BACKGROUND: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed at evaluating the safety, change in liver enzymes, microbiota, and metabolomic profiles in patients with PSC after FMT. METHODS: An open-label pilot study of patients with PSC with concurrent inflammatory bowel disease and alkaline phosphatase (ALP) > 1.5× the upper limit of normal was conducted. The patients underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis were conducted at baseline and weeks 1, 4, 8, 12, and 24 post-FMT. The primary outcome was safety, and the secondary outcome was a decrease in ALP levels ≥50% from baseline by week 24 post-FMT; stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed. RESULTS: Ten patients underwent FMT. Nine patients had ulcerative colitis, and 1 had Crohn's colitis. The mean baseline ALP level was 489 U/L. There were no related adverse events. Overall, 30% (3/10) experienced a ≥50% decrease in ALP levels. The diversity increased in all patients post-FMT, as early as week 1 (P < 0.01). Importantly, abundance of engrafter operational taxonomic units in patients post-FMT correlated with decreased ALP levels (P = 0.02). DISCUSSION: To our knowledge, this is the first study to demonstrate that FMT in PSC is safe. In addition, increases in bacterial diversity and engraftment may correlate with an improvement in ALP among patients with PSC.
BACKGROUND:Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed at evaluating the safety, change in liver enzymes, microbiota, and metabolomic profiles in patients with PSC after FMT. METHODS: An open-label pilot study of patients with PSC with concurrent inflammatory bowel disease and alkaline phosphatase (ALP) > 1.5× the upper limit of normal was conducted. The patients underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis were conducted at baseline and weeks 1, 4, 8, 12, and 24 post-FMT. The primary outcome was safety, and the secondary outcome was a decrease in ALP levels ≥50% from baseline by week 24 post-FMT; stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed. RESULTS: Ten patients underwent FMT. Nine patients had ulcerative colitis, and 1 had Crohn's colitis. The mean baseline ALP level was 489 U/L. There were no related adverse events. Overall, 30% (3/10) experienced a ≥50% decrease in ALP levels. The diversity increased in all patients post-FMT, as early as week 1 (P < 0.01). Importantly, abundance of engrafter operational taxonomic units in patients post-FMT correlated with decreased ALP levels (P = 0.02). DISCUSSION: To our knowledge, this is the first study to demonstrate that FMT in PSC is safe. In addition, increases in bacterial diversity and engraftment may correlate with an improvement in ALP among patients with PSC.
Authors: Benjamin H Mullish; Mohammed Nabil Quraishi; Jonathan P Segal; Gianluca Ianiro; Tariq H Iqbal Journal: Frontline Gastroenterol Date: 2020-02-04
Authors: Aldo J Montano-Loza; Jessica R Allegretti; Angela Cheung; Maryam Ebadi; David Jones; Nanda Kerkar; Cynthia Levy; Sumera Rizvi; John M Vierling; Fernando Alvarez; Wayne Bai; Susan Gilmour; Aliya Gulamhusein; Orlee Guttman; Bettina E Hansen; Sonya MacParland; Andrew Mason; Fernanda Onofrio; Pere Santamaria; Ashley Stueck; Mark Swain; Catherine Vincent; Amanda Ricciuto; Gideon Hirschfield Journal: Can Liver J Date: 2021-11-11
Authors: Martin Kummen; Louise B Thingholm; Malte C Rühlemann; Kristian Holm; Simen H Hansen; Lucas Moitinho-Silva; Timur Liwinski; Roman Zenouzi; Christopher Storm-Larsen; Øyvind Midttun; Adrian McCann; Per M Ueland; Marte L Høivik; Mette Vesterhus; Marius Trøseid; Matthias Laudes; Wolfgang Lieb; Tom H Karlsen; Corinna Bang; Christoph Schramm; Andre Franke; Johannes R Hov Journal: Gastroenterology Date: 2020-12-31 Impact factor: 22.682