Manipulating the microbiome : an alternative treatment for bile acid diarrhoea

Bile acid diarrhoea (BAD) is a widespread gastrointestinal disease that is often misdiagnosed as irritable bowel syndrome and is estimated to affect 1% of the United Kingdom (UK) population alone. BAD is associated with excessive bile acid synthesis secondary to a gastrointestinal or idiopathic disorder (also known as primary BAD). Current licensed treatment in the UK has undesirable effects and has been the same since BAD was first discovered in the 1960s. Bacteria are essential in transforming primary bile acids into secondary bile acids. The profile of an individual’s bile acid pool is central in bile acid homeostasis as bile acids regulate their own synthesis. Therefore, microbiome dysbiosis incurred through changes in diet, stress levels and the introduction of antibiotics may contribute to or be the cause of primary BAD. This literature review focuses on primary BAD, providing an overview of bile acid metabolism, the role of the human gut microbiome in BAD and the potential options for therapeutic intervention in primary BAD through manipulation of the microbiome

Can manipulating the microbiome be used to treat bile acid diarrhoea?

Primary bile acid diarrhoea (BAD) is a prevalent gastrointestinal disease that affects approximately 1% of the UK population. It is characterised by chronic watery diarrhoea, bloating, pain and bowel incontinence. The current licensed treatment in the UK has unwanted side effects and has remained unchanged since BAD was first discovered in the 1960s. Excessive bile acid synthesis is associated with BAD, and the profile of an individual’s bile acid pool is central in bile acid homeostasis as bile acids regulate their own synthesis. Bacteria are essential in transforming primary bile acids into secondary bile acids and microbiome dysbiosis caused by changes in diet, stress levels, and antibiotics may contribute to the development of the disease. The findings presented in this thesis demonstrate a strong association between disease severity and reduced microbial diversity in patients with BAD. Our analysis highlights significant differences in the microbial composition of BAD patients' stool compared to healthy individuals. Furthermore, functional gene analysis reveals that BAD patients exhibit a higher relative abundance of bile acid transforming genes than healthy controls. Our study also uncovers a higher presence of biofilm-related genes and species in the stool of patients with BAD. Our findings suggest that changes in whole gut transit time have a significant impact on the composition and function of the gut microbiota, as well as on bile acid metabolism. These results shed light on the critical role of bile acids in their own regulation and provide insights into the uncontrolled synthesis of bile acids observed in patients with BAD. In conclusion, the results presented in this thesis, along with recent research, provide compelling evidence supporting the therapeutic potential of the human gut microbiome in the treatment of BAD