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Males frequently exhibit heightened severity in conditions like\n                    <jats:italic toggle=\"yes\">Helicobacter pylori<\/jats:italic>\n                    -associated gastritis and\n                    <jats:italic toggle=\"yes\">Vibrio cholerae<\/jats:italic>\n                    outbreaks, whereas females face amplified risks during reproductive phases for pathogens, such as\n                    <jats:italic toggle=\"yes\">Listeria monocytogenes<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                    spp. Beyond genetic and behavioral factors, the bidirectional sex hormone\u2013gut microbiome axis emerges as a key mechanistic driver: estrogens bolster innate immunity and microbial diversity (e.g., enriching short-chain fatty acid-producing taxa like\n                    <jats:italic toggle=\"yes\">Bifidobacterium<\/jats:italic>\n                    ), while androgens and progesterone impose immunosuppressive effects, altering colonization resistance and virulence modulation. Microbial contributions\u2014via \u03b2-glucuronidase-mediated hormone deconjugation, bile acid biotransformations, and metabolite signaling\u2014further calibrate host responses, as evidenced in\n                    <jats:italic toggle=\"yes\">Clostridioides difficile<\/jats:italic>\n                    recurrence and enterohemorrhagic\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    virulence upregulation. This review synthesizes epidemiological, preclinical, and emerging clinical data, highlighting the axis\u2019s role in pathogen-specific immune evasion and dysbiosis-driven exacerbations. Clinically, these insights advocate for sex-stratified microbiome diagnostics (e.g., 16S rRNA sequencing for risk profiling) and targeted therapies, including hormone-modulated probiotics to restore barrier function, fecal microbiota transplantation to curb antibiotic-associated vulnerabilities, and selective estrogen receptor modulators to enhance clearance in high-risk cohorts. Despite advances, gaps in human longitudinal studies and pathogen-strain interactions limit translation. Future research integrating multi-omics with clinical trials could refine precision interventions, optimizing infection management in diverse populations and aligning with evolving demands for personalized microbiology.\n                  <\/jats:p>","DOI":"10.1128\/cmr.00236-25","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T14:00:19Z","timestamp":1763647219000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["The sex hormone-gut microbiome axis: mechanistic drivers of sex-disparate bacterial infection outcomes and precision clinical interventions"],"prefix":"10.1128","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7157-9012","authenticated-orcid":false,"given":"Li","family":"Tang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00f809463","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Systems Health 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