Introduction
The densities of stem cells and their progenitors, and enteroendocrine cells are lower in IBS patients than healthy subjects.1,2 IBS patients also exhibit submucosal low-grade inflammation.3
Aims & Methods
This study investigated the possible mechanisms underlying the effects of FMT in IBS patients included in a previous study from our group that showed high and long-term efficacy. Ninety-three patients who participated in our previous study were investigated: placebo group (24 patients), the groups that received 30g (47patients) or 60g (22 patients) donor`s transplant. The patients underwent sigmoidoscopy with biopsies, provided faecal samples, and completed IBS-symptom severity score (IBS-SSS), Fatigue Assessment Scale (FAS), and IBS Quality of Life questionnaires at the baseline and at 1 month after FMT. Sections from the biopsy samples were immune-stained for Musahi-1 (marker for stem cells and in their early progeny), neurogenin 3 (marker for early endocrine cell progenitors), chromogranin A (general marker for enteroendocrine cells), serotonin, peptide YY (PYY), glucagon-like peptide 1, GLP-1, pancreatic polypeptide, somatostatin, CD 45 (common marker for immune cells), B lymphocytes, T lymphocytes. NK cells, monocytes, macrophages, myeloid cells, and mast cells. The cell densities were quantified by computerized image analysis. Faecal short chain fatty acids (SCFAs) were measured by gas chromatography, and faecal bacteria by 16S rRNA PCR DNA amplification covering variable regions V3–V9.
Results
The densities of Musashi-1, neurogenin 3, chromogranin A, serotonin, PYY, and GLP-1 expressing cells increased significantly following FMT in patients who received 30g, or 60g transplant, but not in the placebo group. The densities of Musashi-1, neurogenin 3, chromogranin A, serotonin, and GLP-1 expressing cells correlated inversely with IBS-SSS total scores (r=-0.4, P<0.0001; r= -0.2, P=0.007; r=- 0.3, P<0.0001; r=-0.2, P=004; r=-0.4, P<0.0001, respectively). The densities of Musashi-1, chromogranin A, and GLP-1 also correlated inversely with FAS total scores (r=-0.2, P=0.01; r= -0.2, P=0.002; r=- 0.3, P=0.0009, respectively). The density of PYY cells did not correlate with either IBS-SSS or FAS scores. The densities of total submucosal immune cells, and mast cells decreased significantly after FMT in patients treated with 30g, or 60g donor´s faeces, but were unchanged in the placebo group. The densities of these cells were correlated positively with IBS-SSS total scores (r=0.4, P<0.0001; r=0.5, P<0.0001, respectively), and the total immune cells correlated with FAS total scores (r=0.3, P=0.0002). The levels of butyric acid increased significantly following FMT in the 30g and 60g treated groups, but not in the placebo group. The faecal levels of butyric acid were inversely correlated with IBS-SSS (r=-04. P<0.0001), and FAS (r=-0.3, P<0.0001) total scores. Among the bacteria that their abundance increased significantly in IBS patients that received FMT were Alistipes, Faecalibacterium prausnitzii, Eubacterium biforme and Lactobacillus spp.
Conclusion
Stem cells, enteroendocrine progenitor, serotonin, and GLP-1cells, as well as low-grade inflammation appear to play a significant role in IBS symptom manifestation and that FMT effect most probably is due to restoring the abnormality in them. The present observations suggest potential new treatments for IBS such as transplantation of epithelial organoids containing stem cells, GLP-1 agonist, low-dose anti-inflammatory drugs, pharmacological drugs to control mast cell function3, and sodium butyrate.
References
1-El-Salhy M. Possible role of intestinal stem cells in the pathophysiology of irritable bowel syndrome. World J Gastroenterol 2020;26:1427-1438.
2-El-Salhy M, Hausken T, Gilja OH, et al. The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome. Expert Rev Gastroenterol Hepatol 2017;11:139-148.
3-Barbara G, Stanghellini V, De Giorgio R, et al. Functional gastrointestinal disorders and mast cells: implications for therapy. Neurogastroenterol Motil 2006;18:6-17.
Disclosure
Nothing to disclose
