Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome

• Published in: World journal of gastroenterology : WJG 2020-12, Vol.26 (45), p.7153-7172
• Main Authors: Wei, Wei, Wang, Hui-Fen, Zhang, Yu, Zhang, Yan-Li, Niu, Bing-Yu, Yao, Shu-Kun
• Format: Article
• Language: English
• Subjects: Bile Acids and Salts; Case Control Study; China; Diarrhea - diagnosis; Feces; Gastrointestinal Microbiome; Humans; Irritable Bowel Syndrome - diagnosis; Japan; RNA, Ribosomal, 16S
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v26.i45.7153

Bile acids (BAs) have attracted attention in the research of irritable bowel syndrome with predominant diarrhea (IBS-D) due to their ability to modulate bowel function and their tight connection with the gut microbiota. The composition of the fecal BA pool in IBS-D patients is reportedly different from that in healthy populations. We hypothesized that BAs may participate in the pathogenesis of IBS-D and the altered BA profile may be correlated with the gut microbiome. To investigate the role of BAs in the pathogenesis of IBS-D and the correlation between fecal BAs and gut microbiota. Fifty-five IBS-D patients diagnosed according to the Rome IV criteria and twenty-eight age-, sex-, and body mass index-matched healthy controls (HCs) were enrolled in this study at the gastroenterology department of China-Japan Friendship Hospital. First, clinical manifestations were assessed with standardized questionnaires, and visceral sensitivity was evaluated the rectal distension test using a high-resolution manometry system. Fecal primary BAs including cholic acid (CA) and chenodeoxycholic acid (CDCA), secondary BAs including deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) as well as the corresponding tauro- and glyco-BAs were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry. The gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between fecal BAs with clinical features and gut microbiota were explored. Fecal CA (IBS-D: 3037.66 [282.82, 6917.47] nmol/g, HC: 20.19 [5.03, 1304.28] nmol/g; < 0.001) and CDCA (IBS-D: 1721.86 [352.80, 2613.83] nmol/g, HC: 57.16 [13.76, 1639.92] nmol/g; < 0.001) were significantly increased, while LCA (IBS-D: 1621.65 [58.99, 2396.49] nmol/g, HC: 2339.24 [1737.09, 2782.40]; = 0.002] and UDCA (IBS-D: 8.92 [2.33, 23.93] nmol/g, HC: 17.21 [8.76, 33.48] nmol/g; = 0.025) were significantly decreased in IBS-D patients compared to HCs. Defecation frequency was positively associated with CA ( = 0.294, = 0.030) and CDCA ( = 0.290, = 0.032) and negatively associated with DCA ( = -0.332, = 0.013) and LCA ( = -0.326, = 0.015) in IBS-D patients. In total, 23 of 55 IBS-D patients and 15 of 28 HCs participated in the visceral sensitivity test. The first sensation threshold was negatively correlated with CDCA ( = -0.459, = 0.028) in IBS-D patients. Furthermore, the relative abundance of the family was significantly decreased in IBS-D patients ( < 0.001), and 12 genera w