Intestinal Microbiome Composition in Infants With Biliary Atresia (BA)

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.

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