCA constituted 60% (IQR 43-69) of serum bile acids following treatment and cholic acid fell to <20%. Changes in the total bile acid measurement reflected similar alterations in the concentrations of the pathologically elevated bile acids, e.g. a two-fold increase in enzymatic total bile acids is accompanied by approximately a two-fold increase in cholic acid and chenodeoxycholic acid at most UDCA doses (P < 0.001). Most of the effects of UDCA on cholic acid occur in the first week of treatment (60% relative reduction, P = 0.025, 95% CI 0.2-0.9, from 10 micromol/l (4.7-17.6) to 3.5 micromol/l (1.4-7.5).Conclusion: Ursodeoxycholic acid becomes the main component of the bile acid measurement after treatment. Enzymatic total bile acid assays are good predictors of both cholic acid and chenodeoxycholic acid, the primary bile acids that are raised prior to treatment.Tweetable Abstract: Ursodeoxycholic acid constitutes approximately 60% of the bile acid measurement and reduces pathological cholic acid in treated women. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics of Great Britain which include the evaluation of bile acid malabsorption, Capsule endoscopy and small bowel.

Background: Cholangiocarcinoma (CC) is a fatal malignancy, the incidence of which is increasing worldwide, with substantial regional variation. Current diagnostic techniques to distinguish benign from malignant biliary disease are unsatisfactory. Metabolic profiling of bile may help to differentiate benign from malignant disease. No previous studies have compared the metabolic profiles of bile from two geographically and racially distinct groups of CC patients. Objectives: This study aimed to compare metabolic profiles of bile, using in vitro proton magnetic resonance spectroscopy, from CC patients from Egypt and the UK, and from patients with CC and patients with non-malignant biliary disease. Methods: A total of 29 bile samples, collected at cholangiography, were analysed using an 11.7-T system. Samples were from eight CC patients in either Egypt ( n= 4) or the UK ( n= 4) and 21 patients with benign biliary disease (choledocholithiasis [ n= 8], sphincter of Oddi dysfunction [ n= 8], primary sclerosing cholangitis [ n= 5]). Results: Bile phosphatidylcholine (PtC) was significantly reduced in CC patients. Egyptian CC patients had significantly lower biliary PtC levels compared with UK patients. Taurine- and glycine-conjugated bile acids (H-26 and H-25 protons, respectively) were significantly elevated in bile from patients with CC compared with bile from patients with benign diseases ( P= 0.013 and P < 0.01, respectively). Conclusions: Biliary PtC levels potentially differentiate CC from benign biliary disease. Reduced biliary PtC in Egyptian compared with UK patients may reflect underlying carcinogenic mechanisms. [ABSTRACT FROM AUTHOR]

Life expectancy in familial hypercholesterolaemia (FH) has been greatly improved by the advent of statin therapy. In the UK, however, these agents are not licensed for use in children. We approached 169 physicians responsible for lipid clinics for information on their practice in young patients, and valid responses were received from 54%. A typical lipid clinic has only 3.5 patients aged under 16 with FH. In boys aged 10-15 years 65% of physicians were prepared to treat with bile acid sequestrants but only 23% with statins. There was greater reluctance to treat in girls of the same age, corresponding figures being 52% and 12%. Despite the efficacy of statins in reducing low-density-lipoprotein cholesterol, these agents are little used in children with FH. Their safety and clinical efficacy should be assessed by a randomized double-blind trial. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics of Great Britain which include pathology, the importance of lymph nodes for the surgical resection of the hilar cholangiocarcinoma and the linking of bile acid malabsorption with the histological abnormalities in colonic mucosa .

It is commonly held that the gall bladder (GB) is not indispensable for life. However, recent studies strongly suggest that GB removal can lead to the development of metabolic syndrome (MetS). With the recent recognition of the role of bile acids (BAs) in systemic metabolic regulation, it is worthwhile to re-examine the function of the GB, which can be regarded as the physiological "pacemaker" of BA flow. Thus, in the present study, we review the role of the GB in BA flow regulation, describe the epidemiologic evidence that associates cholecystectomy with various components of MetS, and discuss the possible mechanism behind these connections in order to demonstrate the pivotal role that GB plays in metabolic regulation. [ABSTRACT FROM AUTHOR]

Reports the use of bile acids in the management of gallstone diseases in Great Britain. Epidemiology of gallstones; Effects of cholecystectomy; Treatment of the disease.

Analyzes the effective treatment for gallstone with bile acids in Great Britain. Reduction of weight for the obese patients; Process for the dissolution of gallstones; Significance on the discovery of chenodeoxycholic acid.