The Gendered Microbiome: A Women’s History Focus

Almost 30 years ago the NIH Revitalization Act of 1993 mandated the inclusion of women and people of color in clinical research, promoting more diverse and relevant health data.

The inclusion of women in microbiome studies has expanded understanding of host-microbe interactions, contributing to novel therapeutic strategies and precision medicine approaches.

Recent studies on women’s gut health reveal how hormonal differences shape microbiota composition, emphasizing the need for more tailored research.

The composition of the adult gut microbiota is influenced by various factors, including diet, genetics, hormones, environmental conditions, drugs, lifestyle and even stress. Gender-based differences in gut microbiota also exist, influenced by factors like hormonal levels, immune responses, ethnicity, body mass index (BMI) and age. Additionally, microbes of the same species can produce different metabolites based on the host's gender and sex hormones, leading to distinct effects (Marano et al., 2023). As the gut microbiota develops throughout life, it interacts with the immune and nervous systems, resulting in different microbial communities and immune pathways in adult men and women.

Recent studies show mixed results on sex differences in gut microbiota. Generally, females tend to have higher α-diversity—referring to the richness and evenness of microbial species that reflect the overall complexity of the gut microbiome. However, differences in specific microbial taxa remain inconsistent. In Western studies, females tend to have higher levels of Bifidobacterium, a favorable bacteria which has been linked to improvements in digestion, metabolic health and which may have a protective effect against conditions like inflammatory bowel diseases (IBD). Higher abundance of Bifidobacterium in females, as seen in some studies, may reflect its role in supporting gut health, particularly in relation to other microbial species. Males, on the other hand, often have more Gemmiger formicilis or Prevotella, which play a role in nutrient processing, and whose concentrations may be diet related. Notably, sex differences were more evident in individuals with enteric infections, with females having higher Bacteroides, which aid in inflammation regulation, and males having more Escherichia, which are involved in pathogen defense (Kim et al., 2020).

Emerging research is enhancing our understanding of women’s gut health by revealing the impact of reproductive hormones, particularly estrogen, on the gut microbiome. Estrogen, produced by various tissues, can be metabolized by gut microbes which affects the host. In post-menopausal women and men, estrogen levels are linked to microbiota diversity and specific microbial taxa. Non-ovarian estrogens are influenced by the microbiome and enzymes like β-glucuronidase, which affect estrogen metabolism.

Estrogen and testosterone also influence immune cell function, leading to pro-inflammatory cytokine production and altered gut permeability, which can promote inflammation. This research emphasizes how hormonal changes throughout a woman’s life can significantly affect gut health and immune responses (Yoon, 2021).

Increased focus on women's microbiome research has driven breakthroughs in maternal health, pregnancy outcomes and disease prevention (Pereira et al., 2022). Studies have linked microbiome composition to conditions like preterm birth, gestational anemia and thyroid disorders, shaping new diagnostic and therapeutic strategies (Kumar et al., 2021; Wu et al., 2021). The inclusion of women in microbiome studies has expanded understanding of host-microbe interactions, contributing to novel therapeutic strategies and precision medicine approaches (Zakaria et al., 2022). As research continues to evolve, these insights underscore the importance of sex-specific microbiome studies in shaping the future of biomedical science (Balch, 2024). These advancements reflect a growing recognition of the microbiome’s role in shaping women's health across history and into the future.