Effects of faecal microbiota transplantation on the small intestinal mucosa in systemic sclerosis

Abstract

Objectives In systemic sclerosis (SSc), gastrointestinal tract (GIT) involvement is a major concern, with no disease-modifying and limited symptomatic therapies available. Faecal microbiota transplantation (FMT) represents a new therapeutic option for GIT-affliction in SSc, showing clinical promise in a recent controlled pilot trial. Here, we aim to investigate effects of FMT on duodenal biopsies collected from SSc patients by immunohistochemistry and transcriptome profiling. Methods We analysed duodenal biopsies obtained pre- (week 0) and post-intervention (weeks 2 and 16) from nine SSc patients receiving intestinal infusion of FMT (n = 5) or placebo (n = 4). The analysis included immunohistochemistry (IHC) with a selected immune function and fibrosis markers, and whole biopsy transcriptome profiling. Results In patients receiving FMT, the number of podoplanin and CD64-expressing cells in the mucosa were lower at week 2 compared to baseline. This decline in podoplanin- (r = 0.94) and CD64-positive (r = 0.89) cells correlated with improved patient-reported lower GIT symptoms. Whole biopsy transcriptome profiling from week 2 showed significant enrichment of pathways critical for cellular and endoplasmic reticulum stress responses, microvillus and secretory vesicles, vascular and sodium-dependent transport, and circadian rhythm. At week 16, we found enrichment of pathways mandatory for binding activity of immunoglobulin receptors, T-cell receptor complex, and chemokine receptor, as well as response to zinc-ions. We found that 25 genes, including Matrix metalloproteinase-1 were upregulated at both week 2 and week 16. Conclusion Combining selective IHC and unbiased gene expression analyses, this exploratory study highlights the potential for disease-relevant organ effects of FMT in SSc patients with GIT involvement.

The Clinical Significance of Serum Biomarkers of the Intestinal Barrier in Systemic Sclerosis: A Cross-Sectional Study

“…An improvement of the intestinal barrier by the mentioned interventions leads to a decrease in intestinal permeability and can be an effect of elevated expression of proteins of tight junction complexes in intestinal epithelial cells, stimulation of the proliferation of intestinal epithelial cells, and an increased secretion of mucins, which protect enterocytes from stressors [34][35][36]. Such attempts were also made in systemic sclerosis and were associated mainly with the improvement of gastrointestinal symptoms [37][38][39][40][41]. One study reported the immunomodulatory effect of a probiotic mixture manifested as a significant decrease in the proportion of Th17 cells compared with placebo [38].…”

“…One study reported the immunomodulatory effect of a probiotic mixture manifested as a significant decrease in the proportion of Th17 cells compared with placebo [38]. It is worth noting that the administration of probiotics as well as fecal microbiota transplantation exhibited an excellent safety profile, and the only noticed adverse events were mild and transient, i.e., diarrhea, bloating, and abdominal pain [37][38][39][40][41]. However, there is still little information available on the most appropriate probiotic strain composition and donor matching for fecal microbiota transplantation.…”