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Bile Acid Changes Associated With Liver Fibrosis and Steatosis in the Mexican-American Population of South Texas.

ABSTRACT: Biomarkers to predict risk of liver fibrosis in subjects with nonalcoholic fatty liver disease, a common risk factor for hepatocellular carcinoma, would allow for early preventive interventions. We sought to characterize bile acid profiles associated with liver fibrosis in subjects from the community-based Cameron County Hispanic Cohort, a population in South Texas with high rates of nonalcoholic fatty liver disease, liver fibrosis and hepatocellular carcinoma. Plasma bile acid levels were measured in 390 subjects. These subjects were screened with liver elastography, detecting significant liver fibrosis in 58 subjects and steatosis in 186 subjects. Unsupervised clustering of the bile acid profiles revealed five clusters that differed by liver fibrosis, liver steatosis, liver injury, age and gender, identifying these parameters as major determinants of circulating bile acid changes. Total bile acid levels were significantly higher in subjects with fibrosis, with chenodeoxycholic acid displaying the greatest increase among individual bile acids. The primary conjugated bile acids, glycocholic and glycochenodeoxycholic acids, displayed the strongest association with fibrosis by logistic regression. High lithocholic acid levels were strongly associated with advanced fibrosis. In contrast, deoxycholic acid and total unconjugated secondary bile acids were positively associated with steatosis, whereas relative glycoursodeoxycholic acid abundance was negatively associated. Milk and yogurt intake notably contributed to fibrosis-associated bile acid changes. In addition, multiple families within the Firmicutes phylum, Prevotellaceae, and Bacteroides species in stool significantly correlated with fibrosis-associated and steatosis-associated bile acid parameters, suggesting that the gut microbiome contributes to bile acid changes in the context of liver disease. Conclusion: Circulating bile acid levels were markedly but differently changed in liver fibrosis and steatosis in a high-risk Mexican-American population.

SUBMITTER: Kwan SY

PROVIDER: S-EPMC7109342 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Bile Acid Changes Associated With Liver Fibrosis and Steatosis in the Mexican-American Population of South Texas.

Kwan Suet Ying SY Jiao Jingjing J Qi Jonathan J Wang Ying Y Wei Peng P McCormick Joseph B JB Fisher-Hoch Susan P SP Beretta Laura L

Hepatology communications 20200319 4

Biomarkers to predict risk of liver fibrosis in subjects with nonalcoholic fatty liver disease, a common risk factor for hepatocellular carcinoma, would allow for early preventive interventions. We sought to characterize bile acid profiles associated with liver fibrosis in subjects from the community-based Cameron County Hispanic Cohort, a population in South Texas with high rates of nonalcoholic fatty liver disease, liver fibrosis and hepatocellular carcinoma. Plasma bile acid levels were measu ...[more]

PMID: 32258950

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Project description:BackgroundThe purpose of this study was to determine physical activity (PA) preferences associated with increases in moderate-to-vigorous physical activity (MVPA) and decrease in sedentary time in Mexican American (MA) women participating in a Promotora (community health worker)-led intervention on the U.S.-Mexico border.MethodsEnlace ('to link' in Spanish) was a randomized clinical trial to increase PA in low-income, MA women living in South Texas on the U.S.-Mexico border. A total of 620 participants were recruited into the study. The primary outcome was increase in moderate to vigorous physical activity (MVPA) using the Actigraph GT3X 16 Mb accelerometer. A modified version of the Community Health Activities Model Program for Seniors Physical Activity (CHAMPS) instrument was used to predict MVPA. Adjusted and unadjusted logistic regression models predicted change in MVPA by change in CHAMPS activities. ANOVA analysis determined the variance explained in change in MVPA by change in time engaged in activity. Individual effect sizes were then calculated for significant activity type change on MVPA increase.ResultsThere were significant increases in all CHAMPS activities except aerobic machines and errand walking. An increase in leisure walking (O.R. = 2.76, p = .046), errand (O.R. = 3.53, p = .051), and brisk walking (O.R. = 4.74, p = .011), dance (O.R. = 8.22, p = .003), aerobics class (O.R. = 32.7, p = .001), and light housework (O.R. = 6.75, p = .000), were associated with a decrease in sedentary time. Significant effect sizes for MVPA were observed for jogging (1.2, p = .050), general exercise (1.6, p = .024), and other exercise not specified (2.6, p = .003). Significant effect sizes for sedentary time were detected for leisure time (.031, p = .036), errands (.017, p = .022), brisk walking (.022, p = .003), dance (.042, p = .005), and aerobics class (.013, p = .009).DiscussionParticipants who engaged in walking and aerobic activities through this intervention significantly increased their engagement in MVPA and decreased their sedentary time. These findings are novel, since preferences have not been examined in relation to MVPA or sedentary time in MA women.ConclusionPA preferences need to be considered when aiming to promote activities that reduce sedentary time and increase PA participation among marginalized groups, such as MA women.Trial registrationNCT02046343 .

Project description:Mexican Americans have a high prevalence of diabetes and burden of diabetes-related complications, highlighting the need for novel preventive strategies and noninvasive predictors of diabetes risk tailored to this population. Changes in the gut microbiome have the potential to predict diabetes. Here, we aimed to identify alterations in the gut microbiome associated with diabetes in the high-risk population of Mexican Americans in South Texas. Stool samples were collected from 216 subjects from the population-based Cameron County Hispanic Cohort. Among them, 75 had type 2 diabetes. Taxonomic and functional profiling of the stool samples were assessed by 16S and shotgun metagenomic sequencing, and the influence of genetic factors was explored. The gut microbiome of subjects with diabetes was enriched with proinflammatory Proteobacteria members (Enterobacteriaceae, Escherichia-Shigella) and depleted of butyrate-producing Clostridiales members (Faecalibacterium prausnitzii, Peptostreptococcaceae, and Clostridium sensu stricto 1). The accompanying metagenomic changes in subjects with diabetes suggested dysregulated amino acid metabolism, reduced galacturonate and glucuronate catabolism (correlating with Faecalibacterium prausnitzii abundance), and enriched heme biosynthesis (correlating with Enterobacteriaceae abundance). Polymorphism rs7129790 near MMP27 was strongly associated with high Proteobacteria abundance and was more frequent in this cohort and in individuals of Mexican ancestry than in Europeans. In conclusion, Mexican Americans in South Texas with diabetes display distinct gut microbiome and metagenomic signatures. These signatures may have utility in risk modeling and disease prevention in this high-risk population. IMPORTANCE The gut microbiome composition varies across ethnicities and geographical locations, yet studies on diabetes-associated microbiome changes specific to high-risk Mexican Americans are lacking. Here, we aimed to identify specific alterations associated with diabetes in this population, as well as host genetic factors that may explain increased disease susceptibility in this ethnic group. Using samples from a population-based cohort of Mexican Americans with a high prevalence of obesity and diabetes, we confirmed findings from studies on other ethnicities that suggested promotion of a chronic proinflammatory environment, loss of butyrate production, and compromised intestinal barrier integrity. High abundance of proinflammatory Proteobacteria was associated with a polymorphism that was more frequent in this cohort and in individuals of Mexican ancestry than in Europeans. Validation of microbiome-based risk models for diabetes should be evaluated in prospective cohort studies.

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Dataset Information

Bile Acid Changes Associated With Liver Fibrosis and Steatosis in the Mexican-American Population of South Texas.

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Bile Acid Changes Associated With Liver Fibrosis and Steatosis in the Mexican-American Population of South Texas.

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