Short chain fatty acids analysis at week 0, 4 and 16

Short chain fatty acids analysis at week 0, 4 and 16.(XLSX) pone.0232739.s004.xlsx (16K) GUID:?92EA7B2B-19C2-48CF-8B6A-278452371DC7 S5 File: Supplementary information about ACHIM. study visits (week 0, 2, 4, 8, 12 and 16).(PDF) pone.0232739.s007.pdf (15K) GUID:?002A16D8-45E4-43C5-B3AE-33824CE7F6A9 S2 Fig: Calprotectin levels. Individual level of fecal calprotectin (mg/kg) at week 0, week AIGF 4 and week 16. A = active treatment group patient. P = placebo group patient.(PDF) pone.0232739.s008.pdf (192K) GUID:?B45D76E4-9E5B-4A20-96C3-E9189893F76E S3 Fig: Beta diversity. Individual beta diversity at week 0 (V1), week 4 (V3) and week 16 (V6).(PDF) pone.0232739.s009.pdf (181K) GUID:?6F79DD0B-A280-42E2-BD89-55F7DD9B6375 Data Availability StatementAll relevant data are within the paper and its Supporting Information files. Abstract 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 moderate 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 moderate 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 Chitinase-IN-1 and/or fecal incontinence was observed in four of five patients in the FMT group (week 4 or/and 16) Chitinase-IN-1 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 usually associated with gastroduodenoscopy complications but reduces lower GI symptoms by possibly altering the gut microbiota in patients with SSc. Introduction Systemic sclerosis (SSc) is usually a complex, multi-organ disorder characterized by immune-mediated inflammation, progressive organ fibrosis and vascular pathology [1]. Severity and extent of GI involvement varies within the SSc population, but overall, more than 90% of patients report GI symptoms [2]. The most commonly reported findings are reduced esophagus motility, gastroesophageal reflux disease (GERD), reduced intestinal motility, small intestine malabsorption and fecal incontinence [3, 4]. The mechanisms behind the GI affection in SSc are not well comprehended, but appear multifactorial [5, 6]. Previous studies show that intestinal microbiota composition in SSc differs from healthy individuals [7, 8]. To date, effective treatment alternatives for SSc-related GI disease are lacking and mostly limited to providing partial symptom relief [9, 10]. Fecal microbiota transplantation (FMT) is getting increasing attention as a potential therapeutic intervention for several diseases showing a good safety profile and relevant clinical effects; but it has not been assessed in rheumatic diseases, including SSc [11, 12]. One of the main challenges in prior FMT studies was donor-dependent variation of the fecal bacteria which could be overcome by using a standardized bacterial culture across all FMTs [13C15]. Herein, we performed a first-in-man fecal microbiota transplantation (FMT) pilot study with commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in patients with SSc to determine safety, effects Chitinase-IN-1 on Chitinase-IN-1 GI symptoms and on fecal microbiota composition. Materials and methods Study design and participants This was a single center randomized double-blind placebo controlled pilot trial with active intervention by a standardized FMT culture over 16 weeks with six study visits conducted at Oslo University Hospital between January and May 2018 (See S1 Fig). Patients were eligible for the study if they were between 18 and 70 years old, fulfilled the 2013 American College of Rheumatology/European League against Rheumatisms SSc classification criteria [16], and had clinically apparent upper and lower GI involvement (defined below). Study participants were recruited from the Oslo University Hospital rheumatology outpatient clinic from August to December 2017. To decrease the heterogeneity of the.