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Updated: Jun 3, 2025
An Intestinal Gut Organ Culture System for Analyzing Host-Microbiota Interactions
Published on: June 30, 2021
Sex-dependent gastrointestinal colonization resistance to MRSA is microbiota and Th17 dependent
Abstract:
Gastrointestinal (GI) colonization by methicillin-resistant Staphylococcus aureus (MRSA) is associated with a high risk of transmission and invasive disease in vulnerable populations. The immune and microbial factors that permit GI colonization remain unknown. Male sex is correlated with enhanced Staphylococcus aureus nasal carriage, skin and soft tissue infections, and bacterial sepsis. Here, we established a mouse model of sexual dimorphism during GI colonization by MRSA. Our results show that in contrast to male mice that were susceptible to persistent colonization, female mice rapidly cleared MRSA from the GI tract following oral inoculation in a manner dependent on the gut microbiota. This colonization resistance displayed by female mice was mediated by an increase in IL-17A+ CD4+ T cells (Th17) and dependent on neutrophils. Ovariectomy of female mice increased MRSA burden, but gonadal female mice that have the Y chromosome retained enhanced Th17 responses and colonization resistance. Our study reveals a novel intersection between sex and gut microbiota underlying colonization resistance against a major widespread pathogen.
Insights
Female mice rapidly clear gut methicillin-resistant Staphylococcus aureus (MRSA) via microbiota-dependent mechanisms involving Th17 cells and neutrophils. This sex-based difference highlights a novel interaction between host immunity, gut microbes, and pathogen colonization.
Area of Science:
- Microbiology
- Immunology
- Sex Differences in Disease
Background:
- Gastrointestinal colonization by methicillin-resistant Staphylococcus aureus (MRSA) poses significant transmission and invasive disease risks.
- Factors governing MRSA gastrointestinal colonization, particularly sex-based immune responses, are poorly understood.
- Male sex is linked to increased Staphylococcus aureus infections and sepsis.
Purpose of the Study:
- To investigate sexual dimorphism in a mouse model of gastrointestinal MRSA colonization.
- To elucidate the immune and microbial mechanisms underlying colonization resistance in female mice.
Main Methods:
- Oral inoculation of mice with MRSA to establish a gastrointestinal colonization model.
- Comparative analysis of MRSA burden in male and female mice.
- Assessment of immune cell populations (Th17, neutrophils) and microbiota composition.
- Evaluation of the impact of ovariectomy on colonization resistance.
Main Results:
- Female mice rapidly cleared MRSA from the GI tract, while male mice exhibited persistent colonization.
- Colonization resistance in females was dependent on the gut microbiota.
- Enhanced Th17 cell responses and neutrophil activity mediated resistance in females.
- Ovariectomy diminished colonization resistance in females, but gonadal status and Y chromosome presence did not abrogate resistance.
Conclusions:
- Host sex significantly influences gut colonization resistance against MRSA.
- A complex interplay between gut microbiota, Th17 immunity, neutrophils, and sex hormones dictates MRSA colonization.
- This study uncovers a novel mechanism of colonization resistance at the intersection of sex and the gut microbiome.
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