Fractyl’s pioneering Metabolic Balance Model identifies new model of intestine’s role in metabolism

Fractyl Health has announced the publication of an innovative new model of metabolism, the Metabolic Balance Model. The study synthesises multiple streams of existing evidence from molecular biology through clinical observations to build a new paradigm for understanding the role of the small intestine in metabolic disease. The company believes the Metabolic Balance Model is one of the most comprehensive frameworks in this field, and this latest publication represents a paradigm shift in our understanding of metabolism and the gut’s role in obesity and metabolic disease. The article, ‘A Gut-Centric Model of Metabolic Homeostasis’, is published in the October issue of the Journal of Diabetes Science and Technology.

“Within the past three months, we have seen several publications from leading scientists that are filling in important understanding of the pathology in the lining of the gut caused by high fat and sugar diets, leading to metabolic diseases. We’re pleased to have partnered with some of the leading experts in type 2 diabetes research to produce this new paradigm for understanding the causal mechanism relating these gut changes to metabolic disease, based on pioneering research by Fractyl Health and others,” said Dr Harith Rajagopalan, co-founder and CEO of Fractyl Health and the paper’s lead author. “Taking a fresh look at how we might correct the imbalance in the gut is necessary if we want to make a real difference in the lives of patients.”


The Metabolic Balance Model identifies the proximal small intestine as an important target and highlights the key role it plays in nutrient sensing and signalling, and the critical importance of the relationship between the proximal and distal small intestine in establishing the balance required to remain metabolically healthy. Diets that are high in easily digested fats and sugars have been hypothesised to cause an overgrowth of the lining of the proximal small intestine, which may lead to an imbalance in nutrient sensing and signalling between the proximal and distal small intestine. It is this imbalance, which came to the attention of Fractyl Health’s founders, that then led to the company’s pursuit of therapeutic approaches that can potentially correct the hormonal signals from the intestine and stem the tide of metabolic diseases in society.


“I have spent my career trying to better understand the underlying mechanisms of metabolic diseases in the body. Insights over the past 10 years have allowed us to reframe our understanding and elevate the role of the gut as a critical regulator of metabolism,” said Dr Alan Cherrington, professor of medicine, the Jacquelyn A Turner and Dr Dorothy J Turner chair in diabetes research, Vanderbilt University School of Medicine, and one of the paper’s authors. “What is exciting to me is that we now have a model for understanding the role of the gut that allows us to imagine how to potentially reverse metabolic disease by targeting this critical organ.”