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.

p,p’-dichlorodiphenyldichloroethylene (p, p’-DDE) and β-hexachlorocyclohexane (β-HCH) were two predominant organochlorine pesticides (OCPs) metabolites in human body associated with disorders of fatty acid metabolism. However, the underlying mechanisms have not been fully clarified. In this study, adult male C57BL/6 mice were exposed to low dose of p, p’-DDE and β-HCH for 8 wk. OCPs accumulation in organs, hepatic fatty acid composition, tricarboxylic acid cycle (TCA) metabolites and other metabolite profiles were analyzed. Expression levels of genes involved in hepatic lipogenesis and β-oxidation were measured. Mitochondrial function was evaluated in HepG2 cells exposed to OCPs. High accumulation of p, p’-DDE and β-HCH was found in liver and damaged mitochondria was observed under electron microscopy. Expression of genes in fatty acid synthesis increased and that in mitochondrial fatty acid β-oxidation decreased in OCPs treatment groups. OCPs changed metabolite profiles in liver tissues, varied hepatic fatty acid compositions and levels of several TCA cycle metabolites. Furthermore, MitoTracker Green fluorescence, ATP levels, mitochondrial membrane potential and OCR decreased in HepG2 cells exposed to OCPs. In conclusion, chronic exposure to OCPs at doses equivalent to internal exposures in humans impaired mitochondrial function, decreased fatty acid β-oxidation and aggravated disorders of fatty acid metabolism.

Global prevalence of obesity has been increasing dramatically in all ages. Although traditional causes for obesity development have been studied widely, it is unclear whether environmental exposure of substances such as trace heavy metals affects obesity development among children and adolescents so far. Data from the National Health and Nutrition Examination Survey (1999-2011) were retrieved, and 6602 US children were analyzed in this study. Urinary level of nine trace heavy metals, including barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, and tungsten, was analyzed for their association with the prevalence of obesity among children aged 6-19 years. Multiple logistic regression was performed to assess the associations adjusted for age, race/ethnicity, gender, urinary creatinine, PIR, serum cotinine, and television, video game, and computer usage. A remarkable association was found between barium exposure (OR 1.43; 95% CI 1.09-1.88; P < 0.001) and obesity in children aged 6-19 years. Negative association was observed between cadmium (OR 0.46; 95% CI 0.33-0.64; P < 0.001), cobalt (OR 0.56; 95% CI: 0.41-0.76; P < 0.001), and lead (OR 0.57; 95% CI 0.41-0.78; P = 0.018), and obesity. All the negative associations were stronger in the 6-12 years group than in the 13-19 years group. The present study demonstrated that barium might increase the occurrence of obesity, but cadmium, cobalt, and lead caused weight loss among children. The results imply that trace heavy metals may represent critical risk factors for the development of obesity, especially in the area that the state of metal contamination is serious.