Iron Homeostasis and Reproduction: Unveiling the Microbiome-Gut-Brain Axis Connection in the Mosquito Anopheles...

Our study investigated how adult female Anopheles culicifacies mosquitoes regulate systemic iron homeostasis after blood feeding, a process essential for reproduction, and revealed striking parallels to iron deficiency disorders in mammals. This study identifies that coordinated transcriptional regulation of ferritin and transferrin plays a crucial role in follicle development and egg maturation. Silencing of both genes using ribonucleic acid interference led to severe reproductive impairment, including ovarian arrest in 50% of females, a 40% reduction in oocyte number, and a decrease in first instar larval size. These outcomes correlate with increased reactive oxygen species and altered serotonin receptor expression in the brain, possibly driven by alterations in microbial gut-brain axis communication due to disrupted iron metabolism. In summary, our research provides the first molecular proof and a new conceptual understanding of how iron metabolism disorders may affect microbiome-gut-brain-axis communication and, in turn, reproductive outcomes.