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Updated: Jun 19, 2026
Murine Model of Wound Healing
Published on: May 28, 2013
Androgen deprivation promotes diabetic wound healing in mice through modulation of wound microbiome and immune
Ziyang Sun1, Rizhong Huang2,3, Jingyi Chen1
1Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Clinical College, Nanjing University of Chinese Medicine, Nanjing, China.
Introduction:
Delayed wound healing is a major complication of diabetes, often associated with chronic inflammation and microbial dysbiosis. Although androgens are known to impair wound repair, their role in diabetic wound healing, particularly in regulating the local wound microbiome and associated immune response, remains poorly understood. In this study, we investigated whether androgen deprivation via surgical castration could enhance diabetic wound healing by modulating local microbial communities and inflammation.
Methods:
A full-thickness wound model was established in db/db mice. Surgical castration was used to achieve androgen deprivation. Wound closure and histology were assessed longitudinally. Blood glucose and body weight were monitored. The local immune microenvironment was profiled, focusing on pro-inflammatory factors and macrophage polarization. 16S rRNA sequencing characterized α-diversity and community composition over time. Functional prediction analyses inferred microbial metabolic potential, and machine-learning models evaluated taxa associated with healing dynamics.
Results:
Androgen deprivation significantly accelerated wound closure and improved histological outcomes without altering blood glucose or body weight. The wound microenvironment showed reduced pro-inflammatory factors and enhanced M2 macrophage polarization. 16S rRNA sequencing revealed increased microbial α-diversity and durable shifts in community composition, most prominently during early healing. Escherichia-Shigella, Rhodococcus, and Ochrobactrum were enriched, while Staphylococcus abundance decreased. Functional prediction indicated elevated microbial metabolic activity after castration. Machine-learning analysis identified Escherichia-Shigella as a key genus associated with accelerated healing.
Discussion:
Low androgen levels were associated with improved diabetic wound repair, potentially by attenuating local inflammation and fostering a more diverse, metabolically active microbiota. These data support a mechanistic link among androgens, wound inflammation, and the microbiome, and suggest host-directed therapeutic strategies for chronic diabetic wounds.
Insights
Androgen deprivation significantly improved diabetic wound healing by reducing inflammation and altering the gut microbiome. This suggests a new therapeutic approach for chronic diabetic wounds by targeting androgen levels.
Area of Science:
- Endocrinology
- Microbiology
- Immunology
Background:
- Delayed wound healing is a significant complication in diabetes, linked to chronic inflammation and microbial imbalances.
- Androgens are known to impede wound repair, but their specific role in diabetic wound healing, including microbiome and immune regulation, is unclear.
Purpose of the Study:
- To investigate if androgen deprivation through surgical castration enhances diabetic wound healing.
- To determine if castration modulates the local wound microbiome and inflammatory responses in diabetic mice.
Main Methods:
- A full-thickness wound model was created in diabetic (db/db) mice, with surgical castration used for androgen deprivation.
- Wound healing, histology, blood glucose, body weight, immune microenvironment (cytokines, macrophage polarization), and microbial composition (16S rRNA sequencing) were assessed.
- Machine-learning models identified microbial taxa associated with healing dynamics.
Main Results:
- Androgen deprivation accelerated wound closure and improved histology without affecting metabolic parameters.
- Castration reduced pro-inflammatory factors, promoted M2 macrophage polarization, and increased microbial diversity in wounds.
- Key bacterial genera like *Escherichia-Shigella* were enriched, correlating with accelerated healing, while *Staphylococcus* decreased.
Conclusions:
- Lower androgen levels are associated with enhanced diabetic wound repair, likely via reduced inflammation and a more diverse, active microbiome.
- These findings establish a mechanistic link between androgens, inflammation, and the microbiome in diabetic wound healing.
- Host-directed therapies targeting androgens may offer new strategies for managing chronic diabetic wounds.
