Intestinal Microbiome Composition in Infants With Biliary Atresia (BA)

A prospective observational study in infants with biliary atresia and controls to determine whether the composition of the intestinal microbiome is specific for biliary atresia will be conducted.

The hypothesis of the study is "infants with biliary atresia have a unique microbiome signature at the time of diagnosis and changes in population dynamics occur during disease progression". The microbiome will be determined at diagnosis and at well-defined time points during the natural history of the disease.

Biliary atresia, the most common cause of neonatal cholestasis, results from a fibrosing and inflammatory obstruction of extrahepatic bile ducts of unknown etiology. Infants with neonatal cholestasis will be enrolled at the time of diagnosis. Those that undergo exploratory laparotomy and are diagnosed with biliary atresia will form the "biliary atresia".

The development of the normal bacterial flora is a dynamic process that varies in early postnatal ages and may be influenced by disease states. To control for age differences, the composition of the microbiome in subjects with other causes of neonatal liver diseases (non-biliary atresia or disease-controls) and age-matched healthy subjects (normal controls) will be determined.

Subjects with biliary atresia will be enrolled at diagnosis, at which time a stool sample and a 2 mL blood sample will be obtained. Thereafter, a stool sample will be obtained at 3±1 months after hepatoportoenterostomy (HPE) and at 24±6 months of age. A stool sample and a 2 ml blood sample will also be obtained if/when subjects are admitted to the hospital for an evaluation and treatment of presumed infection (example: ascending cholangitis) and at the time of liver transplantation.

Similar samples will also be obtained from healthy subjects (normal controls) and patients diagnosed with other cholestatic syndromes (non-biliary atresia or disease-controls) at ages that match those of subjects with biliary atresia. Samples will be used for bacterial DNA isolation, which will be used for bacterial and mammalian gene sequencing using next-generation sequencing methods, followed by statistical analysis to identify unique microbiome compositions or alterations that are associated with particular disease (biliary atresia or non-BA controls) or clinical outcomes including response to HPE, ascending cholangitis and progression of liver disease.

Eligibility Criteria:
Inclusion Criteria:

1. Age:

   -Birth to 5 months
2. Disease state: Must meet either (a), (b), or (c) for eligibility.

   a) Biliary atresia:
   * Conjugated hyperbilirubinemia (serum direct bilirubin \> 1mg/dL) AND demonstration of obstruction of extra hepatic bile ducts by examination of histological sections of extra hepatic bile ducts

     b) Neonatal cholestasis secondary to other causes of liver disease:
   * Diagnosis of liver disease caused by syndromes of intrahepatic cholestasis with or without hyperbilirubinemia

     c) Normal controls:
   * No acute or chronic liver related illness
3. Signed informed consent/assent

Exclusion Criteria:

1. Evidence of multi-organ system failure (e.g. combined liver and kidney failure)
2. For subjects \< 5 months old, treatment with antibiotics prior to enrollment into study