Date of Award
Fall 2025
Document Type
Open Access Dissertation
Department
Biomedical Science
First Advisor
Kiesha Wilson
Second Advisor
Brandon Busbee
Abstract
Acute respiratory distress syndrome (ARDS) and colitis are severe inflammatory disorders marked by barrier dysfunction, dysregulated immunity, and limited therapeutic options. Increasing evidence implicates the gut microbiome in modulating these conditions through the gut–lung and gut–immune axes, yet the role of individual taxa and the modifying influence of biological sex remain incompletely defined. This dissertation investigates Bacteroides acidifaciens (BA), a commensal bacterium with potent immunomodulatory properties, as a context-dependent driver of inflammation in both intestinal and pulmonary settings.
Using dextran sulfate sodium (DSS)–induced colitis and Staphylococcal enterotoxin B (SEB)–induced ARDS models in male and female C3H/HeJ mice, we show that BA exerts strikingly divergent, sex-dependent effects. In colitis, BA exacerbates disease in females—inducing greater weight loss, colon shortening, and mucosal injury—yet confers partial protection in males by mitigating tissue damage and preserving body weight. In ARDS, BA colonization similarly worsens outcomes in females, aggravating lung pathology, neutrophil influx, cytokine storm, and intestinal barrier breakdown, whereas in males it attenuates disease by enhancing barrier integrity, dampening proinflammatory cytokines, and promoting IL-22–mediated repair pathways.
Mechanistic analyses identified immunoglobulin A (IgA) activation and estrogen signaling as key contributors to female-biased susceptibility, supported by the finding that estrogen suppression with letrozole mitigated BA-driven ARDS exacerbation. Multi-omics integration revealed sex-specific shifts in microbial composition, metabolite signaling, and host transcriptional pathways that align with these divergent outcomes.
Collectively, this work establishes BA as a powerful, context-dependent modulator of mucosal immunity whose effects are dictated by host sex, hormonal milieu, and tissue environment. By uncovering mechanistic links between estrogen, IgA, microbial metabolism, and barrier function, this dissertation advances understanding of how commensal microbes can act as either protectors or pathobionts. These findings underscore the necessity of incorporating sex as a biological variable in microbiome research and point toward precision medicine strategies that consider hormone–microbe–immune interactions in designing microbiota-targeted therapies for inflammatory diseases.
Rights
©2025, Shanieka Caroline Staley
Recommended Citation
Staley, S. C.(2025). Sex-Dependent Modulation of Dss-Induced Colitis and Seb-Induced ARDS by Bacteroides Acidifaciens. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/8687