ACE Inhibitors on the Microbiome and Host Energy Balance

John W. Walsh, University of Iowa


Lisinopril and captopril are ACE Inhibitors class drugs used for lowering blood pressure and are widely prescribed for efficacy in treating high blood pressure and for its manageable side effects. However, captopril, not lisinopril, has been shown to cause weight loss in murine models. The endocrine system that modulates blood pressure, the Renin-Angiotensin System (RAS) has been shown to regulate energy balance. The microbiome is the vast ecosystem of microbes that live in the large intestine and help modulate various aspects of host physiology including metabolism, and has been shown to be susceptible to alterations by xenobiotics. Our lab has previously show that xenobiotic intervention with risperidone can shift the microbiome, which suppresses host anaerobic resting metabolism. This study has shown that captopril, not lisinopril, causes a significant loss in weight in mice after one week of treatment compared to lisinopril and control treatment. This weight loss is contributed to an increase in energy output, which may implicate shifts in the gut microbiome as a cause of the weight differential. We believe that this weight loss is caused by an increased non-aerobic metabolic rate due to a shifted microbiome. If further testing confirms this, research in this field could lead to treatment options for obesity and its related diseases that target the gut microbiome for those unable to lose weight on conventional diets and current weight loss medication.