Feeding the invaders: how metabolic imbalance shapes infection and biofilm development

Infectious and metabolic disorders have risen sharply and pose a significant threat to human populations worldwide. Despite being deemed unrelated, mounting evidence indicates that metabolic disorders markedly heightened both the likelihood and severity of infectious disease. The mechanism underlying this association is only beginning to be appreciated and involves a complex interaction between altered metabolic state, pathogen virulence mechanisms, and immune effector pathways. Here, we highlight that a dysregulated metabolic environment disrupts homeostasis, creating a nutrient-rich, immunocompromised milieu that promotes bacterial survival and replication in the host. Metabolic dysfunction is also discussed as a factor that promotes bacterial persistence by altering reactive oxygen species production and inducing tissue hypoxia, conditions that favor biofilm growth. We also examine how bacteria directly exploit nutrient surplus in metabolic diseases to boost their virulence programs and biofilm formation. Moreover, given the ever-increasing problem of antibiotic resistance, we discuss how metabolic diseases contribute to this challenge. Collectively, uncovering how metabolic disorders increase chronic or recurrent infections can guide the development of effective treatment strategies.