Open AccessFecal microbiota transplantation in systemic sclerosis: A double-blind, placebo-controlled randomized pilot trial
Author(s) -
Håvard Fretheim,
Bryan Chung,
Henriette Didriksen,
Espen S. Bækkevold,
Øyvind Midtvedt,
Cathrine Brunborg,
Kristian Holm,
Jørgen Valeur,
Anders Heiervang Tennøe,
Torhild Garen,
Tore Midtvedt,
Marius Trøseid,
Hasse Khiabani Zaré,
May Brit Lund,
Johannes R. Hov,
Knut E.A. Lundin,
Øyvind Molberg,
AnnaMaria HoffmannVold
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0232739
Subject(s) - placebo , gastroenterology , medicine , bloating , clinical endpoint , diarrhea , dysbiosis , adverse effect , transplantation , immunology , randomized controlled trial , pathology , disease , alternative medicine
Objectives Systemic sclerosis (SSc) is an auto-immune, multi organ disease marked by severe gastrointestinal (GI) involvement and gut dysbiosis. Here, we aimed to determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in SSc. Methods Ten patients with SSc were randomized to ACHIM (n = 5) or placebo (n = 5) in a double-blind, placebo-controlled 16-week pilot. All patients had mild to severe upper and lower GI symptoms including diarrhea, distention/bloating and/or fecal incontinence at baseline. Gastroduodenoscopy transfer of ACHIM or placebo was performed at weeks 0 and 2. Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16. Secondary endpoints included changes in relative abundance of total, immunoglobulin (Ig) A- and IgM-coated fecal bacteria measured by 16s rRNA sequencing. Results ACHIM side effects were mild and transient. Two placebo controls experienced procedure-related serious adverse events; one developed laryngospasms at week 0 gastroduodenoscopy necessitating study exclusion whilst one encountered duodenal perforation during gastroduodenoscopy at the last study visit (week 16). Decreased bloating, diarrhea and/or fecal incontinence was observed in four of five patients in the FMT group (week 4 or/and 16) and in two of four in the placebo group (week 4 or 16). Relative abundance, richness and diversity of total and IgA-coated and IgM-coated bacteria fluctuated more after FMT, than after placebo. Conclusions FMT of commercially-available ACHIM is associated with gastroduodenoscopy complications but reduces lower GI symptoms by possibly altering the gut microbiota in patients with SSc.