Fecal microbiota transplantation in systemic sclerosis: A double-blind, placebo-controlled randomized pilot trial

• Published in: PloS one Vol. 15; no. 5; p. e0232739
• Main Authors: Fretheim, Håvard, Chung, Brian K, Didriksen, Henriette, Bækkevold, Espen S, Midtvedt, Øyvind, Brunborg, Cathrine, Holm, Kristian, Valeur, Jørgen, Tennøe, Anders Heiervang, Garen, Torhild, Midtvedt, Tore, Trøseid, Marius, Zarè, Hasse, Lund, May Brit, Hov, Johannes R, Lundin, Knut E A, Molberg, Øyvind, Hoffmann-Vold, Anna-Maria
• Format: Journal Article
• Language: English; Norwegian
• Published: United States Public Library of Science 21.05.2020; PLOS; Public Library of Science (PLoS)
• Subjects: Abundance; Bacteria; Biology and Life Sciences; Care and treatment; Clinical medicine; Clinical trials; Coatings; Complications; Diarrhea; Digestive system; Digestive tract; Disease; Double-blind studies; Dysbacteriosis; Engineering and Technology; Fecal incontinence; Fecal microflora; Feces; Gastroenterology; Gastroesophageal reflux; Hospitals; Immunoglobulin A; Immunoglobulin M; Internal medicine; Intestinal microflora; Intestine; Medicin och hälsovetenskap; Medicine; Medicine and Health Sciences; Microbiota; Microbiota (Symbiotic organisms); Motility; Patients; Physical Sciences; Randomization; Relative abundance; Research and Analysis Methods; Rheumatology; rRNA 16S; Safety; Scleroderma; Scleroderma (Disease); Side effects; Signs and symptoms; Systemic scleroderma; Systemic sclerosis; Testing; Transplantation; Norway; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0232739

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. 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. 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. 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.