Abstract
Background: Bile acid diarrhoea (BAD) is common, often unrecognised, or thought to be irritable bowel syndrome with diarrhoea (IBS-D). It results from increased loss of bile acids (BAs) into the colon but mechanisms are unclear. The gut microbiota plays key roles in the metabolism of primary BAs to form secondary BAs, which have differing impacts on intestinal metabolism and homeostasis. The aim of this study was to profile the gut microbiome in BAD and to investigate the differences in bacterial metabolic products and specific bile acids. Methods: Patients with BAD diagnosed by SeHCAT testing, were compared with other IBS-D patients, and healthy controls. Faecal 16S ribosomal RNA gene analysis was undertaken. Faecal short chain fatty acid (SCFA) and urinary fermentation metabolite profiles (volatile organic compounds; VOCs) were measured. BAs were quantified in serum and faeces. Findings: Faecal bacterial diversity was significantly reduced in patients with BAD, but several taxa were enriched compared to IBS-D. SCFA amounts differed in BAD, controls and IBS-D, with significantly more propionate in BAD. Separation of VOC profiles was evident between all groups with the greatest discrimination between IBS-D and controls. Unconjugated and primary BA in serum and faeces were significantly higher in BAD. The proportion of faecal primary BA was inversely related to SeHCAT values. Interpretation: BAD results in dysbiosis, with differences in metabolites including VOC, SCFA and higher concentrations of primary BAs when compared to IBS-D. These findings provide new mechanistic insights into the pathophysiology of BAD. Funding Statement: Funding was from UHCW Trust’s charity as well as the Midlands Gastroenterology Society and Bardhan Research and Education Trust (BRET). Declaration of Interests: JW has been a consultant for, and reports institutional grant funding from GE Healthcare, and Prometheus diagnostics. RA has delivered educational talks for GE Healthcare. No disclosures are made by all authors Ethics Approval Statement: Scientific and ethical approval was acquired from the local Research and Development Office as well as Warwickshire Ethical committee ref: 09/H1211/38. Written informed consent was obtained from all participants in the study.
Highlights
Bile acid diarrhoea (BAD) is a common disorder resulting from increased loss of bile acids (BAs), overlapping irritable bowel syndrome with diarrhoea (IBS-D)
Taxa identified from these operational taxonomic units (OTUs) showed, at the phylum level, that Firmicutes were most abundant in IBSD, but in BAD they were more reduced compared to the reduction of Bacteroidetes (Fig. 1B)
Most families, including Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae were lower in abundance in BAD, but there were increases in Prevotellaceae and Verrcomicrobiaceae (Fig. 1C) Differences in the abundances of many OTUs were found, but the statistical significances of these were not robust when p values were adjusted for multiple comparisons
Summary
Bile acid diarrhoea (BAD) is a common disorder resulting from increased loss of bile acids (BAs), overlapping irritable bowel syndrome with diarrhoea (IBS-D). BAD produces dysbiosis, with metabolite differences, including VOC, SCFA and primary BAs when compared to IBS-D. These findings provide new mechanistic insights into the pathophysiology of BAD. Bile acid diarrhoea (BAD) is a commonly missed cause of chronic diarrhoea and has been demonstrated in excess of a quarter of patients who were previously diagnosed with IBS-D1,2. Unabsorbed primary BAs can undergo biotransformation by the microbiota in the colon, to form the secondary BAs, deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA). These are partially absorbed passively in the colon, or excreted in the faeces[5]. Increased faecal primary BAs have been demonstrated in IBS-D and have been suggested as a diagnostic biomarker for BAD10–13
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