Investigating alveolar stem cell loss and impaired lung repair in response to highly-processed diet

• Applicant: Timothy McCulloch, Ph.D.
• Subject Area: Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 556527736

Modern lifestyles often involve diets rich in highly processed foods. Emerging evidence indicates these diets harm health, leading to chronic diseases, inflammation, and immune dysfunction. Understanding how these dietary changes cause harm is crucial. In this study, we will model this in mice by comparing those fed a normal chow diet with those on a purified, processed diet. The normal chow diet is grain-based, representing a natural diet, while the purified diet, although calorically equal, consists of processed ingredients mimicking many contemporary human diets. Preliminary data suggest that mice on a processed diet are more susceptible to influenza infection than those on normal chow. These mice also show significantly reduced alveolar type II (AT2) cells, essential for lung repair and regeneration after injury, such as influenza infection. We hypothesize that a highly processed diet disrupts lung homeostasis, increasing infection susceptibility. This project aims to explore these phenotypes further to understand the mechanisms behind AT2 cell impairment and lung repair. We will use various methods to characterize lung architecture in response to a highly processed diet, including flow cytometry, histology, imaging techniques, and transcriptome analysis. Additionally, we will examine the metabolism of the whole organism and individual lung cell populations to observe how a processed diet causes these impairments. Our objectives are: a) To define the impact of a highly processed diet on lung structure and cellular composition; b) To investigate the metabolic changes induced by a processed diet at systemic and cellular levels; c) To determine the relationship between diet-induced metabolic alterations and lung repair mechanisms. We expect these data to provide a comprehensive understanding of how a highly processed diet affects lung health. Future work could reveal dietary, behavioral, or therapeutic interventions to promote lung health and infection resistance. This project is especially relevant given the rising consumption of processed foods and the ongoing threat of respiratory infections like influenza and SARS-CoV-2. By clarifying the links between diet, stem cell function, and lung repair, we aim to inform public health strategies and clinical practices to mitigate the negative effects of highly processed diets on respiratory health.

• DFG Programme: WBP Position