Study Reveals INSL5 Hormone's Role in Chronic Diarrhea Linked to Bile Acid Malabsorption

A recent study conducted by researchers at the University of Cambridge has unveiled a significant link between high levels of the gut hormone Insulin-Like Peptide 5 (INSL5) and chronic diarrhea, particularly in patients suffering from bile acid malabsorption. Published in the prestigious journal *Gut*, the research offers profound insights into the underlying mechanisms of this condition, which reportedly affects around 1% of the population, and has implications for the diagnosis and treatment of irritable bowel syndrome (IBS) with diarrhea as a predominant symptom.

Chronic diarrhea, defined by the frequent passage of loose or watery stools, can be debilitating and is often misdiagnosed. As noted by Dr. Chris Bannon, the lead author of the study and a clinical fellow at the Institute of Metabolic Science at the University of Cambridge, many patients are incorrectly diagnosed with IBS when they actually experience bile acid diarrhea. This condition occurs when bile acids are not adequately reabsorbed in the intestines, leading to their presence in the colon, which in turn causes irritation and diarrhea.

The research utilized a novel antibody test developed in collaboration with pharmaceutical company Eli Lilly, allowing scientists to quantify INSL5 levels in patients. The findings demonstrated that individuals with bile acid diarrhea exhibited significantly elevated INSL5 levels compared to healthy volunteers. Dr. Bannon remarked, "The higher the INSL5 levels, the more severe the diarrhea symptoms, suggesting that this hormone plays a critical role in the condition."

The study analyzed data from several sources, including a previous investigation carried out at the University of Adelaide, which had examined the effects of bile acid enemas on healthy subjects. The results indicated that such treatments not only triggered the release of another gut hormone, GLP-1, but also resulted in increased INSL5 levels, further supporting the hypothesis that INSL5 is a key player in bile acid-induced diarrhea.

Dr. Julian Walters from Imperial College London provided additional patient samples for the study, revealing that approximately 40% of IBS patients with previously ruled-out bile acid malabsorption had raised INSL5 levels. This finding underscores the complexity and often overlapping nature of gastrointestinal conditions, highlighting the need for more precise diagnostic tools.

The implications of this research are manifold. Currently, treatment options for bile acid diarrhea primarily involve bile acid sequestrants, which are effective in only two-thirds of patients. The exploration of INSL5 as a potential biomarker could pave the way for the development of more targeted therapies. Dr. Bannon emphasized the importance of understanding gut hormones, stating, "Gut hormones have been neglected in research, yet they play crucial roles in digestive health and response to toxins."

The study received funding from the Medical Research Council and Wellcome Trust, as well as support from the National Institute for Health and Care Research's Cambridge Biomedical Research Centre. As the research progresses, the team aims to further investigate the mechanisms of INSL5 and its potential as a therapeutic target. This study not only sheds light on the biological processes underlying chronic diarrhea but also raises awareness of the challenges faced by patients navigating the complexities of gastrointestinal disorders.

As the scientific community continues to explore the intricate relationships between gut hormones and gastrointestinal health, this groundbreaking research stands to inform both clinical practice and future investigations, potentially leading to improved diagnostic methods and treatment options for those suffering from chronic diarrhea related to bile acid malabsorption.