# Genetic and dietary determinants of gut microbiome-bile acid interactions in the BXD genetic reference population

## TL;DR

This study explores how genetics and diet influence gut microbiome and bile acid interactions in mice, offering insights into microbiome-host communication.

## Contribution

The study identifies diet-dependent genetic loci and potential candidate genes modulating gut microbiome-bile acid interactions.

## Key findings

- Genetic and dietary factors alter microbiome composition and gut microbiome-bile acid crosstalk in BXD mice.
- Four diet-dependent co-mapping genetic loci, including Turicibacter sanguinis - plasma cholic acid interaction, are identified.
- Candidate genes PTGR1 and PTPRD are prioritized for their potential role in regulating gut microbiome-bile acid interactions.

## Abstract

The gut microbiome is crucial in regulating overall physiology and communicates with the host through various microbial-derived metabolites, including secondary bile acids (BAs). However, mechanisms underlying the gut microbiome-BA crosstalk (gMxB) are still poorly understood. Here, we assess the postprandial cecal microbiome, BA levels, and colon transcriptome of male BXD mice fed with a chow or high-fat diet, and find that genetic and dietary factors shift microbiome composition and affect gMxB. Four diet-dependent co-mapping genetic loci associated with gMxB, including the interaction between Turicibacter sanguinis - plasma cholic acid, are identified using systems genetics approaches. By integrating human MiBioGen database, we prioritize PTGR1 and PTPRD as candidate genes potentially regulating identified gMxB. The human relevance of these candidates on metabolic health is investigated using data from the UK biobank, FinnGen, and million veteran program databases. Overall, this study illustrates potential modulators regulating gMxB and provides insights into gut microbiome-host communication.

The authors show that genetic and dietary factors reshape the microbiome and influence gut microbiome–bile acid crosstalk. They also identify potential modulators and offer insights into microbiome–host communication.