The pathophysiology of bile acid diarrhoea: differences in the colonic microbiome, metabolome and bile acids

Nidhi M Sagar,Christopher Quince,James A Covington,Alfian N Wicaksono,Henri Duboc,Julian R F Walters,Konstantinos Gerasimidis,Vaios Svolos,Ramesh P Arasaradnam,Gemma L Kay,Lola J Palmieri,Margarita Kokkorou,Mohammad T Alam

doi:10.1038/s41598-020-77374-7

Abstract

Bile acid diarrhoea (BAD) is a common disorder resulting from increased loss of bile acids (BAs), overlapping irritable bowel syndrome with diarrhoea (IBS-D). The gut microbiota metabolises primary BAs to secondary BAs, with differing impacts on metabolism and homeostasis. The aim of this study was to profile the microbiome, metabolic products and bile acids in BAD. 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 volatile organic compounds (VOCs) were measured. BAs were quantified in serum and faeces. Faecal bacterial diversity was significantly reduced in patients with BAD. 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, but the greatest discrimination was between IBS-D and controls. Unconjugated and primary BA in serum and faeces were significantly higher in BAD. The faecal percentage primary BA was inversely related to SeHCAT. 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.

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

Introduction

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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