Comprehensive Analysis of Gut Microbiota and Fecal Bile Acid Profiles in Children With Biliary Atresia.
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ABSTRACT: Background
Biliary atresia (BA) is the most common cholestatic liver disease in neonates. Herein, we aimed at characterizing the gut microbiota and fecal bile acid profiles of BA patients, defining the correlations between them, and evaluating the relationship between the clinical pathogenesis and changes in the gut microbiota and bile acid profiles.Methods
A total of 84 fecal samples from BA patients (n = 46) and matched healthy controls (HCs, n = 38) were subjected to sequencing by 16S rRNA gene amplification, and fecal bile acid were analyzed by targeted metabolomics.Findings
Compared with the controls, a structural separation of the intestinal flora of BA patients was uncovered, which was accompanied by changes in the composition of fecal bile acids. In the BA group, Actinobacillus, Monoglobus, and Agathobacter were enriched in patients without cholangitis (p < 0.05). Selenomonadaceae and Megamonas were more abundant in patients without recurrent cholangitis episodes (p < 0.05), while Lachnospiraceae and Ruminococcaceae were enriched in patients with multiple recurrences of cholangitis (p < 0.05). Postoperative jaundice clearance was associated with Campylobacter and Rikenellaceae (p < 0.05), and tauroursodeoxycholic acid was associated with jaundice clearance (p < 0.001).Conclusion
BA patients are characterized by different compositions of gut microbiota and bile acids, and their interaction is involved in the process of liver damage in BA, which may be closely related to the occurrence of postoperative cholangitis and jaundice clearance.
SUBMITTER: Yang T
PROVIDER: S-EPMC9247268 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC8502819 | biostudies-literature
Project description:Background and aimsBiliary atresia (BA) is an idiopathic neonatal cholestasis and is the most common indication in pediatric liver transplantation (LT). Previous studies have suggested that the gut microbiota (GM) in BA is disordered. However, the effect of LT on gut dysbiosis in patients with BA has not yet been elucidated.MethodsPatients with BA (n = 16) and healthy controls (n = 10) were recruited. In the early life of children with BA, Kasai surgery is a typical procedure for restoring bile flow. According to whether BA patients had previously undergone Kasai surgery, we divided the post-LT patients into the with-Kasai group (n = 8) and non-Kasai group (n = 8). Fecal samples were collected in both the BA and the control group; among BA patients, samples were obtained again 6 months after LT. A total of 40 fecal samples were collected, of which 16 were pre-LT, 14 were post-LT (8 were with-Kasai, 6 were non-Kasai), and 10 were from the control group. Metagenomic sequencing was performed to evaluate the GM.ResultsThe Kruskal-Wallis test showed a statistically significant difference in the number of genes between the pre-LT and the control group, the pre-LT and the post-LT group (P < 0.05), but no statistical difference between the post-LT and the control group. Principal coordinate analysis also showed that the microbiome structure was similar between the post-LT and control group (P > 0.05). Analysis of the GM composition showed a significant decrease in Serratia, Enterobacter, Morganella, Skunalikevirus, and Phifllikevirus while short chain fatty acid (SCFA)-producing bacteria such as Roseburia, Blautia, Clostridium, Akkermansia, and Ruminococcus were increased after LT (linear discriminant analysis > 2, P < 0.05). However, they still did not reach the normal control level. Concerning functional profiles, lipopolysaccharide metabolism, multidrug resistance, polyamine biosynthesis, GABA biosynthesis, and EHEC/EPEC pathogenicity signature were more enriched in the post-LT group compared with the control group. Prior Kasai surgery had a specific influence on the postoperative GM.ConclusionLT partly improved the GM in patients with BA, which provided new insight into understanding the role of LT in BA.
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Project description:Newborn Balb/c mice were injected intraperitoneally with 1.5x10^6 fluorescent-forming units (ffu) of type- A Rhesus Rotavirus (RRV) or 0.9% normal saline (NS; control) within 24 hours of birth to induce experimental model of biliary atresia. Extrahepatic bile ducts including gallbladder were microdissected en bloc at 3, 7 and 14 days after RRV or saline injections. GeneChipM-BM-. Mouse Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was differently regulated after RRV challenge compared to normal saline controls. Gene expression profiling: Each experimental conditon contains 3 sets of samples. Each sample consists of two to six extrahepatic bile ducts pooled prior to isolation of total RNA to ensure generation of adequate mRNA to perform quantitative experiments.
2013-06-01 | E-GEOD-46967 | biostudies-arrayexpress
Project description:BackgroundAssociations between colorectal cancer and microbiota have been identified. Archived fecal samples might be valuable sample sources for investigating causality in carcinogenesis and biomarkers discovery due to the potential of performing longitudinal studies. However, the quality, quantity and stability of the gut microbiota in these fecal samples must be assessed prior to such studies. We evaluated i) cross-contamination during analysis for fecal blood and ii) evaporation in stored perforated fecal immunochemical tests (iFOBT) samples, iii) temperature stability as well as iv) comparison of the gut microbiota diversity and composition in archived, iFOBT and fresh fecal samples in order to assess feasibility of large scale microbiota studies.MethodsThe microbiota profiles were obtained by sequencing the V3-V4 region of 16S rDNA gene.ResultsThe iFOBT does not introduce any cross-sample contamination detectable by qPCR. Neither could we detect evaporation during freeze-thaw cycle of perforated iFOBT samples. Our results confirm room temperature stability of the gut microbiome. Diverse microbial profiles were achieved in 100% of fresh, 81% of long-term archived and 96% of iFOBT samples. Microbial diversity and composition were comparable between fresh and iFOBT samples, however, diversity differed significantly between long-term archived, fresh and iFOBT samples.ConclusionOur data showed that it is feasible to exploit archived fecal sample sets originally collected for testing of fecal blood. The advantages of using these sample sets for microbial biomarker discovery and longitudinal observational studies are the availability of high-quality diagnostic and follow-up data. However, care must be taken when microbiota are profiled in long-term archived fecal samples.
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2013-06-01 | GSE46967 | GEO