Association of Differential Metabolites With Small Intestinal Microflora and Maternal Outcomes in Subclinical Hypothyroidism During Pregnancy

ObjectiveTo investigate the association of differential metabolites with small intestinal microflora and maternal outcomes in subclinical hypothyroidism (SCH) during pregnancy.MethodsThe plasma of pregnant women in the SCH group and control group was analyzed by liquid chromatography-mass spectrometry (LC-MS), obtaining differential metabolites. Then, methane and hydrogen breath tests were performed in both groups, and basic clinical data and maternal outcome information were collected. Finally, differential metabolites were analyzed for small intestinal bacterial overgrowth (SIBO) and pregnancy outcomes using Spearman correlation analysis.Results(1) Multivariate statistics: There were 564 different metabolites in positive ion mode and 226 different metabolites in negative ion mode. (2) The positive rate of the methane hydrogen breath test in the SCH group was higher than that in the control group (p<0.05). (3) KEGG pathway analysis revealed that differential metabolites were mainly involved in bile secretion, cholesterol metabolism, and other pathways. (4) Serum cholesterol (TC) and triglyceride (TG) levels and hypertensive disorder complicating pregnancy (HDCP) were higher in the SCH group (p<0.05), and newborn birth weight (BW) was lower than that in the control group (p<0.05). (5) SIBO was negatively correlated with glycocholic acid and BW, and positively correlated with TC. Glycocholic acid was negatively correlated with TG but positively correlated with BW. TG was positively correlated with HDCP.ConclusionDifferential metabolites in the SCH group during pregnancy were disordered with small intestinal bacteria, which may affect pregnancy outcomes, and bile acids and cholesterol may be potential biomarkers for studying their mechanism of action.

The effect of testosterone on the bile acid and bile lipid composition in rats

The study of sexual differences in the regulation of exocrine liver function is one of the topical areas in hepatology. After all, the liver serves as a mediator in a number of systemic effects of sex hormones on the body and is a key organ of their metabolism. In particular, the correlation between the concentration of steroid hormones can determine the direction of physiological processes and their possible distortions. Methods: physiological, biochemical, methods of mathematical statistics. Cholesecretion increased in female rats under the influence of testosterone. Testosterone raised the concentration of taurocholic acid and at the end of the acute experiment the level of taurohenodeoxycholic and taurodeoxycholic acids significantly increased. By comparison, the content of glycocholates decreased significantly immediately after the administration of the hormone but at the end of the experiment, the content of glycocholic acid increased significantly. The level of free bile acids increased under the testosterone. Testosterone affected the bile lipid composition, in particular, it raised the concentrations of phospholipids, cholesterol and its ethers, while the content of free fatty acids decreased under the studied hormone. Testosterone when administered intraperitoneally to female rats significantly affects the concentration of conjugated and free cholate, which may indicate its involvement in metabolic transformations and transport of bile acids to the primary bile ducts. The studied hormone raised the concentration of phospholipids, cholesterol and its ethers, but reduced the content of free fatty acids in the liver secretion of the studied animals.

Studies on Novel Diagnostic and Predictive Biomarkers of Intrahepatic Cholestasis of Pregnancy Through Metabolomics and Proteomics

BackgroundIntrahepatic cholestasis of pregnancy (ICP) usually occurs in the third trimester and is associated with increased risks in fetal complications. Currently, the exact mechanism of this disease is unknown. The purpose of this study was to develop potential biomarkers for the diagnosis and prediction of ICP.MethodsWe enrolled 40 pregnant women diagnosed with ICP and 40 healthy pregnant controls. The number of placental samples and serum samples between the two groups was 10 and 40 respectively. Ultra-performance liquid chromatography tandem high-resolution mass spectrometry was used to analyze placental metabolomics. Then, we verified the differentially expressed proteins and metabolites, both placental and blood serum, in the first, second, and third trimesters.ResultsMetabolomic analysis of placental tissue revealed that fatty acid metabolism and primary bile acid biosynthesis were enriched. In the integrated proteomic and metabolomic analysis of placental tissue, peroxisomal acyl-CoA oxidase 1 (ACOX1), L-palmitoylcarnitine, and glycocholic acid were found to be three potential biomarkers. In a follow–up analysis, expression levels of both placental and serum ACOX1, L-palmitoylcarnitine, and glycocholic acid in both placenta and serum were found to be significantly higher in third-trimester ICP patients; the areas under the ROC curves were 0.823, 0.896, and 0.985, respectively. Expression levels of serum ACOX1, L-palmitoylcarnitine, and glycocholic acid were also significantly higher in first- and second-trimester ICP patients; the areas under the ROC curves were 0.726, 0.657, and 0.686 in the first trimester and 0.718, 0.727, and 0.670 in the second trimester, respectively. Together, levels of the three aforementioned biomarkers increased the value for diagnosing and predicting ICP (AUC: 0.993 for the third, 0.891 for the second, and 0.932 for the first trimesters).ConclusionsL-palmitoylcarnitine, ACOX1, and glycocholic acid levels taken together may serve as a new biomarker set for the diagnosis and prediction of ICP.

Value of Serum Glycocholic Acid and Total Bile Acids in Predicting Maternal and Perinatal Outcomes in Intrahepatic Cholestasis of Pregnancy

Objective. To see whether serum glycocholic acid (CG) and total bile acids (TBA) can predict maternal and perinatal outcomes in pregnant women with intrahepatic cholestasis (ICP). Method. The observation group consisted of 80 women with ICP who were treated in our hospital, whereas the control group consisted of 50 ordinary women who were also treated at our hospital at the same time. The levels of CG and TBA in the two groups were determined independently, and the differences in poor perinatal outcomes were compared. Finally, the predictive diagnostic value of CG and TBA for poor perinatal outcomes in ICP mothers was displayed using the Spearman correlation between CG and TBA and Apgar. The maternal CG and TBA levels in the observation group were substantially higher than in the control group (P0.05). The observation group had more significant maternal-fetal discomfort, neonatal asphyxia, preterm birth, and perinatal death than the control group (P0.05). The risk of poor perinatal outcomes in ICP mothers rose when TBA and CG levels increased (P0.05). Apgar ratings were inversely associated with CG and TBA (r = −0.8251 and r = −0.5969, respectively, P0.05). The CG and TBA diagnostic AUCs for unfavorable perinatal outcomes in ICP mothers were (P0.05). Conclusion. CG and TBA have a high diagnostic value for ICP and may better predict and identify poor prenatal outcomes. It is suitable for clinical use.

Cold Stress Activates the UCP3 Pathway via Gut Microbiota in Piglet

BackgroundThe gut microbiota plays a key role in the host metabolic thermogenesis by activating uncoupling protein 1 (UCP1) and increasing the browning process of white adipose tissue, especially in a cold environment. However, the crosstalk between gut microbiota and pigs, which lack functional UCP1 making them susceptible to cold, has rarely been illustrated. We used male piglets as a model to evaluate the host response to cold stress via the gut microbiota. ResultsWe found that host thermogenesis and insulin resistance with increased serum metabolites, such as glycocholic acid (GCA), glycochenodeoxycholate (GCDCA), and chenodeoxycholate (CDCA), and altered cecal microbiota compositions and functions under cold stress. Using transcriptomics technology, we found that cytochrome P450, family 8, subfamily b, polypeptide 1 (CYP8B1), FXR, FFAR2, and FFAR3, which are related to bile acid and short-chain fatty acid metabolism, increased in the liver under cold stress. In addition, the fat lipolysis genes CLPS, PNLIPRP1, carnitine palmitoyltransferase 1B (CPT1B), and uncoupling protein 3 (UCP3) were significantly increased in the fat of piglets under cold stress. However, microbiota depletion via treatment with mixed antibiotics weakened the effect on the genes CYP8B1, FFAR2, FFAR3, and CPT1B genes, indicating that the gut microbiota plays important roles in the host thermogenesis. ConclusionsOur results demonstrate that the gut microbiota-blood-liver and fat axis may regulate thermogenesis during cold acclimation in piglets.

Serum Glycocholic Acid-to-Total Bile Acid Ratio Is Independently Associated with Nonalcoholic Fatty Liver Disease: A Retrospective Cross-Sectional Study

Introduction and Aims. Bile acids play an essential role in the progression of nonalcoholic fatty liver disease (NAFLD). This study was aimed at investigating the association of the serum glycocholic acid- (GCA-) to-total bile acid (TBA) ratio with NAFLD in the general population. Materials and Methods. A total of 6708 subjects (2859 cases with NAFLD and 3849 controls) were enrolled in the development cohort and additional 1568 subjects (784 cases with NAFLD and 784 controls) in an independent validation cohort. Demographic characteristics and biochemical data were compared between subjects with NAFLD and controls. Multivariate logistic regression analysis was performed to determine the association of the GCA-to-TBA ratio with NAFLD. A novel model incorporating the GCA-to-TBA ratio was developed for screening NAFLD from the general population. Results. The serum TBA and GCA levels were significantly higher in subjects with NAFLD than in those without NAFLD (2.8 (2.0-4.2) μmol/L vs. 2.5 (1.8-3.7) μmol/L and 1.30 (1.10-1.53) μg/mL vs. 1.28 (1.08-1.50) μg/mL, respectively, all p ≤ 0.01 ), whereas the serum GCA-to-TBA ratio was significantly lower in subjects with NAFLD than in subjects without NAFLD (0.44 (0.33-0.60) vs. 0.48 (0.36-0.64), p ≤ 0.01 ). Logistic regression analysis showed that the GCA-to-TBA ratio was independently associated with NAFLD after adjustment for confounding factors (odds ratio: 0.81, 95% confidence interval (CI): 0.71-0.92, p ≤ 0.01 ). The area under the receiver operating characteristic curve of the novel developed GCA-to-TBA ratio score model in discriminating NAFLD was 0.84 (95% CI: 0.83-0.85) in the development cohort and was 0.91 (95% CI: 0.36-0.65) in the validation cohort. Conclusion. The serum GCA-to-TBA ratio is independently associated with NAFLD. A simple novel model incorporating the GCA-to-TBA ratio score has a good performance in discriminating NAFLD from the general population.