Gut Microbiome

Abstract

Biliary atresia (BA) is a fibro-obliterative condition of the biliary tree, presenting in infancy. The bilioenteric conduit formed at Kasai portoenterostomy (KPE), achieves restoration of bile flow in approximately 60% of infants. Even if the operation is successful, cirrhosis and its associated complications are, however, common. BA remains the leading cause for liver transplantation (LT) in children. Antibiotic, choleretic, and steroid therapy post-KPE have not convincingly reduced LT rates. Advances in molecular technology have enabled characterisation of the encoded genes of the gut microbiota (gut microbiome). The gut microbiome plays an important role in host metabolism, nutrition, and immune function, with alterations in its diversity and/or composition, known as dysbiosis, being described in disease states, including liver disease. Liver-gut microbiome exploration in adulthood largely focuses on nonalcoholic liver disease, cirrhosis (mainly alcohol- or viral-based aetiology) and cholestatic liver diseases (eg, primary sclerosing cholangitis), with microbial signatures correlating to disease severity. Investigation of the gut microbiota in BA had been limited to culture-based methodology, but molecular studies are emerging, and although in their infancy, highlight a potential pathogenic role for Enterobacteriaceae and Streptococcus, and a potential beneficial role for Bifidobacteria. Bacterial translocation, and the production of gut microbiome-derived metabolites, are key host-microbiome-mechanistic pathways in liver disease pathogenesis. Microbiome-targeted therapeutics for liver disease are in development, with faecal microbiota transplantation showing promise in cirrhosis. Could the gut microbiome be a novel modifiable risk factor in BA, reducing the need for LT?

Biliatresone and Biliary atresia – Disease modelling in C57BL/6J neonates

“…A toxic metabolic end product might arise due to a change in the metabolism depending on dysbiosis combined with disease promoting dietary intake. The human biliary and intestinal microbiota is a very complex network and part of recent discussion to be involved in progression of several diseases [114][115][116][117][118][119][120][121][122][123][124]. Retracing digestive potential of the microbiota it was observed that Rhizoctonia solani inoculated sugar beet roots take on a structure resembling biliatresone and that the bacterium Clostridium can break down a soybean iso avone into biliatresone [125][126][127].…”

A Predictive Model Based on the Gut Microbiota Improves the Diagnostic Effect in Patients With Cholangiocarcinoma

“…Among the differential phyla, Streptococcus is related to chronic alcoholic fatty liver disease, HBV-related acute-on-chronic liver failure, primary sclerosing cholangitis, etc. ( Jain et al., 2021 ; Kang et al., 2021 ; Tierney et al., 2021 ; Yao et al., 2021 ) In the meantime, the infection rate of Streptococcus is closely related to nutrient deficiency ( Guevara et al., 2020 ). Our result proposed the potential relationship between the CCA, MOJ, and intestinal microbiota and suggested the value and influence of intestinal microbiota on CCA early warning.…”

Malnutrition in Biliary Atresia: Assessment, Management, and Outcomes

“…( 20 ) Protein restriction is not recommended, even if advanced liver disease is present. Infants with BA may require up to 130% to 150% of recommended calories/energy for age to maintain or restore growth ( 16 ) but are often unable to take in this volume of calories orally as a result of organomegaly, ascites, delayed gastric emptying, and anorexia. Adequate calories for growth can be provided by increasing the caloric density of formula (or breast milk supplemented with formula/MCTs) from a baseline of 20 kcal/ounce up to 27 kcal/ounce.…”