Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: A Pilot Clinical Trial.

Autor:	Allegretti JR; Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Kassam Z; Finch Therapeutics Group, Somerville, Massachusetts, USA., Carrellas M; Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA., Mullish BH; Division of Integrative Systems Medicine and Digestive Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Marchesi JR; Division of Integrative Systems Medicine and Digestive Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Pechlivanis A; Division of Integrative Systems Medicine and Digestive Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Smith M; Finch Therapeutics Group, Somerville, Massachusetts, USA., Gerardin Y; Finch Therapeutics Group, Somerville, Massachusetts, USA., Timberlake S; Finch Therapeutics Group, Somerville, Massachusetts, USA., Pratt DS; Harvard Medical School, Boston, Massachusetts, USA.; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA., Korzenik JR; Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	The American journal of gastroenterology [Am J Gastroenterol] 2019 Jul; Vol. 114 (7), pp. 1071-1079.
DOI:	10.14309/ajg.0000000000000115
Abstrakt:	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.
Databáze:	MEDLINE
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