Background Systemic sclerosis (SSc) is a progressive, multi organ, auto-immune disease marked by frequent and severe gastrointestinal (GI) afflictions and gut dysbiosis.
Objectives Determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in patients with SSc.
Methods The trial was a single-center, randomized, double-blind, placebo-controlled 16-week pilot of FMT by gastroduodenoscopy of ACHIM in SSc conducted at Oslo University Hospital. Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16. Safety was assessed by observation, interviews and standardized safety form. Efficacy on GI symptoms was measured using the UCLA GIT 2.0 score questionnaire. Patients were defined as responders if reported symptom improvement was equivalent to the UCLA GIT definition of “minimally clinically important difference”. Secondary and explorative endpoints included changes in relative abundance of total, immunoglobulin (Ig)A- and IgM-coated fecal bacteria measured by 16s rRNA sequencing; changes in modified Rodnan skin score, lung function, CRP, ESR, and patient and physician global. Descriptive statistics were applied for clinical endpoints and linear mixed models for microbial analysis.
Results Ten patients with limited cutaneous SSc randomized to ACHIM (n=5) or placebo (n=5) were included. All patients were female with clinical apparent GI symptoms, mean age of 62 years and mean time from diagnosis of 12 yrs. Two placebo controls experienced procedure-related serious adverse events; one developed laryngospasms at first gastroduodenoscopy necessitating study exclusion, one duodenal perforation at final gastroduodenoscopy. Improvement in total GIT score was reported by 3/5 FMT patients compared to 2/4 placebo controls at weeks 4 and 16 (Figure 1). FMT effects were most pronounced on lower GI symptoms, with improvement reported by 5/5 FMT patients with diarrhea, distention/bloating and/or fecal incontinence at baseline compared to 2/4 placebo controls (Figure). Clinical secondary endpoints showed no differences and other side effects (stomach discomfort, bloating and diarrhea) were mild and transient. Fecal microbiota diversity (observed number of operational taxonomic units) was increased after FMT compared to placebo treatment at week 16 (p<0.006). Moreover, abundant bacterial genera in ACHIM were present within the total, and IgA- and IgM-coated fecal bacteria at both week 4 and 16 in the FMT group (Figure 2) but not in the placebo controls.
Conclusion FMT of commercially-available ACHIM in patients with SSc appeared safe, effectively reduced lower GI symptoms, altered gut microbiota composition, richness and diversity and appeared to affect the mucosal immune system
Disclosure of Interests Anna-Maria Hoffmann-Vold Grant/research support from: Received research funding or other remuneration from Boehringer Ingelheim, GSK, and Actelion, Consultant for: Received consulting fees or other remuneration from Boehringer Ingelheim, GSK, and Actelion, Speakers bureau: Actelion and Boehringer Ingelheim, Håvard Fretheim Consultant for: Received consulting fees or other remuneration from GSK, and Actelion, Brian K Chung: None declared, Henriette Didriksen Consultant for: Received consulting fees or other remuneration from GSK, and Actelion, Espen S Bækkevold: None declared, Øyvind Midtvedt: None declared, Cathrine Brunborg: None declared, Torhild Garen: None declared, Tore Midtvedt Shareholder of: Owner of ACHIM, Johannes R Hov: None declared, Knut EA Lundin: None declared, Øyvind Molberg: None declared
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