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

Abstract

BACKGROUND 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. AIM To investigate the role of BAs in the pathogenesis of IBS-D and the correlation between fecal BAs and gut microbiota. METHODS 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 via 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. RESULTS Fecal CA (IBS-D: 3037.66 [282.82, 6917.47] nmol/g, HC: 20.19 [5.03, 1304.28] nmol/g; P < 0.001) and CDCA (IBS-D: 1721.86 [352.80, 2613.83] nmol/g, HC: 57.16 [13.76, 1639.92] nmol/g; P < 0.001) were significantly increased, while LCA (IBS-D: 1621.65 [58.99, 2396.49] nmol/g, HC: 2339.24 [1737.09, 2782.40]; P = 0.002] and UDCA (IBS-D: 8.92 [2.33, 23.93] nmol/g, HC: 17.21 [8.76, 33.48] nmol/g; P = 0.025) were significantly decreased in IBS-D patients compared to HCs. Defecation frequency was positively associated with CA ( r = 0.294, P = 0.030) and CDCA ( r = 0.290, P = 0.032) and negatively associated with DCA ( r = −0.332, P = 0.013) and LCA ( r = −0.326, P = 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 ( r = −0.459, P = 0.028) in IBS-D patients. Furthermore, the relative abundance of the family Ruminococcaceae was significantly decreas...

Aberrant Gut-To-Brain Signaling in Irritable Bowel Syndrome - The Role of Bile Acids

“…In a number of clinical studies, bile acid dyshomeostasis has been detected in individuals with IBS (summarized in Table 1 ). It has consistently been reported that individuals with diarrhea-predominant IBS have elevated concentrations of fecal primary bile acids ( 57 – 60 , 62 , 63 ). Changes in bile acid profiles were also linked with IBS-D symptoms, such as the defecation frequency ( 57 , 58 , 61 , 62 ) and abdominal pain ( 60 , 62 , 63 ).…”

“…It has consistently been reported that individuals with diarrheapredominant IBS have elevated concentrations of fecal primary bile acids (57-60, 62, 63). Changes in bile acid profiles were also linked with IBS-D symptoms, such as the defecation frequency (57,58,61,62) and abdominal pain (60,62,63). The link with IBS-C is not as strong, although fecal LCA was decreased in this subset of individuals (58).…”

Review article: current and future treatment approaches for pain in IBS

“…29 Altered bile acid metabolism in the gut lumen observed in IBS-D patients was associated with both visceral hypersensitivity and microbiotic changes as another potential therapeutic target. 30 Increased intestinal membrane permeability was associated with hypersensitivity to somatic and visceral stimuli in a subset of patients with IBS-D 31 and barrier dysfunction is associated with abdominal pain in many IBS-D studies. 32 Gut sensory neural ion channels and ion channel receptors from human mucosal biopsies in IBS, their cross-talk as a whole cellular system, and between adjacent cells, likely contribute to visceral hypersensitivity.…”

Gut Microbiota-Derived Metabolites in Irritable Bowel Syndrome

“…C4 (7- α -hydroxy-4-cholesten-3-one) is positively associated with FGF19 and total BAs in IBS-D individuals, which indicates that the loss of BAs in feces leads to an increase in BA production. Moreover, patients with IBS-D have a higher proportion of Escherichia coli and decreased Clostridium leptum and Bifidobacterium ( Table 1 ) ( Duboc et al., 2012 ; Dior et al., 2016 ; Wei et al., 2020 ). However, a recent study showed that 24.5% IBS-D patients presented with a higher level of total BAs and Clostridia bacteria ( Zhao et al., 2020 ).…”