Jacob Hiatt, 2026 MGM Distinguished Fellows Travel Award Recipient

Jacob Hiatt
David Lab
Digestive Disease Week (DDW) 2026 in Chicago, Illinois
May 2-5, 2026

Abstract:
DNA is a ubiquitous yet understudied dietary macromolecule that enters the gastrointestinal (GI) tract with every meal, with average daily intake ranging from 1-20g per day depending on dietary composition. Ultraprocessed foods, which are being increasingly consumed worldwide, are depleted of DNA. This shift in nutritional composition has unknown physiologic consequence. Dietary DNA may provide nucleotides for cellular function and metabolism, including epithelial renewal, immune activation, microbial metabolism, and essential cofactor synthesis. Yet, the digestive mechanisms generating these substrates, and the consequences of insufficient dietary DNA intake, remain poorly understood. We hypothesize that the majority of ingested dietary DNA is degraded through the GI tract to provide nucleotides for host and microbial use. To assess the persistence of DNA throughout the GI tract, we designed a quantitative PCR assay targeting a conserved plant chloroplast gene (trnL). In both mice and pigs---two species differing in gastrointestinal architecture---more than 99% of ingested DNA was degraded to fragments <100 bp by the stomach and proximal small bowel. Our results suggest a conserved digestive mechanism for reducing dietary DNA to simpler metabolic substrates. Sequencing of trnL amplicons revealed different proportions of plant dietary DNA along the GI tract, suggesting different degradation rates between dietary sources. To determine how dietary composition influences DNA degradation across the GI tract, we compared four nutritionally distinct diets that varied in dietary DNA quantities. Despite substantial differences in processing level and macronutrient content, all diets showed >90% degradation of dietary DNA in the stomach and small bowel, reinforcing the robustness of digestive mechanisms responsible for nucleotide liberation. Last, we examined DNA persistence in an antibiotic-induced depletion of the microbiome to assess microbial contributions to digestion. We found no difference in dietary DNA content along the GI tract when compared to an intact microbiome model, in contrast to the well-documented variability in digestion of other macromolecules. Together, these findings establish dietary DNA digestion as a conserved and efficient process across mammalian species, diets, and GI environments—distinct from the variable digestion of proteins, fats, and carbohydrates.