Gender differences in bacterial infection susceptibility stem from a complex interplay between sex hormones and gut microbiome composition. Estrogens enhance immune defenses while promoting beneficial bacteria like Bifidobacterium that produce protective short-chain fatty acids. Conversely, androgens and progesterone suppress immunity and reduce colonization resistance against pathogens. Males face greater severity with H. pylori gastritis and cholera, while females encounter heightened risks during reproductive phases for Listeria and Salmonella infections.
This hormonal-microbial axis represents a paradigm shift in understanding infectious disease patterns. The gut microbiome actively modulates hormone levels through enzyme activity, creating feedback loops that influence pathogen virulence and host susceptibility. For C. difficile recurrence and E. coli infections, these mechanisms prove particularly consequential. The research opens pathways for precision medicine approaches, including sex-stratified diagnostic protocols using microbiome sequencing and targeted probiotic interventions. Rather than treating infections as gender-neutral conditions, clinicians may soon personalize antimicrobial strategies based on hormonal status and microbiome profiles, potentially improving outcomes for both prevention and treatment of bacterial infections across diverse patient populations.