Category: Monday Poster Session
P1425 - Fecal Microbiota Transplantation Improves Microbiome Diversity and Liver Enzyme Profile in Primary Sclerosing Cholangitis
Monday, Oct 16
10:30 AM – 4:00 PM
Jessica R. Allegretti, MD, MPH1, Zain Kassam, MD, MPH2, Madeline Carrellas, BA3, Sonia Timberlake, PhD4, Ylaine Gerardin, PhD4, Daniel Pratt, MD5, Joshua Korzenik, MD3
1Brigham & Women's Hospital, Boston, MA; 2OpenBiome, Somerville, MA; 3Brigham & Women's Hospital, Boston, MA; 4Finch Therapeutics, Somerville, MA; 5Massachusetts General Hospital, Boston, MA
Introduction: Primary sclerosing cholangitis (PSC) is a progressive, chronic cholestatic liver disease with no effective medical therapies. Murine models suggest intestinal dysbiosis leads to hepatobiliary inflammation similar to PSC. Fecal microbiota transplantation (FMT) ameliorates dysbiosis and has been effective in 3 randomized controlled trials for ulcerative colitis (UC), which is associated with PSC. This study aimed to evaluate the safety, liver enzyme and microbiome profiles of PSC patients post FMT.
Methods: This open-label pilot study enrolled PSC patients with concurrent inflammatory bowel disease (IBD) and at least one: ALP, AST or ALT > 1.5X the upper limit of normal. All patients were off ursodeoxycholic acid. Participants had a single FMT by colonoscopy from a healthy, rationally selected donor. Liver profile and stool microbiome analysis was conducted at baseline and week 1, 4, 8, 12 and 26 post-FMT. The primary efficacy outcome was a decrease in ALP ≥50% from baseline post-FMT. Stool microbial profiles were determined by 16S rRNA sequencing.
Results: 10 patients have enrolled, and 6 have undergone FMT to date. Mean age was 36.1 years (SD 10.2) with 4 males (67%) and all had large duct PSC. 5 patients had concurrent UC (Mayo Score 0) and 1 Crohn’s colitis (HBI 0). Mean baseline ALP was 441.3 IU/L. Overall, there were no related adverse events. In terms of efficacy, 50% (3/6) of PSC patients had a ≥50% decrease ALP by week 26. Avg decrease in ALP among responders was 250 compared to 10 among non-responders by week 26 (p=0.001). Microbiome analysis revealed pre-FMT alpha diversity was significantly less than that of controls (p=0.00057) and diversity increased in all PSC patients at week 1 post-FMT (p=0.034) (Figure 1), and remained elevated in majority of patients. Pre-FMT patients exhibited variable taxonomic distributions at the class level; however, these distributions appeared more uniform post-FMT, (mean JSD decrease 0.18, n.s.) (Figure 2). Compared to controls, pre-FMT samples were enriched in Enterobacteriales (q=0.011) and Fusobacterium (p=0.01), previously reported as elevated in IBD and PSC, respectively. Enterobacteriales exhibited a non-significant decrease in all responders, but Fusobacterium remained elevated in all post-FMT samples compared to controls.
Discussion: To our knowledge, this is the first study to demonstrate that FMT from a rationally selected donor is safe, increases microbial diversity and may improve ALP among PSC patients.
Supported by Industry Grant: No
Disclosures: Does Disclose
Jessica Allegretti: Finch Therapeutics – Consultant, Grant/Research Support.
Zain Kassam: Finch Therapeutics – Consultant, Grant/Research Support, Stockholder/Ownership Interest (excluding diversified mutual funds). Openbiome – Employee.
Madeline Carrellas indicated no relevant financial relationships.
Sonia Timberlake: Finch Therapeutics – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Ylaine Gerardin: Finch Therapeutics – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Daniel Pratt indicated no relevant financial relationships.
Joshua Korzenik: Abbvie – Advisory Committee/Board Member, Grant/Research Support. colonaryconcepts – founder. Corrona – Consultant. Janssen – Consultant. Pfizer – Advisory Committee/Board Member, Grant/Research Support. Roche – Consultant.
Microbial community diversity as measured by the Shannon diversity index of 97% OTUs. PSC patients' pre-FMT diversity was significantly less than that of healthy stool donors ( p=0.00057) and increased in all patients post-FMT (p=0.034).
Microbial taxonomic composition at the class level in PSC patients and the FMT donor. Pre-FMT patients exhibited variable taxonomic compositions at the class level; these appeared more uniform post-FMT, when all patients became more similar to the donor (mean JSD decrease 0.18, n.s.). Compared to healthy controls, pre-FMT samples were enriched in the class Gammaproteobacteria (p=0.035, driven by Enterobacteriales members), which exhibited a (non-significant) decrease post-FMT in responders.
Citation: . FECAL MICROBIOTA TRANSPLANTATION IMPROVES MICROBIOME DIVERSITY AND LIVER ENZYME PROFILE IN PRIMARY SCLEROSING CHOLANGITIS. Program No. P1425. World Congress of Gastroenterology at ACG2017 Meeting Abstracts. Orlando, FL: American College of Gastroenterology.