Redefining the biogeography and function of food proteins in human health and disease - food is central to human health

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Boston Children's Hospital $831,433 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), supporting research to redefine the biogeography and function of food proteins in human health and disease.

The project establishes first principles of the food-host interactome by developing systematic approaches to map the transit, transformation, and tissue distribution of thousands of food-derived compounds in the body using stable isotope-labeled plants. The research redefines the role of dietary proteins in human health and disease, moving beyond conventional understanding of protein function limited to nutrition and proximal gut absorption. Work includes developing technically innovative and unbiased approaches to capture the location, digestion, and biological interface of structurally and functionally diverse food proteins, with particular relevance to chronic diseases including inflammatory bowel disease, celiac disease, malnutrition, kidney disease, metabolic disorders, and obesity.

Performance period runs from September 1, 2026, through June 30, 2031, at Boston Children's Hospital in Boston, Massachusetts. The award is classified as a Project Grant, the standard assistance type for NIH extramural biomedical research supporting investigator-initiated studies of scientific merit competing for available funds through peer review.

What we eat is increasingly linked to chronic diseases such as IBD, celiac disease, malnutrition, kidney disease, metabolic disorders and obesity, areas critical to the niddk mission. Understanding which and how the components of food impact heath and disease is imperative toward leveraging our diet for disease prevention and management. Yet when we begin to ask what food is composed of, we are immediately overwhelmed by the vast complexity of food composed of the thousands of natural and artificial components of food, both known and unknown. The broad and diverse range of food molecules challenges US to understand which components of food impact human health and how these molecules interface with molecular, cellular, tissue, and organ systems. In this proposal for a niddk catalyst award, we aim to revolutionize our understanding of the food-host relationship by developing systematic, cutting-edge, and unbiased approaches towards establishing a new and rigorous science of food biology and redefining our concepts of food protein in human health and disease. In aim 1 we seek to establish the first principles of the food-host interactome, establish a biogeographic atlas of whole food molecules using stable isotope-labeled plants, defining the transit, transformation, and tissue distribution of thousands of food-derived compounds in the body. We will then turn to redefine the role of dietary proteins in human health and disease, liberating the field from the conceptual limitations of the 'central dogma of food protein' in which food protein is monolithic in function (NUTRITIONAL) and location (absorbed in the proximal GUT). In aim 2, we will develop and apply technically innovative and unbiased approaches to capture the location, digestion, and critically, biological interface of the structural and functional diverse food proteins of our diet. In aim 3, we will reveal the GUT microbiome as the second digestive organ for food protein, defining the landscape of food protein digestion by the GUT microbiome, discover microbiome-derived food protein digestive enzymes, and in proof-of-concept in vivo studies in nutrition and celiac disease lay the foundation for harnessing food protein digestion by the GUT microbiome for the management of diseases central to mission of the niddk. If successful, this niddk catalyst funded work will create a chemical atlas of food throughout the body, informing new links between the components of food and human health and establish new paradigms of both the function of food protein and food protein-microbiome interactions. Our work will lay the foundation to leverage the previously unexplored and newly revealed functional diversity of food proteins and the microbiome for translational application in human health and disease.