Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion

Cholesterol gallstone disease is a worldwide common disease. Cholesterol supersaturation in gallbladder bile is the prerequisite for its pathogenesis, while the mechanism is not completely understood. In this study, we find enrichment of gut microbiota (especially Desulfovibrionales) in patients with gallstone disease. Fecal transplantation of gut microbiota from gallstone patients to gallstone-resistant strain of mice can induce gallstone formation. Carrying Desulfovibrionales is associated with enhanced cecal secondary bile acids production and increase of bile acid hydrophobicity facilitating intestinal cholesterol absorption. Meanwhile, the metabolic product of Desulfovibrionales, H2S increase and is shown to induce hepatic FXR and inhibit CYP7A1 expression. Mice carrying Desulfovibrionales present induction of hepatic expression of cholesterol transporters Abcg5/g8 to promote biliary secretion of cholesterol as well. Our study demonstrates the role of gut microbiota, Desulfovibrionales, as an environmental regulator contributing to gallstone formation through its influence on bile acid and cholesterol metabolism.

Immediate acupuncture with GB34 for biliary colic: protocol for a randomised controlled neuroimaging trial

IntroductionAs the main manifestation of gallstone disease, biliary colic (BC) is an episodic attack that brings patients severe pain in the right upper abdominal quadrant. Although acupuncture has been documented with significance to lead to pain relief, the immediate analgesia of acupuncture for BC still needs to be verified, and the underlying mechanism has yet to be covered. Therefore, this trial aims first to verify the immediate pain-alleviation characteristic of acupuncture for BC, then to explore its influence on the peripheral sensitised acupoint and central brain activity.Methods and analysisThis is a randomised controlled, paralleled clinical trial, with patients and outcome assessors blinded. Seventy-two patients with gallbladder stone disease presenting with BC will be randomised into a verum acupuncture group and the sham acupuncture group. Both groups will receive one session of immediate acupuncture treatment. Improvements in patients’ BC will be evaluated by the Numeric Rating Scale, and the pain threshold of acupoints will also be detected before and after treatment. During treatment, brain neural activity will be monitored with functional near-infrared spectroscopy (fNIRS), and the needle sensation will be rated. Clinical and fNIRS data will be analysed, respectively, to validate the acupuncture effect, and correlation analysis will be conducted to investigate the relationship between pain relief and peripheral–cerebral functional changes.Ethics and disseminationThis trial has been approved by the institutional review boards and ethics committees of the First Teaching Hospital of Chengdu University of Traditional Chinese Medicine, with the ethical approval identifier 2019 KL-029, and the institutional review boards and ethics committees of the First People’s Hospital of Longquanyi District, with the ethical approval identifier AF-KY-2020071. The results of this trial will be disseminated through peer-reviewed publications and conference abstracts or posters.Trial registration numberCTR2000034432.

Іmmunological disorders and colonic dysbiosis in patients with biliary lesions in type 2 diabetes mellitus and obesity

Background. The microbiome plays a crucial role in maintaining homeostasis. The purpose of the research was to study the peculiarities of changes in immunological status and their relationship with colonic dysbiosis in patients with biliary lesions on the background of type 2 diabetes mellitus (DM) and obesity. Materials and methods. The study included 54 patients with type 2 DM and obesity of varying severity, who underwent a comprehensive examination. Two groups of those examined for type 2 DM and obesity were formed, depending on the type of lesion of the biliary system. Thus, group I included 24 patients with chronic acalculous cholecystitis, and group II consisted of 30 patients with gallstone disease. Results. The results of the analysis of the quantitative and qualitative composition of the colonic microflora indicate dysbiotic changes in patients with type 2 DM, obesity, and lesions of the biliary system. More pronounced disorders in the quantitative and qualitative composition of colonic microflora were diagnosed in patients of group II (with type 2 DM and obesity in combination with gallstone disease). The patients of group II significantly more often developed an increase in the number of Enterobacter (14.2 %; p < 0.05), Citrobacter (31.8 %; p < 0.01), Staphylococcus (16.7 %; p < 0.05), and Clostridium (11.8 %; p < 0.05) compared with the data of group I. More pronounced increase in all immunoglobulin parameters was found in patients with gallstone disease associated with type 2 DM and obesity. At the same time, the increase in IgA and IgG levels, which is indisputable evidence of activation of the humoral part of the body’s immunocompetent system, was found in patients with biliary lesions and type 2 DM and obesity. Conclusions. In patients with type 2 DM and obesity in combination with lesions of the biliary system (mainly gallstone disease), changes in the quantitative and qualitative composition of the colonic microflora (a decrease in the number of Bifidobacterium and Lactobacillus and an increase in the concentration of Clostridium, Staphylococci, Proteus, and Klebsiella) were detected. Impairment of immunological status in patients with type 2 DM and obesity in combination with lesions of the biliary tract was diagnosed, which manifested in increased levels of IgA, IgG, IgM, IgG and a decrease in serum C3 and C4 in patients with gallstone disease. The increase in IgA and IgG directly depends on the change in the number of Bifidobacterium and Lactobacillus, Staphylococcus, Clostridium, Proteus in the microbiological examination of feces in patients with type 2 DM and obesity in combination with the biliary system (mainly gallstone disease).

The Possible Association of Non-Alcoholic Fatty Liver Disease with Acute Cholangitis: A Retrospective Multicenter Cohort Study

Non-alcoholic fatty liver disease (NAFLD) is increasingly encountered. It is associated with several comorbid diseases. However, its association with infectious biliary diseases is still unknown. Aims: We aimed to assess whether NAFLD is a risk factor for the development of acute cholangitis among patients with common bile duct (CBD) stones. Methods: We performed a retrospective study, including all patients with a documented diagnosis of CBD stone that had available data on the presence or absence of NAFLD. Descriptive analysis using univariate and multivariate models was used to assess whether an association existed between NAFLD and acute cholangitis. Results: We included 811 patients. Of them, 161 patients presented with acute cholangitis, vs. 650 patients who presented with symptomatic CBD stone without cholangitis. NAFLD was significantly more common in the cholangitis group compared to the non-cholangitis group (15.5% vs. 8.3%, p = 0.01). In univariate analysis, age (Odds ratio (OR) 1.04, p < 0.0001), male gender (OR 1.47, p = 0.03), hypertension (OR 1.81, p = 0.0008), hyperlipidemia (OR 1.59, p = 0.01), and NAFLD (OR 2.04, p = 0.006) were significantly associated with acute cholangitis. In multivariate analysis, NAFLD kept its association with acute cholangitis irrespective of age (OR 2.15, p = 0.005). Conclusions: NALFD showed a significant association with acute cholangitis among patients with a CBD stone. Clinicians should encourage treatment of NAFLD in general, and especially in the setting of gallstone disease.

Overview: prevalence and structure of metabolic diseases of laying chickens, their influence on egg quality and condition of young chickens

The article analyzes and presents statistics on the number of laying hens in Ukraine, production, consumption and import of eggs for the last 5 years, the spread of metabolic diseases of laying hens on the basis of a review of literature sources. Metabolic disorders are the largest group of poultry diseases classified as metabolic diseases and cause significant economic losses. Hepatitis, hepatodystrophy, cirrhosis, liver abscesses, cholecystitis, and gallstone disease are diagnosed in laying hens as a result of impaired carbohydrate, lipid, protein, and mineral metabolism. With a lack or imbalance of calcium and phosphorus or D-hypovitaminosis, in chickens develop diseases such as osteoporosis and hypocalcemia, which reduce egg-laying, quality of hatching eggs and young poultry, and can lead to the death of embryos and adults. Hypovitaminosis (A, D, E) and microelementosis (Co, Cu, Zn, J) in poultry cause decreased immunity, disorders of hormonal system, growth, reproductive functions, egg production, dysfunction of internal organs and nervous system, contribute to the formation of defective eggs, development in embryo of alimentary diseases, which affects the hatchability and quality of young poultry. In view of this, the norms of feeding and keeping poultry are constantly being improved based on an in-depth study of these processes. The subject of this work was a comparative review of the results obtained by various authors on the most common metabolic diseases of laying hens, their impact on productive traits (laying), quality characteristics of eggs, embryogenesis, quality of young laying hens of modern high-yielding crosses. This review of literature sources can serve as a tool for determining the future direction of research, as well as an indicator of its practical application.

Minimally Invasive Treatment for Cholelithiasis

Gallstone disease, cholecysto- and choledocho-lithiasis, is one of the most common digestive diseases. Most patients with symptomatic cholecystolithiasis are recommended to undergo cholecystectomy to alleviate their symptoms like abdominal pain and jaundice. Approximately 10–20% of patients who undergo cholecystectomy for gallstones have choledocholithiasis. Nowadays, endoscopic and/or laparoscopic approaches are widely accepted as the treatment for patients with gallstone. Patients with cholecystolithiasis are usually treated by laparoscopic cholecystectomy, whereas patients with choledocholithiasis are done by endoscopic sphincterotomy (EST) or laparoscopic common bile duct exploration (LCBDE). Additionally, some cases are treated by biliary reconstruction such as biliary enteric anastomosis. In this chapter, currently available laparoscopic approaches as a minimally invasive surgery are introduced and discussed on the basis of pathogenesis of the gallstone.

Efficacy of Hymecromone in Post-Cholecystectomy Patients

Background. The cholecystectomy is the major cause of sphincter of Oddi dysfunction (SOD), that may be classified as post-cholecystectomy syndrome (PCES). Treatment of PCES requires in most of the cases application of selective antispasmodic drugs.Aim. To evaluate efficacy and safety of hymecromone in patients with post-cholecystectomy SOD, to compare standard and reduced doses of hymecromone.Methods. Overall, 26 patients were enrolled in non-interventional comparative study: 2 males, 24 females, aged from 25 to 74 years. All patients underwent cholecystectomy for symptomatic gallstone disease within 1 to 10 years prior to beginning of the study. All patients were diagnosed to have SOD according to Rome IV Diagnostic Criteria for functional biliary sphincter of Oddi disorder (E1b). All patients underwent hymecromone monotherapy for 3 weeks. Patients were randomized to group A and B to receive full-dose or half-dose of the drug respectively.Results. Abdominal pain completely subsided in 85 % of patients, significant improvement was found for bloating and diarrhea. Mild increase in fasting common bile duct (CBD) diameter after treatment (7.23 ± 0.99 vs 6.78 ± 1.01; p = 0.029) was attributed to choleretic action of hymecromone. Hymecromone resulted in significant improvement of CBD response to fatty meal stimulation (ΔCBD): –1.08 ± 0.46 mm vs –0.10 ± 0.33 mm pretreatment (p = 0.016). Degree of improvement was more pronounced in the group A (full-dose) as compared to group B (half-dose) for abdominal pain (Z = 2.74, p = 0.031), bloating (Z = 2.63, p = 0.035) and constipation (Z = 2.61, p = 0.038)Conclusion. Hymecromone demonstrated itself to be an effective and safe drug, that may be applied both in standard and half dose. However, the efficacy of full-dose is higher both for the treatment of biliary pain and dyspeptic symptoms. Transabdominal ultrasound may be applied as a reliable test for both prediction of treatment efficacy and to monitor patients state during treatment course.

THE PRINCIPLES OF DIAGNOSIS AND SURGICAL TREATMENT OF COMPLICATED FORMS OF GALLSTONE DISEASE

Проанализированы за последние три года результаты оперативного лечения 200 больных с осложненными формами желчнокаменной болезни. Доказано, что риск возникновения гнойно-деструктивных форм острого калькулезного холецистита зависит от характера патологического процесса в желчном пузыре. По поводу гнойно-деструктивных форм заболевания при острого калькулезного холецистита оперировано 79,7% больных и 38,9% при необструктивной форме холецистита. Риск интраабдоминальных осложнений зависит от наличия обструкции, выявленное у 18,1% больных с обтурационнной и 5,6% у пациентов с необтурационнной формой. Госпитализация при гнойно-деструктивных формах 63,5% пациентов в первые 2 часа и 85,7% в первые 6 часов от момента заболевания, дает возможность своевременно оперировать больных до развития его интраабдоминальных осложнений. The results of treatment of 200 patients with complicated forms of gallstone disease were analyzed. It is proved that the risk of purulent-destructive forms of acute calculous cholecystitis depends on the nature of the pathological process in the gallbladder. For purulent-destructive forms of the disease in acute calculous cholecystitis, 79.7% of patients and 38.9% of patients with non-obstructive form of cholecystitis were operated on. The risk of intra-abdominal complications depends on the presence of obstruction, identified in 18.1% of patients with obstructive and 5.6% in patients with non-obstructive form. Hospitalization with purulent-destructive forms of 63.5% of patients in the first 2 hours and 85.7% in the first 6 hours from the time of the disease makes it possible to timely operate patients before the development of its intra-abdominal complications.