Risk Of Gallstone Disease Research Articles

Association between Neutrophil-to-high-density lipoprotein-cholesterol ratio and gallstones: insights from the national health and nutrition examination survey (2017–2020)

BackgroundInflammatory responses and lipid metabolism make vital impacts on the development of gallstones. This study investigated the relationship between gallstone disease (GSD) and the neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) in American patients with gallstones.MethodsThe data analyzed were sourced from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) and comprised of participants with complete data on GSD and NHR. The relationship between NHR and GSD was evaluated with weighted multivariable logistic regression analysis. Additionally, subset analyses, interaction tests, smoothed curve fitting, and threshold effect analyses were conducted.ResultsAmong the 7894 participants analyzed in this study, the prevalence of GSD was 10.98%, and the average NHR value was 3.41 ± 0.06. The fully adjusted multivariable logistic regression results demonstrated an obvious positive association between NHR and the likelihood of GSD (OR = 1.09, 95% CI: 1.01, 1.16; P = 0.0197). Consistency of this association was confirmed through subset analyses and interaction tests across various subgroups, including those categorized by smoking status and asthma. Furthermore, smoothed curve fitting and threshold effect analyses revealed a nonlinear relationship with a threshold of 2.86.ConclusionsNHR shows a positive relationship to an increased likelihood of GSD among Americans. It can act as an easy and cost-effective tool for the early detection and management of individuals at risk for GSD.

Risk Factors for Gallstones in Crohn's Disease: A Systematic Review and Meta-Analysis.

Crohn's disease (CD) have an increased risk of gallstone disease. We aimed to systematically evaluate the prevalence rate and relevant risk factors of gallstones in CD patients. A comprehensive search of PubMed, Embase, and Web of Science databases from inception to September 10, 2023, identified studies investigating risk factors for gallstone development among CD patients. Gender, age, body mass index, disease duration, disease site, stenosis, prior surgery, hospitalization times, corticosteroids, immunomodulators, and total parenteral nutrition (TPN) were assessed as potential risk factors. Odds ratios (OR) and confidence intervals (CI) were calculated. Among 1184 articles, 11 observational studies (3588 patients) were included. The prevalence of CD patients with gallstones was approximately 14.7%. Factors significantly associated with increased gallstone risk included Age ≥ 40years old (OR 3.06, 95% CI 2.09- 4.48), disease duration > 15years (OR 3.01, 95% CI 2.06-4.42), lifetime surgery(OR 2.50, 95% CI 1.99-3.12), disease located in ileocolon (OR 1.38, 95% CI 1.04-1.83) and ileocecal(OR 1.93, 95% CI 1.16-3.21), multiple hospitalizations(OR 4.26, 95% CI 2.43-7.46), corticosteroid treatments(OR 2.65, 95% CI 1.52-4.63), immunomodulator therapy(OR 1.94, 95% CI 1.12-3.38), and TPN use(OR 2.66, 95% CI 1.29-5.51). Sex, stenosis, overweight, or low weight did not significantly increase the risk of gallstone developing. Age, long disease duration, specific disease locations (ileocolon, ileocecal), surgery, number of hospitalizations, corticosteroids, immunomodulator therapy, and TPN were identified as factors that increased the risk of gallstones in CD patients. About 14.7% of CD patients experience gallstones, so raising awareness and implementing prevention are needed. PROSPERO (CRD42023449299).

Sex disparities in gallstone disease: insights from the MAUCO prospective population-based cohort study

ObjectiveTo investigate factors associated with the prevalence and incidence of gallstone disease (GSD) in women and men of the MAUCO population-based prospective cohort.Design8948 MAUCO participants (aged 38–74 years) underwent abdominal...

Hepatic Insulin Resistance Increases Risk of Gallstone Disease in Indigenous Americans in the Southwestern United States.

Animal models indicate that hepatic insulin resistance (IR) promotes cholesterol gallstone disease (GSD). We sought to determine whether hepatic and whole-body IR is associated with incident GSD. At baseline, 450 Southwestern Indigenous American adults without GSD were included. Participants had a 2-step hyperinsulinemic-euglycemic clamp with glucose tracer at submaximal and maximal insulin stimulation (240 and 2,400 pmol/m 2 /min) for whole-body IR (M-low and M-high) and hepatic glucose production (HGP) before and during submaximal insulin infusion (HGP-basal and HGP-insulin). Incident GSD was identified during follow-up visits conducted at ∼2-year intervals. The associations of HGP (basal, insulin, and % suppression), M-low, and M-high with risk of GSD were assessed by Cox regression models adjusted for age, sex, body fat (%), glucose, and insulin. Sixty participants (13%) developed GSD (median follow-up: 11.6 years). Participants who developed GSD were of similar age and whole-body IR as those who did not ( P 's > 0.07) but were more likely to be female; have higher body fat, higher HGP-basal, and HGP-insulin; and lower % suppression of HGP ( P 's < 0.02). In separate adjusted models, higher HGP-insulin and lower % suppression of HGP were associated with increased risk for GSD (hazard ratio [HR] per SD: HR 1.38, 95% CI 1.12-1.69, P = 0.002; HR 1.41, 95% CI 1.16-1.72, P = 0.0007). HGP-basal, M-low, and M-high were not associated with GSD in adjusted models ( P 's > 0.22). Resistance to insulin suppression of HGP increases risk for GSD. Hepatic IR is a link between GSD and other conditions of the metabolic syndrome.

Multi-biobank Mendelian randomization analyses identify opposing pathways in plasma low-density lipoprotein-cholesterol lowering and gallstone disease

Plasma low-density lipoprotein (LDL)-cholesterol is positively associated with coronary artery disease risk while biliary cholesterol promotes gallstone formation. Different plasma LDL-cholesterol lowering pathways may have distinct effects on biliary cholesterol and thereby gallstone disease risk. We conducted a Mendelian randomization (MR) study using data from the UK Biobank (30,547 gallstone disease cases/336,742 controls), FinnGen (34,461 cases/301,383 controls) and Biobank Japan (9,305 cases/168,253 controls). We first performed drug-target MR analyses substantiated by colocalization to investigate the effects of plasma LDL-cholesterol lowering therapies on gallstone disease risk. We then performed clustered MR analyses and pathway analyses to identify distinct mechanisms underlying the association of plasma LDL-cholesterol with gallstone disease risk. For a 1-standard deviation reduction in plasma LDL-cholesterol, genetic mimics of statins were associated with lower gallstone disease risk (odds ratio 0.72 [95% confidence interval 0.62, 0.83]), but genetic mimics of PCSK9 inhibitors and targeting apolipoprotein B were associated with higher risk (1.11 [1.03, 1.19] and 1.23 [1.13, 1.35]). The association for statins was supported by colocalization (posterior probability 98.7%). Clustered MR analyses identified variant clusters showing opposing associations of plasma LDL-cholesterol with gallstone disease risk, with some evidence for ancestry-and sex-specific associations. Among variants lowering plasma LDL-cholesterol, those associated with lower gallstone disease risk were mapped to glycosphingolipid biosynthesis pathway, while those associated with higher risk were mapped to pathways relating to plasma lipoprotein assembly, remodelling, and clearance and ATP-binding cassette transporters. This MR study provides genetic evidence that different plasma LDL-cholesterol lowering pathways have opposing effects on gallstone disease risk.

Association between different dietary carbohydrates and risk of gallstone: a case-control study in Iranian adults

PurposeDietary components have been mentioned as modifiable risk factors in the development of gallstone disease (GSD), but it has been less addressed. The present study aimed to investigate the potential association between different types of dietary carbohydrate and the risk of gallstone.Design/methodology/approachIn this case-control study 189 patients diagnosed with GSD as a case group and 342 people as a control group were enrolled. Dietary intake of the participants was collected through a 168-item semi-quantitative food frequency questionnaire. Total intakes of calories, macronutrients and different types of carbohydrate were estimated. Crude and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between carbohydrate intake and GSD.FindingsPatients with gallstone consumed significantly more fructose and sucrose and less fiber. After fully adjustment, the logistic regression indicated significant association between GSD with dietary intake of total carbohydrate (OR = 1.65, 95% CI: 1.1–2.4, p = 0.009), sugar (OR = 1.23, 95% CI: 0.8–1.7, p = 0.014), fructose (OR = 2.5, 95% CI: 1.7–3.9, p < 0.001), glucose (OR = 1.9, 95% CI: 1.3–2.9, p = 0.002) and sucrose (OR = 1.37, 95% CI: 0.9–1.6, p = 0.042). Also, increasing intakes of lactose, galactose and maltose were associated with a decrease in the risk of GSD, but not statistically significant, although lactose was close to significance (OR = 0.71, 95% CI: 0.48–1, p = 0.051).Originality/valueThere is a positive and significant relationship between total carbohydrate, sugar, fructose, glucose and sucrose intake and the occurrence of gallstone.

Ultraprocessed food consumption and risk of gallstone disease: analysis of 3 prospective cohorts

BackgroundMajority of dietary intake in United States adults comes from ultraprocessed foods (UPFs), which have been linked to several adverse health outcomes. Gallstone disease is highly prevalent and constitutes a significant burden to the United States health system but remains understudied. ObjectivesThis study aimed to investigate the association between UPF consumption and incident gallstone disease risk. MethodsIn this analysis, 44,149 males in the Health Professionals’ Follow-up Study (HPFS: 1986–2022), 71,145 females in the Nurses’ Health Study (NHS: 1986–2021), and 90,932 females in the NHS II (1991–2021) were prospectively followed. Dietary intake was quadrennially assessed with semiquantitative food frequency questionnaires and used to identify UPFs. The primary outcome was defined as cholecystectomy. Cox proportional hazards model was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). ResultsBaseline median age was 54 y in HPFS, 53 y in NHS, and 36 y in NHS II. We identified 32,374 incident gallstone disease cases over 5,077,059 person-years. Participants in the highest UPF quintile had a higher incidence of gallstone disease than those in the lowest quintile (aHR: 1.29; 95% CI: 1.24, 1.36; P < 0.001). Incremental risk of incident gallstone disease was 2.8% per daily serving (95% CI: 2.4%, 3.2%; P < 0.001). This risk was driven by sugar-sweetened beverages and artificially sweetened beverages on UPF subgroup analyses. The proportion of risk mediated by obesity was 12.8% (95% CI: 7.7%, 20.5%; P < 0.001) in HPFS, 14.3% (95% CI: 10.4%, 19.4%; P < 0.001) in NHS, and 39.4% (95% CI: 31.2%, 48.1%; P < 0.001) in NHS II. The partial population attributable risk was estimated at 15.9% (95% CI: 13.4%, 18.3%). ConclusionsUPF consumption is associated with a higher risk of gallstone disease, particularly consumption of sugar-sweetened beverages and artificially sweetened beverages. A substantial proportion of this risk is potentially mediated by obesity in younger females.

Food consumption patterns and risk of gallstone disease (GD): Case and Control Study in Rosario Argentina.

Nutritional exposure is considered the main environmental influence that contributes to gallstone disease (GD). The aim of this study was to determine food intakes patters and estimate risk of GD. A nested case-control study was carried out within the framework of a previous screening study conducted on a representative sample in Rosario, Argentina. Participants underwent a personal interview. Average amount of each food intake and quantity nutrients were estimated applying a food-frequency questionnaire. Food consumption patterns were identified by principal component analysis, and logistic regression analysis was used to estimate risks. The sample was conformed by 51 cases and 69 controls. Two dietary patterns were identified. Cases were characterised by the unhealthy intake pattern (high intakes of animal fats, sugar, cereals, grains, cold cuts, processed meats, chicken with skin, fat beef and low intake of red vegetables and yellows, cabbages, fruits and fish). Controls were characterised by the healthy intake pattern (high intake of skinless chicken, nuts, lean beef, vitamin A and C rich fruits, and low consumption of chicken with skin, green leaves vegetables and sprouts). The unhealthy pattern showed an increased risk of developing GD while healthy patter behaved as a protective factor.

Association between triglyceride glucose index-related indices with gallstone disease among US adults

BackgroundTriglyceride glucose (TyG) index combined with obesity-related indicators [triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC)], represents emerging methodologies for assessing insulin resistance. The objective of this investigation was to explore the correlation between TyG-related indices and gallstone disease.MethodsThe study included 3740 adults from the 2017–2020 period of the National Health and Nutrition Examination Survey. TyG-BMI, TyG-WC, and TyG-WHtR were integrated as both continuous and categorical variables within the multivariate logistic model, respectively to evaluate the connection between various TyG-related indices and gallstone disease. Additionally, restriction cubic splines and subgroup analysis were employed to deepen our understanding of this relationship.ResultsWhen analyzed as continuous variables, positive correlations were observed between TyG-BMI, TyG-WC, TyG-WHtR and gallstone disease. The OR(95%CI) were 1.063(1.045,1.082) for TyG-BMI (per 10-unit), 1.026(1.018,1.034) for TyG-WC (per 10-unit) and 1.483(1.314,1.676) for TyG-WHtR (per 1-unit), respectively. When categorized into quartiles, these three TyG-related indices still show statistically significant associations with gallstone disease. Descending in order, the diagnostic capability for gallstone disease is demonstrated as follows: TyG-WHtR (AUC = 0.667), TyG-BMI (AUC = 0.647), and TyG-WC (AUC = 0.640).ConclusionThere were significantly positive associations between TyG-related indices, including TyG-BMI, TyG-WC, and TyG-WHtR, and gallstone disease. Of these indices, TyG-WHtR demonstrated the most favorable performance in identifying the risk of gallstone disease.

Association between plant-based dietary index and gallstone disease: A cross sectional study from NHANES.

The relationship between plant-based diets and gallstone disease has been debated. This study aimed to shed light on the association between plant-based dietary index and the risk of developing gallstone disease. Eligible participants were selected from National Health and Nutrition Examination Survey (NHANES) 2017-2020. Three plant-based diet indexes (PDI, healthy PDI, unhealthy PDI) were calculated using data from two NHANES 24-h dietary recall interviews. Restricted Cubic Spline and multivariate logistic regression were used to analyze the associations. Subgroup analysis was adopted to make the results more robust. A total of 5673 eligible participants were analyzed. After adjusting for various confounding variables, uPDI was positively associated with gallstone disease (OR = 1.53, 95%CI: 1.02-2.29). No association was found between PDI/hPDI and gallstone disease (p > 0.05). The results of subgroup analysis did not show any positive association between uPDI and gallstones in specific groups. Our study shows that the elevated uPDI are linked to a higher risk of gallstone disease.

SLC10A1 rs2296651 variant (S267F mutation) predicts biochemical traits, hepatitis B virus infection susceptibility and the risk of gallstone disease.

Sodium taurocholate co-transporting polypeptide (NTCP), a bile acid transporter, plays a crucial role in regulating bile acid levels and influencing the risk of HBV infection. Genetic variations in the SLC10A1 gene, which encodes NTCP, affect these functions. However, the impact of SLC10A1 gene variants on the metabolic and biochemical traits remained unclear. We aimed to investigate the association of SLC10A1 gene variants with the clinical and biochemical parameters, and the risk of different HBV infection statuses and gallstone disease in the Taiwanese population. Genotyping data from 117,679 Taiwan Biobank participants were analyzed using the Axiom genome-wide CHB arrays. Regional-plot association analysis demonstrated genome-wide significant association between the SLC10A1 rs2296651 genotypes and lipid profile, gamma glutamyl transferase (γGT) level and anti-HBc-positivity. Genotype-phenotype association analyses revealed significantly lower total cholesterol, low-density lipoprotein (LDL) cholesterol and uric acid levels, a higher γGT level and a higher gallstone incidence in rare rs2296651-A allele carrier. Participants with the rs2296651 AA-genotype exhibited significantly lower rates of anti-HBc-positivity and HBsAg-positivity. Compared to those with the GG-genotype, individuals with non-GG-genotypes had reduced risks for various HBV infection statuses: the AA-genotype showed substantially lower risks, while the GA-genotype demonstrated modestly lower risks. Predictive tools also suggested that the rs2296651 variant potentially induced protein damage and pathogenic effects. In conclusion, our data revealed pleiotropic effects of the SLC10A1 rs2296651 genotypes on the levels of biochemical traits and the risk of HBV infection and gallstone disease. This confirms SLC10A1's versatility and implicates its genotypes in predicting both biochemical traits and disease susceptibility.

The Association between Healthy Eating Index-2015 and Serum Metabolic Parameters in Women with Gallstone Disease: A Case-Control Study.

One of the most prevalent gastrointestinal tract ailments is gallstone disease (GD). Diet has been acknowledged as a modifiable GD risk factor. The Healthy Eating Index (HEI) is a scale for evaluating the quality of diets; therefore, this study aimed to determine whether the HEI-2015 score was associated with serum metabolic parameters in women with GD. This case-control study was conducted on a sample of 75 women diagnosed with GD and 75 healthy women at the Gastroenterology and Hepatology Clinic of Shahid Beheshti University of Medical Science in Tehran, Iran. Standard laboratory methods were employed to measure the biochemical parameters. The participants' habitual dietary intake was assessed using a validated food frequency questionnaire (FFQ). The HEI-2015 score was computed for all participants. The study employed multivariate logistic regression to identify the optimal predictor of GD. The Pearson Correlation was employed to determine the correlation between the HEI-2015 and serum metabolic parameters. The study found a significant negative association between the risk of GD and serum HDL-c (OR: 0.84; 95% CI: 0.76-0.95, P=0.008). Moreover, a significant positive association was detected between HOMAIR (OR: 3.27; 95% CI: 1.16-9.19, P=0.025), and the risk of GD. The study did not find a statistically significant correlation between the HEI-2015 and serum parameters. While an association was discovered between certain serum metabolic parameters and the risk of GD, the results do not provide a significant association between serum metabolic parameters and HEI-2015 score.

The ABCG8 polymorphism increases the risk of gallbladder cancer in the general population and gallstones in obese patients from Poland.

Gallstone disease (GD) is common but remains asymptomatic in most cases. However, gallstones can lead to complications like choledocholithiasis or gallbladder cancer. In this study, we analyse the common genetic risk factor for GD, the p.D19H variant in the sterol transporter ABCG8, in Polish patients with gallstones and gallbladder cancer. Three adult cohorts were prospectively recruited: 65 patients with gallbladder cancer, 170 obese individuals scheduled for bariatric surgery and 72 patients who underwent endoscopic retrograde cholangiopancreatography due to recurrent choledocholithiasis. The control cohort consisted of 172 gallstone-free adults. The ABCG8 p.D19H (rs11887534) polymorphism was genotyped using TaqMan assays. The minor allele frequency (MAF) of the ABCG8 p.D19H polymorphism was significantly (p = .02) higher among cases with either gallstones or gallbladder cancer (MAF = 8.4%) as compared to controls (MAF = 4.0%). The highest frequency of the risk allele was detected in patients with gallbladder cancer (18.5%) and obese patients with GD (17.5%), followed by individuals with choledocholithiasis (13.9%). Notably, the p.19H variant was associated with an increased risk of developing gallbladder cancer (OR 2.76, 95% CI 1.16-6.54, p = .01) and an increased risk of GD in obese individuals scheduled for bariatric surgery (OR = 2.70, 95% CI 1.05-6.49, p = .03), but did not significantly affect the risk of choledocholithiasis. The ABCG8 p.D19H common risk variant increases the risk of developing gallbladder cancer in Central Europeans and enhances the risk of gallstones in the obese. Carriers of the p.D19H variant might benefit from personalized preventive strategies, particularly regarding gallbladder cancer.

Association of pro-inflammatory diet with increased risk of gallstone disease: a cross-sectional study of NHANES January 2017-March 2020.

Gallstone disease (GSD) is a major public health problem worldwide. The dietary inflammatory index (DII) and the energy-adjusted DII (E-DII) have been used to describe dietary inflammatory potential. The current study sought to investigate the pro-inflammatory role of diet on GSD among outpatients in the United States. Cross-sectional data from 7,334 individuals older than 20 years who participated in the National Health and Nutrition Examination Survey (NHANES) from January 2017 to March 2020 were obtained. The relationship between GSD and DII was assessed using self-reported data. An association between DII and the risk of GSD was determined using sample-weighted logistic regression and restricted cubic splines (RCS). Subgroup analyzes were conducted to assess the interaction between DII and related factors. Sensitivity analysis was further used to confirm the stability of the relationship. To control for the effect of total energy intake, E-DII was calculated and analyzed. A total of 10.5% of the study participants had GSD. The DII ranged from -5.52 to 5.51, and the median DII was significantly higher for participants with GSD than those without (1.68 vs. 1.23, p < 0.001). There was a significant and stable positive relationship between DII and GSD in adjusted models (OR 1.10, 95% CI 1.00-1.20). In the fully adjusted model, subjects with DII scores in the highest tertile were more likely to have GSD than those in the lowest tertile (OR 1.52, 95% CI 1.19-1.93). An apparent dose-response association between DII and GSD was detected. The association between E-DII and GSD remained stable. Higher DII/E-DII scores linked to the intake of a pro-inflammatory diet were positively associated with a higher risk of GSD. These findings suggest that pro-inflammatory dietary patterns can promote the formation of gallstones.

Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses.

General obesity is a well-established risk factor for gallstone disease (GSD), but whether central obesity contributes additional independent risk remains controversial. We aimed to comprehensively clarify the effect of body fat distribution on GSD. We first investigated the observational association of central adiposity, characterized by waist-to-hip ratio (WHR), with GSD risk using data from UK Biobank (N=472,050). We then explored the genetic relationship using summary statistics from the largest genome-wide association study of GSD (ncase=43,639, ncontrol=506,798) as well as WHR, with and without adjusting for body mass index (BMI) (WHR: n=697,734; WHRadjBMI: n=694,649). Observational analysis demonstrated an increased risk of GSD with one unit increase in WHR (HR=1.18, 95%CI=1.14-1.21). A positive WHR-GSD genetic correlation ( =0.41, P=1.42×10-52) was observed, driven by yet independent of BMI (WHRadjBMI: =0.19, P=6.89×10-16). Cross-trait meta-analysis identified four novel pleiotropic loci underlying WHR and GSD with biological mechanisms outside of BMI. Mendelian randomization confirmed a robust WHR-GSD causal relationship (OR=1.50, 95%CI=1.35-1.65) which attenuated yet remained significant after adjusting for BMI (OR=1.17, 95%CI=1.09-1.26). Furthermore, observational analysis confirmed a positive association between general obesity and GSD, corroborated by a shared genetic basis ( =0.40, P=2.16×10-43), multiple novel pleiotropic loci (N=11) and a causal relationship (OR=1.67, 95%CI=1.56-1.78). Both observational and genetic analyses consistently provide evidence on an association of central obesity with an increased risk of GSD, independent of general obesity. Our work highlights the need of considering both general and central obesity in the clinical management of GSD.

Observational and genetic analyses clarify the relationship between type 2 diabetes mellitus and gallstone disease.

The relationship between type 2 diabetes mellitus (T2DM) and gallstone disease (GSD) have been incompletely understood. We aimed to investigate their phenotypic and genetic associations and evaluate the biological mechanisms underlying these associations. We first evaluated the phenotypic association between T2DM and GSD using data from the UK Biobank (n>450,000) using a prospective observational design. We then conducted genetic analyses using summary statistics from a meta-analysis of genome-wide association studies of T2DM, with and without adjusting for body mass index (BMI) (Ncase=74,124, Ncontrol=824,006; T2DMadjBMI: Ncase=50,409, Ncontrol=523,897) and GSD (Ncase=43,639, Ncontrol=506,798). A unidirectional phenotypic association was observed, where individuals with T2DM exhibited a higher GSD risk (hazard ratio (HR)=1.39, P<0.001), but not in the reverse direction (GSD→T2DM: HR=1.00, P=0.912). The positive T2DM-GSD genetic correlation (rg=0.35, P=7.71×10-23) remained even after adjusting for BMI (T2DMadjBMI: rg=0.22, P=4.48×10-10). Mendelian randomization analyses provided evidence of a unidirectional causal relationship (T2DM→GSD: odds ratio (OR)=1.08, P=4.6×10-8; GSD→T2DM: OR=1.02, P=0.48), even after adjusting for important metabolic confounders (OR=1.02, P=0.02). This association was further corroborated through a comprehensive functional analysis reflected by 23 pleiotropic single nucleotide polymorphisms, as well as multiple neural and motor-enriched tissues. Through comprehensive observational and genetic analyses, our study clarified the causal relationship between T2DM and GSD, but not in the reverse direction. These findings might provide new insights into prevention and treatment strategies for T2DM and GSD.

Gut microbiota, circulating metabolites, and gallstone disease: a Mendelian randomization study

BackgroundThe link between Gut microbiota (GM) and Gallstone disease (GSD) is well established, but it is not clear whether there is a causal relationship between the two associations.MethodsWe conducted bidirectional Mendelian randomization (MR) analyses, leveraging aggregated data from the Genome-Wide Association Study (GWAS) of GM and Circulating Metabolites. Our primary objective was to investigate the causal interplay between intestinal flora and GSD. Additionally, we performed mediational analyses, two-step MR, and multivariate MR to uncover the potential mediating effect of circulating metabolites in this relationship.ResultOur study has revealed a causal relationship between GSD and six distinct bacterial groups. Genetically predicted Class Bacilli (Odds Ratio (OR): 0.901, 95% Confidence Interval (95% CI): 0.825–0.985; p = 0.021), Order Lactobacillales (OR: 0.895, 95% CI: 0.816–0.981; p = 0.017), and Genus Coprococcus 2 (OR: 0.884, 95% CI: 0.804–0.973; p = 0.011) were inversely associated with the risk of GSD. Conversely, the Genus Clostridiumsensustricto1 (OR: 1.158, 95% CI: 1.029–1.303; p = 0.015), Genus Coprococcus3 (OR: 1.166, 95% CI: 1.024–1.327; p = 0.020), and Genus Peptococcus (OR: 1.070, 95% CI: 1.017–1.125; p = 0.009) were positively associated with the risk of GSD. Moreover, our findings suggest that the positive influence of the Genus Peptococcus on GSD may be mediated through Omega-3 polyunsaturated fatty acids (PUFA).ConclusionThis study reinforces the connection between the gut microbiome and the risk of GSD while also unveiling the mediating role of Omega-3 PUFA in the causal relationship between these factors.

Foods and nutrients consumption and the risk of gallstone disease: A nested case-control study in Rosario, Argentina

The etiology of Gallstone Disease (GD) is multivariate and it involves genetics and environmental factors. Nutritional exposure is considered the main environmental influence that contributes to gallstone formation. The aim of this study was to assess the association between diet and GD. A nested case-control study based on a previous representative screening of asymptomatic subjects living in Rosario, Argentina, was carried out. Participants underwent a personal interview. Food and nutrient intake were estimated by applying a food-frequency questionnaire, a food photography atlas, and software for food composition. Logistic regression analysis was used to estimate Odds Ratios (OR) and 95% confidence intervals, adjusted by potential confounders. A total of 120 patients, 51 cases and 69 controls, were studied. Statistically significant differences in average daily energy intake were found between cases and controls (p = 0.002). Total fats, chicken with skin, sausages, and cold cuts intakes were higher in the cases group. However, the control group was characterized by a statistically significant higher consumption of vegetables, fresh fruits, nuts, chicken without skin, and skimmed dairy products. Multiple logistic regression showed that GD risk diminished with red and yellow vegetables (OR = 0.037; p = 0,0004) and nuts consumption (OR = 0.201; p = 0.019). Instead, GD risk increases with total fats (OR = 7.959; ρ = 0.0205), fatty cattle meat (OR = 18.163; p = 0.0063), and chicken with skin consumption (OR: 10.595; p = 0.0050). Phosphorus consumption decreases GD risk (OR = 0.055; p = 0.0035). A number of meals also acted as a protective factor. Also, caloric intake was a risk factor. Each 100 kilocalories daily consumed; the risk increases by 12%.

Liver Function-Related Indicators and Risk of Gallstone Diseases-A Multicenter Study and a Systematic Review and Meta-Analysis.

Purpose of the study: We aim to examine the association between liver function-related indicators and gallstone disease (GSD) risk. Study design: The subjects who participated in the China Multicenter Physical Examination Cohort (CMPEC) were enrolled. Relative odds ratios (ORs) with 95% CIs and standardized mean differences (SMDs) were applied to investigate the effect of liver function-related indicators and GSD risk. Moreover, a systematic review and meta-analysis were conducted until July 2021. Additionally, the results in the CMPEC and the systematic review and meta-analysis were combined by meta-analysis. Finally, the results were validated by a cohort study of the UK Biobank (UKB). Results and conclusions: Totally, 369,931 subjects in CMPEC were included in the study. A total of 28 publications were incorporated into the systematic review and meta-analysis. The pooled analysis suggested that aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein (TP), and low albumin (ALB) were positively associated with the risk of GSD. Meanwhile, GSD present to have higher AST, ALT, gamma-glutamyl transferase (GGT), total bilirubin (TBil), globulin (G), and ALP levels and relatively lower TP and ALB levels than the healthy participants. These results were consistent when stratified by the study design, geographic background, and study quality. Only the association between ALP and GSD risk was validated in the UKB cohort. This study suggests liver function indicators were associated with GSD risk. The results may provide the basis for exploring the etiology of GSD and may help clinicians identify high-risk subjects. Trial Registration: PROSPERO (CRD42020179076).

Protein Phosphatase 1 Regulatory Subunit 3 Beta rs4240624 Genotype Is Associated With Gallstones and With Significant Changes in Bile Lipidome

Gallstone disease (GSD) associates with significant morbidity and mortality. Decreased secretion of bile acids has been suggested as a driving factor for GSD. Recently, we linked the protein phosphatase 1 regulatory subunit 3 beta (PPP1R3B) rs4240624 genotype to decreased bile acid levels in bile. In this study, we investigated whether these individuals had an increased risk for GSD as well as the differences in the lipid composition of the gallbladder bile of these individuals compared to controls and patients with GSD. Bile acids, cholesterol, and phospholipid levels in gallbladder bile samples were enzymatically measured in 46 patients (34 female, age 45.7 ± 9.8 years, BMI 41.3 ± 4.4 kg/m2) who underwent elective laparoscopic Roux-en-Y gastric bypass. The lipidome of gallbladder bile was analyzed using high-performance liquid chromatography-mass spectrometry. Gallstone status was evaluated using abdominal ultrasonography before the surgery. The G allele of PPP1R3B rs4240624 was significantly associated with GSD in patients with obesity. We validated this association in the UK Biobank. Bile lipidomics demonstrated that 13 of the 17 minor lipid classes measured were higher in individuals with the G allele. The concentrations of bile acids, cholesterol, and phospholipids, as well as the cholesterol saturation index, were lower in patients with GSD than in those without gallstones. GSD had an effect similar to that of PPP1R3B genotype on minor lipids. The PPP1R3B rs4240624 genotype is associated with gallstones and with changes in gallbladder bile similar to those observed in patients with gallstones, suggesting that the PPP1R3B genotype contributes to the risk of gallstones by altering the bile lipidome.