Shaping Healthy Immune Early Life Dynamics: role of the virome in undernutrition

ongoing

Nearly half of all deaths in children under five are linked to undernutrition, which causes developmental issues and increased susceptibility to infections and intestinal inflammation that are not fully corrected by traditional nutrition strategies. Early exposure to commensal bacteria shapes immune trajectories, influencing susceptibility to infections and inflammatory diseases both early in life and in the long-term. Reseach from the host laboratory has demonstrated that commensal bacteria contribute to host development, particularly under conditions of undernutrition. Similarly, commensal viruses (aka the virome) can modulate immune responses. Infants, especially in regions with high rates of undernutrition, are highly exposed to these viruses. However, the virome’s impact on immune development and its contribution to the effects of undernutrition remains largely unexplored. Building on my experience working with a commensal murine enteric virus, I aim to investigate how early immune imprinting by the virome alters host-development trajectories —including growth, metabolism, and sexual maturation—and affects long-term susceptibility to infections and inflammatory diseases in male and female mice. Using a combined approached of hypothesis-driven research (focusing on the homeostatic role of type I interferons) and a RNA sequencing-based discovery, this study will uncover unknown physiological functions of immune cells that are critical in challenging environments like undernutrition. The findings from this study will provide new insights into how understudied factors—such as the virome, sex, and undernutrition—affect immune function, including host-defenses and physiological functions. This knowledge could lead to innovative preventive and therapeutic strategies for undernourished children, such as microbiota-targeted food and immune-based interventions, tailored specifically for boys and girls.