Iron Homeostasis and Reproduction: Unveiling the Microbiome–Gut–Brain Axis Connection in the Mosquito Anopheles culicifacies

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.