Unraveling the intersection between nutrition and lung viral infection

Respiratory infections including influenza virus and SARS-CoV-2 are a leading cause of global mortality and morbidity. Individuals exhibit a large variety in infection outcomes that is likely linked to differences in genetics and environmental factors such as nutrition. Nutrition has a major impact on human health, yet how past consumption of specific diets affects disease outcomes remains largely unknown. A person's diet shapes their microbiota, however, if and how different diets leave persistent changes in an individual's microbial composition and host metabolism remains uncharacterized. In this study we aim to assess the relevance of diet history for outcomes of lung viral infection. We will firstly evaluate whether diets of different nutrient composition including those with high calorie and high fibre contents affect the severity of lung infection. In parallel we will profile the changes induced in the composition of gut microbes and their metabolic capacity, including systemic molecules that could directly regulate lung infection. We will then assess whether the role of diet history in infection is dependent on these changes in the microbiota. Finally, we will delve into the molecular mechanisms of how diet-induced persistent changes in systemic molecules modulate antiviral immunity, including mediating epigenetic and functional changes in key antiviral immune cells. This will establish nutrition history as a new critical factor in explaining an individual's likelihood of developing severe disease after lung viral infection, potentially paving the way for novel metabolite-based precision medicines.