Key exposome and gender-related risk factors in ADs.
| Category | Specific factor | Mechanism/effect | Gender differences | References |
|---|---|---|---|---|
| Environmental | Industrialised lifestyle (urbanisation, pollution) | Alters immune responses; increases risk of ADs | Affects both sexes; potentially greater impact on women | [76, 82, 83] |
| Environmental | Pollutants, chemicals | Disrupt immune homeostasis | May affect hormonal metabolism differently | [76] |
| Nutrition | Western diet (refined carbs, fats, red meat) | Promotes systemic inflammation; alters microbiota | Greater effect in women with economic hardship | [91, 92] |
| Nutrition | Micronutrient deficiency | Impairs immune regulation; breaking of self-tolerance | More common in women, especially in low-income settings | [21, 91] |
| Nutrition | Anti-inflammatory foods (polyphenols, omega-3) | Improve immune tolerance by reducing AD risk | Intake varies by culture and gendered dietary patterns | [92, 98] |
| Microbiome | Dysbiosis (imbalance of gut flora) | Reduces tolerance to self-antigens; increases inflammatory responses | Sex-specific patterns are linked to hormones and life stages | [21, 96, 97] |
| Microbiome | Early-life microbial exposure | Shapes long-term immune responses | Influenced by birth method, breastfeeding, and hygiene habits | [99, 100] |
| Microbiome | Pregnancy-associated microbiome shifts | Alters the immune landscape; may trigger ADs | Unique to women | [96] |
| Infections | Reduced exposure to microbes (hygiene hypothesis) | Impaired immune training; increased risk of hypersensitivity and autoimmunity | More pronounced in high-income countries | [82, 92] |
| Infections | Molecular mimicry (e.g., EBV, Coxsackievirus) | Cross-reactivity between pathogen and self-antigens triggers ADs | Gender-biased susceptibility in some diseases | [96] |
| Infections | Protective infections (protozoa, fungi, commensals) | Induce regulatory pathways; suppress autoimmune responses | Under study, the gender effect is less defined | [82] |
| Socioeconomic | Food and water insecurity | Increases malnutrition, infection risk; impairs microbiome | Women and children are most affected | [21, 100] |
| Socioeconomic | Health care access and education | Affects exposure, treatment, nutrition, and microbial environment | Gender gap often presents in access and outcomes | [21, 41] |
ADs: autoimmune diseases; EBV: Epstein-Barr virus.
AC: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. GA: Writing—review & editing. AA: Writing—review & editing. RZ: Investigation, Writing—original draft, Writing—review & editing. GC: Conceptualization, Investigation, Writing—original draft, Writing—review & editing, Supervision. All authors read and approved the submitted version.
Giuseppina Candore, who is the Editorial Board Member of Exploration of Immunology, had no involvement in the decision-making or review process of this manuscript. The other authors declare that they have no conflicts of interest.
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