Potential role of fecal microbiota from patients with slow transit constipation in the regulation of gastrointestinal motility

Xiaolong Ge,Hongkan Wang,Lizhi Xu,Weiming Zhu,Jianfeng Gong,Wei Zhao,Chao Ding,Jun Jiang,Minsheng Zhu,Ning Li,Ling Ni,Hongliang Tian

doi:10.1038/s41598-017-00612-y

Abstract

The gut microbiota is involved in various physiological functions, and disturbances in the host-microbiome have been proven to contribute to the dysfunction of gut; however, whether microbiota participates in the pathogenesis of constipation remains unclear. In this study, we extracted and analyzed microbiota in feces from constipated donors who had undergone effective therapy with fecal microbiota transplantation, transplanted microbiota into pseudo-germ-free mice, and measured gut motility. These mice presented with lower pellet frequency and water percentage, smaller pellet size, delayed gastrointestinal transit time, and weaker spontaneous contractions of colonic smooth muscle. To determine the mechanism underlying delayed gut motility, microbial metabolites were measured. Short chain fatty acids and secondary bile acids were decreased in mice receiving microbiota from constipated donors. Moreover, the compositional changes of gut microbiota in constipated patients were identified, including the operational taxonomic unit, and the species richness and α diversity were much greater than those in healthy volunteers. These findings suggest that alterations of the microbiome might affect gut motility via altered microbial-derived metabolites in the development of constipation, and the restoration of disturbed microbiota might improve the clinical phenotype. This study indicates that regulating the intestinal environment may be a novel therapy strategy for constipation.

Highlights

Chronic constipation is a functional bowel disorder with a high incidence worldwide, affecting 14% of adults and almost 36% of the elderly[1]
The microbiota analyses showed that the operational taxonomic unit (OTU) of constipated patients was greater than that of healthy donors (180.2 ± 13.6 vs 123.7 ± 3.2, respectively; p = 0.021), with increased species richness (Chao index, 186.3 ± 14.2 vs 143.3 ± 10.9, respectively; p = 0.082) and α diversity (Shannon index, 3.54 ± 0.06 vs 3.06 ± 0.06, respectively; p = 0.006)
The patient assessment of constipation symptoms questionnaire (PAC-SYM) and gastrointestinal quality-of-life index (GIQLI) scores were improved at 12 weeks after fecal microbiota transplantation (FMT)

Summary

Introduction

Chronic constipation is a functional bowel disorder with a high incidence worldwide, affecting 14% of adults and almost 36% of the elderly[1]. The abundance of methanogens (such as Methanobrevibacter) was increased in harder stools, a finding that was consistent with the elevated methane production in patients with chronic constipation, and methane was suggested to slow down gut motility[17]. These pathophysiological changes in constipated patients raise the reflections on whether striking changes in the fecal flora could be one cause of constipation. It was demonstrated that FMT was safe and effective for chronic constipation with clinical improvement and remission rates were 66.7% and 42.9% at our hospital[18] These studies on the relationship between microbiota and gut motility did not discuss whether striking changes in the fecal flora are the cause of constipation. Secondary BAs were proposed to directly act on ECs to synthetize 5-HT by elevating colonic TPH1 expression23. 5-HT was reported to induce the contraction of colonic myocytes due to the release of Ca2+ from the sarcoplasmic reticulum by activating 5-HT3 receptors and the inositol 1, 4, 5-trisphosphate pathway[24]

Methods

Results

Conclusion