Evolutionary History With Chronic Malnutrition Enhances Pathogen Susceptibility at Older Ages

Juvenile malnutrition is a global public health concern that negatively impacts the development and maturation of the immune system, leading to increased susceptibility to infectious diseases. Such adverse effects on immunity might increase with ageing, worsening disease conditions later in life. Furthermore, malnutrition may persist across generations, imposing strong natural selection to survive the nutrient shortage. However, it is unclear how the evolutionary history of ancestral generations with chronic malnutrition could influence pathogen resistance and infection susceptibility, as well as their age-specific changes in extant generations. To address this, we used <i>Drosophila melanogaster</i> populations adapted to chronic juvenile malnutrition and exposed them to a bacterial pathogen, <i>Providencia rettgeri</i>, during their early and late adulthood. Surprisingly, we observed that in populations adapted to chronic malnutrition, young flies survived infection better by tolerating the infection, while control flies displayed higher infection susceptibility despite carrying a similar pathogen load. However, this pattern in post-infection survival is reversed with ageing. There was no change in pathogen resistance, but evolved flies succumbed more to infection than control flies regardless of the input infection doses. Our study thus revealed new evolutionary insights into the development of contrasting early-late-life immune strategies and age-specific vulnerabilities to infection as a function of early-life malnutrition.