Research Article: Sex-dependent modulation of acute respiratory distress syndrome by Bacteroides acidifaciens : gut microbiome impact on lung inflammation
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 ?? 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.
Introduction:
Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by severe lung inflammation, increased alveolar permeability, and impaired gas exchange ( 1 , 2 ). It is commonly triggered by infections, trauma, or sepsis and carries a high risk of morbidity and mortality ( 3 ). The COVID-19 pandemic has underscored the devastating impact of ARDS, as severe cases of SARS-CoV-2 infection frequently progress to ARDS, significantly contributing to hospitalizations and fatalities ( 4 ). Studies…
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