Published online Dec 7, 2020. doi: 10.3748/wjg.v26.i45.7153
Peer-review started: August 17, 2020
First decision: September 12, 2020
Revised: September 21, 2020
Accepted: October 13, 2020
Article in press: October 13, 2020
Published online: December 7, 2020
Bile acids (BAs) have attracted attention in irritable bowel syndrome with predominant diarrhea (IBS-D) because of the effects on gastrointestinal motility and secretion function of the intestine. Experiments in animals and healthy volunteers also indicated that hypersensitivity can be caused by BAs, which is a major patho-physiological abnormality in IBS-D. The metabolism of BAs in the intestine depends on the gut microbiota. Therefore, it could be hypothesized that BAs may be involved in the pathogenesis of IBS-D and the altered BA profile in the intestine may be associated with microbiota.
Although a few studies have portrayed the composition of fecal BAs in IBS-D patients, the data in Chinese IBS-D patients are still sparse. Besides, few studies have explored the correlations between the gut flora and BAs in IBS-D patients. The main topics of this study included identifying the correlations of BAs with clinical features containing rectoanal sensory parameters of IBS-D patients, and exploring the correlations between the composition of fecal BAs and the gut microbiome. The findings may add insight to the pathogenesis of IBS-D, and provide evidence for regulating intestinal BAs to treat IBS-D.
The present study aimed to evaluate the correlations of BAs with clinical features of IBS-D patients and to explore whether the composition of fecal BAs was associated with the gut microbiome in IBS-D patients.
Subjects underwent clinical and psychological assessments, including IBS symptom severity system, the grade of Bristol stool form scale and defecation frequency per day in the preceding 2 wk, hospital anxiety and depression scale, and visceral sensitivity index, along with visceral sensitivity testing with a high-resolution manometry system. Fecal BAs were measured by ultraperformance liquid chromatography coupled to tandem mass spectrometry. The gut microbiota was analyzed using 16S rRNA gene sequencing. Relationships between fecal BAs and clinical characteristics as well as gut microbiota were explored.
Cholic acid, chenodeoxycholic acid (CDCA), and their conjugated BAs were significantly increased, while lithocholic acid (LCA) and ursodeoxycholic acid were significantly decreased and deoxycholic acid (DCA) tended to decrease in IBS-D patients. Defecation frequency was positively associated with primary BAs and inversely associated with DCA and LCA in IBS-D patients. The first sensation threshold was negatively correlated, and the defecating sensation threshold tended to be negatively correlated with CDCA in IBS-D patients. Furthermore, several genera were significantly reduced in IBS-D patients compared with HCs and exhibited a negative correlation with primary BAs and a positive correlation with secondary BAs, especially the genera in the Ruminococcaceae family.
This study presented evidence that the composition of the fecal BA pool was characterized by increased primary BAs and decreased secondary BAs in IBS-D, which was associated with diarrhea and visceral hypersensitivity in IBS-D. The dysmetabolism of BAs in IBS-D might be ascribed to gut dysbiosis especially the reduction of Ruminococcaceae.
In the future, careful evaluation of the usual dietary habit of subjects is required, and diet needs to be standardized during the study period. Large multicenter studies are also necessary to verify the conclusions drawn in this study. Notably, BA sequestrant may contribute to the studies on the involvement of BAs in IBS-D pathophysiology as well as the association between BAs and microbiota.