Intrahepatic cholestasis of pregnancy (ICP) is characterised by increased maternal serum total bile acids (TBA) and symptoms, including pruritus, in women without known active liver disease. In severe ICP with TBA ≥100 mmol/L, risks of stillbirth are increased. The gut microbiome is an important regulator of BA metabolism through the conversion of primary BA into secondary BA, which can signal through the TGR5 receptor. Standard treatment for ICP is ursodeoxycholic acid (UCDA) but this is not always effective. The TURRIFIC trial is an RCT comparing the effects of UCDA with rifampicin (RIF), an antibiotic with capacity to reduce TBA outside of pregnancy. In TURRIFIC, stool samples are collected throughout pregnancy for analysis of the gut microbiome.
We compared the effect of treatment with UCDA against RIF on the composition of the gut microbiome in 13 women with ICP, 5 of whom were treated with UCDA and 8 with RIF. We conducted metagenomic sequencing at 3 GB depth. Sequencing data was analysed with the MetaPhlAn pipeline for taxonomy and HuMaN3 for function. Differential abundance was determined using MaAsLin2 and adjusted for multiple testing.
Interindividual variability was extensive. Treatment with RIF significantly reduced alpha diversity in both taxonomic and functional analyses, whereas beta diversity was altered only at the taxonomic level. RIF treatment decreased the abundance of Ruminococcus bromii, Romboutsia and Candidatus_Cibionibacter compared with that of UCDA-treated or untreated ICP. There were, however, no significant changes to the functional pathways or to antibiotic-resistance gene abundance in the microbiomes between the groups.
The results of this study show that, in this small cohort, there was no major effect on the composition of the gut microbiome or on antibiotic-resistance gene carriage in response to treatment of women with ICP with RIF rather than UCDA. Larger studies may be required to detect any significant differences.