Several studies on the role of HCA species in regulating glucose homeostasis have indicated their therapeutic value in human obesity and diabetes. There is a clear difference in the percentage of hyocholic acid (HCA) and its derivatives (also known as HCA species) in the total bile acid (BA) pool in the plasma between humans, rats and pigs. However, the role of gut microbiota in BA profiles of pigs remains unclear. We generated five germ-free pig models and six gnotobiotic pig models by fecal microbiota transplantation (FMT). A total of 46 BAs were detected in the jejunum, cecum, colon, and rectum chyme, 37 and 33 BAs were detected in bile, 33 BAs were detected in ileal chyme and liver, and 31 BAs were detected in serum. FMT increased the percentages of HCA species in total bile acids in the serum (79%), liver (78%), and bile (71%), but decreased the proportions of HCA species in the total BAs of the ileum (61%), cecum (47%), colon (51%), and rectum (57%) of pigs, as compared to GF piglets. FMT significantly induced the production of conjugated bile acids in the small intestine and increased the concentrations of free BAs in the large intestine of pigs (P < 0.01). FMT piglets had over 68-fold and 104-fold increases in conjugated BAs in the ileum compared to the germ-free piglets. FMT piglets had an expression pattern distinct from that of germ-free piglets for genes involved in bile acid receptors, synthesis, signaling, and transport. The gene expression levels of the rate-limiting enzyme CYP7A1 and the enzymes CH25H and BAAT involved in BA synthesis were significantly decreased in the liver of FMT piglets, and there was a significant reduction in the gene expression of FXR and TGR5 through the FGFR4/β-Klotho pathway that promotes the BA pool in the liver of piglets after FMT.

Background. The purpose of this research was to assess the relationship between the severity of diabetic retinopathy (DR) and indexes of left ventricle (LV) structure and function in type 2 diabetes mellitus (T2DM). Methods. Retrospective analysis of 790 patients with T2DM and preserved LV ejection fraction. Retinopathy stages were classified as no DR, early nonproliferative DR, moderate to severe nonproliferative DR, or proliferative DR. The electrocardiogram was used to assess myocardial conduction function. Echocardiography was used to evaluate myocardial structure and function. Results. Patients were divided into three groups based on the DR status: no DR group (NDR, n = 475 ), nonproliferative DR group (NPDR, n = 247 ), and proliferative DR group (PDR, n = 68 ). LV interventricular septal thickness (IVST) increased significantly with more severe retinopathy (NDR: 10.00 ± 1.09 ; NPDR: 10.42 ± 1.21 ; and PDR: 10.66 ± 1.58 ; P < 0.001). Multivariate logistic regression analysis showed that the significant correlation of IVST persisted between subjects with no retinopathy and proliferative DR (odds ratio = 1.35 , P = 0.026 ). Indices of myocardial conduction function were assessed by electrocardiogram differences among groups of retinopathy (all P < 0.001 ). In multiple-adjusted linear regression analyses, the increasing degree of retinopathy was closely correlated with heart rate ( β = 1.593 , P = 0.027 ), PR interval ( β = 4.666 , P = 0.001 ), and QTc interval ( β = 8.807 , P = 0.005 ). Conclusion. The proliferative DR was independently associated with worse cardiac structure and function by echocardiography. Furthermore, the severity of retinopathy significantly correlated with abnormalities of the electrocardiogram in patients with T2DM.