Maternal regulation of biliary disease in neonates via gut microbial metabolites

Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding butyrate to pregnant mice influences the newborn’s susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells.

Pregnancy Outcomes of Non-Visualization of The Foetal Gallbladder From A Chinese Tertiary Single Centre And Literature Review

Objection To explore the clinical features and prognosis of non-visualization of fetal gallbladder (NVFGB). Methods 65 cases diagnosed of NVFGB in the Peking University First Hospital was collected retrospectively from January, 2019 to December, 2020. Results 49 cases were successfully followed up. Among them, the gallbladder of 21 fetuses (42.9%) was visible later, either in the later pregnancy or after birth. In the rest 28 cases (57.1%), the gallbladders were not seen during the whole pregnancy. 11 of 28 fetuses (39.3%) with NVFGB were complicated with other structure anomaly. In the remaining 17 cases of isolated NVFGB (60.7%), one case was diagnosed of congenital biliary atresia, 3 cases of small gallbladder, 1 case of gallstone and one case of irregular size of gallbladder. There are 9 cases who underwent prenatal diagnosis, with 4 cases of abnormal result. Conclusion Prenatal ultrasound plays a role in the early recognize of abnormal gallbladder, which will improve the postnatal prognosis.

VEGFA rs3025039 and biliary atresia susceptibility in Chinese population: a systematic review and meta-analysis

BackgroundPrevious studies have suggested an association between vascular endothelial growth factor A (VEGFA) rs3025039 polymorphism and biliary atresia (BA). However, this conclusion is controversial and there is no published pooled evidence of this association.MethodsThis study was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews). A thorough search was performed on databases including PubMed, Embase, and Chinese Biomedical Database up to August 2020. This study included 846 cases of BA and 2821 controls concerning VEGFA rs3025039 polymorphism. We selected relevant studies based on the following inclusion criteria: (1) the study design was case–control and cohort and (2) the patients carried standard clinical diagnoses of BA, etc. The exclusion criteria were as follows: (1) patients with other related diseases, (2) lack of requisite information and (3) duplicate data. The OR (odd ratio) and the corresponding 95% CI (confidence interval) were calculated to estimate the association.ResultsThis study on VEGFA rs3025039 polymorphism in the Chinese population included 846 cases and 2821 controls. The results showed that there was no significant association between rs3025039 and susceptibility to BA under four genetic models. The results of the subgroup analysis were similar to the overall results.ConclusionsThis meta-analysis shows that rs3025039 was not associated with susceptibility to BA in the Chinese population. Further validation may entail additional research.PROSPERO registration numberCRD42020203812.