AUTHOR=Staley Shanieka , Walkup Virginia , Oxendine Stacey , Mauya Zannatul , Williams Jordan , Busbee Philip Brandon , Wilson Kiesha 

TITLE=Sex-dependent modulation of acute respiratory distress syndrome by Bacteroides acidifaciens: gut microbiome impact on lung inflammation

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653309

DOI=10.3389/fimmu.2025.1653309

ISSN=1664-3224

ABSTRACT=Bacteroides acidifaciens (BA), a common gut commensal, is known to modulate immune responses, but its role in acute respiratory distress syndrome (ARDS) and potential sex-specific effects remain poorly understood. To investigate this, male and female mice were colonized with BA prior to induction of ARDS using dual doses of staphylococcal enterotoxin B (SEB), a potent superantigen that triggers cytokine storm–driven lung injury. Clinical parameters, histopathology, gene expression, ELISA, flow cytometry, and gut barrier assessments were used to evaluate outcomes. BA pre-treatment significantly improved lung function, and attenuated pulmonary inflammation in male mice, correlating with increased IL-22, expansion of γδ T cells, and upregulation of colonic tight junction proteins. In contrast, BA exacerbated ARDS symptoms in females, increasing Th17 responses, neutrophil infiltration, and IgA-associated immune activation while impairing gut barrier integrity. These findings reveal that BA exerts divergent, sex-dependent effects in ARDS, highlighting the critical need to consider sex as a biological variable in microbiome-based therapies targeting inflammatory lung disease.