Recent studies have revealed bidirectional communication between the gut and muscles, in which irisin and muscle-derived brain-derived neurotrophic factor (BDNF) may mediate the positive effects of PA on certain aspects of AD pathophysiology through interactions with the gut microbiome ecosystem, neuroplasticity, anti-inflammatory signaling pathways, and neurogenesis (Cutuli et al., 2023; Sanchez-Martinez et al., 2024). The gene discussed is FNDC5; the disease is Alzheimer disease.