Gastrointestinal Microbiota in Primary Sclerosing Cholangitis and Biliary Atresia With Vancomycin

Overview

The goals of the proposed work are two fold: Firstly, to see if the antibiotic vancomycin may be used for the early treatment of Biliary Atresia (BA) and Primary Sclerosing Cholangitis (PSC). The investigators hope to learn what effect Vancomycin has on the bacteria that are present in stool, body fluid or intestinal tissue on someone who has BA and PSC and if so by what mechanism. Secondly, the investigators hope to learn to characterize human intestinal microbial communities (microbiome: the collection or collectivity of microorganisms) using molecular methods, examine the mechanisms of interaction between host and microbiome using genomic approaches, and determine how the microbiome both preserves local health and promotes pathology. The investigators will focus on primary sclerosing cholangitis, biliary atresia, as well as states of health. The composition of the associated microbiome will be assessed based on ribosomal DNA and RNA sequences, and attention will be given to richness (diversity), evenness (relative abundance), and variation with respect to time, person, and anatomic niche. Host response at the adjacent mucosal surface will be assessed based on genome-wide gene expression patterns.

As many as 55 subjects (35 with BA or PSC and 20 Controls) will be involved. We are also recruiting 20 adult patients with either BA, or PSC. The patients will be recruited from Lucile Children's Hospital, Stanford Medical Center, and Stanford Redwood City Campus such as patients with primary sclerosing cholangitis, biliary atresia or other intestinal disorders for whom upper or lower endoscopy is indicated for routine medical management. There may be some participants who are over 18 years of age although the vast majority will be under 18. Vancomycin therapy will be administered to the BA patients (4 weeks)and PSC patients. The PSC patient blood tests would now be done at various intervals: before starting the Vancomycin; every month until their Liver Function Tests are normalized; after their Liver Function Tests are normalized; before stopping the Vancomycin and after they are off the Vancomycin at month 1,3,6,12,and 24. Fecal samples will be taken. In addition, patients who will already be undergoing either upper or lower intestinal endoscopy for routine diagnostic or therapeutic purposes will be asked to agree to endoscopic mucosal brushings in addition to mucosal biopsies. Some will be patients with a diagnosis of primary sclerosing cholangitis, biliary atresia, or other intestinal disorders for whom upper or lower endoscopy is indicated for routine medical management. Others will have lower intestinal findings (polyps) or complaints (e.g. occult blood in stool), or upper intestinal findings (dyspepsia, reflux), and will be undergoing lower endoscopy (colonoscopy) or upper endoscopy for routine medical management. Up to 2 biopsies will be obtained from the gastric mucosa and of as many as 6 intestinal sites from each patient. In addition the following brushings will be taken: 2 from mid-esophagus, 2 from lesser curvature of the stomach, 2 from the second portion of the duodenum near the ampulla. 2 from the jejunum 5 cm from the Ligament of Trietz, and 2 from the ileum 10 cm from the ileocecal valve. We will also obtain brushing from the tongue. A sample of saliva will be taken. Fecal specimens will also be collected just prior to bowel preparation for endoscopy/colonoscopy. If the BA patient is already having a Kasai portoenterostomy, done to remove the diseased bile ducts, we would like to take a biopsy of the bile duct. If the patient has a liver biopsy clinically done we would like to keep a 2mm section of it. If the patient has an intraoperative cholangiogram to evaluate the bile ducts we will collect 2.5 cc. of bile fluid. With regards to the controls, who have other intestinal disorders and are also having clinical endoscopies done, we would request a midesophagus biopsy; a biopsy from the antrum and 2 biopsies from the 4th portion of the duodenum. Cell brushings will be taken from the following areas: 2 from mid-esophagus, 2 from lesser curvature of the stomach, 2 from the second portion of the duodenum near the ampulla. 2 from the jejunum 5 cm from the Ligament of Trietz, and 2 from the ileum 10 cm from the ileocecal valve. We will also obtain brushing from the tongue. A sample of saliva will be taken. If the patient is having a colonoscopy done as part of their clinical care we would request a biopsy from the ileum, cecum, and transverse descending rectum. We would also ask for a saliva sample. The blood tests would now be done at various intervals: before starting the Vancomycin; every month until their Liver Funtion Tests are normalized; after their Liver Function Tests are normalized; before stopping the Vancomycin and after they are off the Vancomycin at month 1,3,6,12 and 24.