A probiotic that degrades imidazole propionate, a proinflammatory histidine metabolite common to numerous chronic diseases

Moonshot Award

Product or Company Development

Abstract

Imidazole propionate (ImP), a gut microbiota-derived metabolite of histidine, has emerged as a key player in multiple chronic diseases including type 2 diabetes (T2D) obesity and hypertension, atherosclerosis, coronary artery disease, chronic kidney disease and neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Mechanistically, ImP disrupts insulin signaling, promotes endothelial dysfunction, and exacerbates inflammatory pathways. 

Our goal is to engineer a probiotic bacterium able to degrade ImP. We have cloned the gene hutI from Stenotrophomonas maltophila which endcodes and enzyme for degradation of ImP and expressed it in E. coli. We are currently evaluating the ability of HutI to degrade ImP.