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Discovery of novel bile acid-modifying genes in the human gut microbiome
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Trillions of microorganisms reside in the human gut and play essential roles in human health. The collective genomes of all these microorganisms are known as the “gut microbiome”. A research group led by prof. Jingyuan Fu of the UMCG conducted research into new genes that give insight in the role of the microbiome in the development of diseases. The researchers discovered bile acid-modifying genes in the gut microbiome. The discovery of these genes will contribute to the development of microbiome-targeted approaches to regulate human bile acid metabolism.

The role of the microbiome in disease development 

In the past few years, we have learned a great deal about the role of the microbiome. A decreased diversity or imbalanced composition of the microbiome can lead to diseases such as obesity and its co-morbidities, for example. An approach to identify microbial genes that are relevant to human health and disease was lacking. This knowledge gap greatly limits our understanding of the role of the microbiome in the etiology of human diseases and hampers the development of microbiome-based therapeutic approaches. 
This study focused on natural occuring genetic variations in the bacterial genome aiming to find new genes. The researchers had a particul interest in structural variations, which refer to various segments of bacterial genomes that are either deleted or present in varyng copy numbers. By linking these to data from two Dutch cohorts, LifeLines-DEEP and 300-Obesity, the researchers discovered bile acid-modifying genes in the gut microbiome.

Important implications for human health 

These findings may have important implications for human health. Bile acids are produced in the liver and expelled in the intestine after a meal, where their structure can be modified by bacteria. Bile acids are known to promote formation of bile and to facilitate absorption of dietary fats and vitamins from the intestine. More recently, it was discovered that these molecules also have hormone-like functions and display specific roles in regulation of glucose and lipid metabolism and in control of immune functions. Importantly, the different bile acid species that are present in the human body have different properties in this respect. 

Treatment for liver and cardiometabolic diseases are emerging

Therapeutic approaches targeting bile acid metabolism for treatment of liver and cardiometabolic diseases are emerging. The findings of this study will contribute to the development of microbiome-targeted approaches to regulate human bile acid metabolism.

This study is published in Cell Host & Microbe, a leading journal in the microbiome research field, on the 29th of November, 2021. This study is supported by the Dutch Heart Foundation (DHF, IN-CONTROL II), ERC Consolidator, and NWO-VICI grants.