Ultra-Processed Foods, Gut Microbiome, and Chronic Disease Risk: Chemical Analysis of Controlled Diets and Implications for Glucose Homeostasis in Mid-Life Adults

Abstract

Aging is associated with increased risk of type 2 diabetes (T2D), with prediabetes present in 45- 50% of mid-life adults. Ultra-processed food (UPF) are associated with T2D, cardiovascular disease, and other disease states. UPF's may adversely affect the gut microbiome, leading to chronic inflammation which can impair insulin signaling, however, randomized controlled trials are lacking in this research area. Controlled diets emphasizing either UPF (81% total energy) or non-UPF (0% total energy) were developed and chemically analyzed to ensure accurate matching across macronutrients, and various micronutrients. We also explored differences in other nutrients, not accounted for in our matching protocol. To test for causal relationships between UPF intake and T2D risk mediated by changes in the gut microbiome, a pilot trial (n=15) was conducted. After a 2-week standardized lead-in diet (59% UPF), adults aged 40-65 years were randomly assigned the high- or non-UPF diet for 6 weeks. Measurements of glucose tolerance, insulin sensitivity, 24- hr and postprandial glycemic control, glycemic variability, and fecal short chain fatty acids were made before and following the 6-week intervention period. Our results indicated a trend toward impaired glycemic variability (mean amplitude of glycemic excursions [MAGE]) (high-UPF: 37.6±10.1mg/dL to 40.2±7.3mg/dL; non-UPF:44.5±11.0 mg/dL to 39.3±9.5mg/dL, p=0.055) and glucose tolerance (glucose area under the curve [AUC] during OGTT) (high-UPF: 13431±3914mg·min/dL to 13656±4005mg·min/dL; non-UPF: 15349±4068mg·min/dL to 14221±3722mg·min/dL, p=0.054) following the high-UPF diet. Larger-scale trials are needed to confirm these findings.