Aiding Patients of Irritable Bowel Syndrome with a Novel Gut Microbiota-mediated Mechanism

Project Overview

Irritable bowel syndrome (IBS), which is characterised by irregular defecation and abdominal pain, is one of the most prevalent functional gastrointestinal disorders worldwide. However, the incomplete pathogenic understanding of the disorder largely limits the development of effective and precise medication for IBS. A team of IBS researchers led by Professor Bian Zhaoxiang, Tsang Shiu Tim Endowed Chair of Chinese Medicine Clinical Studies and Director of the Clinical Division of the School of Chinese Medicine and the Hong Kong Chinese Medicine Clinical Study Centre, have discovered the mechanism by which altered gut microbiota can induce excessive bile acid (BA) synthesis and excretion in diarrhoea-predominant IBS (IBS-D). Their research findings were recently published in the internationally renowned academic journal The Journal of Clinical Investigation (https://jci.org/articles/view/130976).

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An excess of faecal BAs is thought to be one of the peripheral mechanisms for IBS-D, but the factors causing excessive BA excretion remain insufficiently studied. The team focused its investigation on the population of IBS-D patients with bile acid diarrhoea and identified a specific association between Clostridia bacteria enrichment and the levels of faecal BAs and serum BA synthetic and feedback markers. Through a series of basic experiments, they found that Clostridia-produced secondary BAs can suppress intestinal BA feedback regulation by targeting farnesoid X receptor signalling. As a result, this study enables a more precise pathogenic understanding of the disorder and the symptom management of IBS-D. Besides, the research strategy of integrating the profiling of gut microbiota with metabolic features will enable a deeper understanding of all microbiota-associated conditions, and not just IBS, by looking at the physiological, pathophysiological and therapeutic aspects. More importantly, given the importance of gut microbiota in the metabolism and pharmacology of herbal medicine, this study will also provide the basis for the development of Chinese medicines for IBS and other gut microbiota-related disorders.

The project is a collaboration with Professor Lyu Aiping, Dean of Chinese Medicine and the Dr. Kennedy Y.H. Wong Endowed Chair of Chinese Medicine, and Professor Jia Wei, Chair Professor in Chinese Medicine and Systems Biology and the Cheung On Tak Endowed Professor in Chinese Medicine, as well as Professor Cai Zongwei, the Kwok Yat Wai Endowed Chair of Environmental and Biological Analysis from the Department of Chemistry. A bioinformatics team led by Dr Fang Xiaodong, from the Second Affiliated Hospital of the Guangzhou University of Chinese Medicine, and Professor Hani El-Nezami, from the School of Biological Sciences at The University of Hong Kong, have also lent their support to this project.