The connection between the gut microbiome, the estrobolome, hormonal signaling, and inflammatory skin disease is increasingly framed within the broader concept of the gut- skin axis, a bidirectional network linking microbial metabolism, immune function, and endocrine pathways.

Gut microbiome and the gut- skin axis

The gut microbiome plays a central role in regulating systemic inflammation, immune tolerance, and metabolic signaling. Disruptions (dysbiosis) can promote inflammatory skin conditions such as acne, rosacea, and atopic dermatitis (eczema). Mechanistically, gut microbes produce metabolites (e.g., short-chain fatty acids) that influence:

• intestinal barrier integrity
• systemic cytokine levels
• skin immune responses

These hormonal shifts are particularly relevant in:

• acne (androgen-driven sebum and keratinocyte proliferation)
• rosacea and eczema, where estrogen signaling influences vascular and immune responses

Estrobolome and hormonal modulation

A key subset of the gut microbiome is the estrobolome that consists of bacteria capable of metabolizing estrogens via enzymes such as β- glucuronidase. This regulates the balance between active and inactive estrogen in circulation.

Dysbiosis can therefore alter:

• Estrogen levels (via impaired deconjugation/recycling)
• Androgen & estrogen balance
• Downstream sebum production and inflammation

mTOR pathway as a central integrator

The mTOR (mechanistic target of rapamycin) pathway acts as a nutrient- and hormone-sensitive signaling hub
linking microbiome activity to skin physiology.

• Gut microbial metabolites can regulate mTOR signaling, affecting lipid synthesis, cell growth, and inflammation.
• Overactivation of mTORC1 is strongly implicated in acne pathogenesis.
• Dysbiosis may amplify mTOR signaling through metabolic and inflammatory feedback loops.

Thus, the microbiome- mTOR axis provides a mechanistic bridge between diet, hormones, and skin disease

Evidence from randomized controlled trials (RCTs)

Although much of the field remains mechanistic and observational, several RCTs support a causal role of the gut microbiome in skin disease:

• A randomized controlled trial in rosacea (2024) showed that probiotic supplementation following antibiotics significantly improved clinical outcomes and modulated gut–skin microbial interactions.
• Earlier RCTs in acne and atopic dermatitis have demonstrated that oral probiotics
  can:
  • reduce inflammatory lesion counts
  • improve skin barrier function
  • decrease systemic inflammatory markers

These trials collectively support the idea that modifying the gut microbiome can influence dermatologic disease severity.

Integration: a unified model

The current evidence supports a multi-layered model:
1.Gut dysbiosis leads to altered microbial metabolites and increased gut permeability
2.Estrobolome disruption impairs estrogen metabolism resulting in hormonal imbalance
3.Hormonal + metabolic signaling leads to activation of pathways like mTOR
4.Immune dysregulation causes systemic and cutaneous inflammation
5. Clinical expression is seen as acne, rosacea, eczema

These trials collectively support the idea that modifying the gut microbiome can influence dermatologic disease severity.

Bibliography
1. Yu, J., et al. (2024). Effects of probiotic supplementation on gut–skin axis in rosacea: A randomized controlled trial. mSystems.
2.Jung, G. W., et al. (2013). Prospective, randomized, open-label trial comparing the efficacy of probiotics in the treatment of acne vulgaris. Journal of Cutaneous Medicine and
Surgery, 17(2), 114–122.
3. Kim, J., Ko, Y., Park, Y. K., Kim, N. I., & Ha, W. K. (2010). Dietary effect of lactoferrin-enriched fermented milk on skin surface lipid and clinical improvement of acne
vulgaris: A randomized, double-blind, placebo-controlled trial. Nutrition, 26(9), 902–909.
4. Navarro-López, V., et al. (2018). Efficacy and safety of oral administration of a mixture of probiotic strains in patients with atopic dermatitis: A randomized controlled trial.
Journal of Dermatological Science, 90(3), 281–288.
5.Bowe, W. P., & Logan, A. C. (2011). Acne vulgaris, probiotics and the gut–brain–skin axis: From anecdote to translational medicine. Beneficial Microbes, 2(3), 185–199.
6. Plottel, C. S., & Blaser, M. J. (2011). Microbiome and malignancy: The estrobolome and estrogen metabolism. Journal of Clinical Oncology, 29(27), 3727–3733.
7. Melnik, B. C. (2018). Acne vulgaris: The metabolic syndrome of the pilosebaceous follicle. Clinical, Cosmetic and Investigational Dermatology, 11, 291–304.
8. Salem, I., Ramser, A., Isham, N., & Ghannoum, M. A. (2018). The gut microbiome as a major regulator of the gut–skin axis. Frontiers in Microbiology, 9, 1459.
9. O’Neill, A. M., & Gallo, R. L. (2018). Host–microbiome interactions and recent progress into understanding the biology of acne vulgaris. Microbiome, 6(1), 177.
10. De Pessemier, B., et al. (2021). Gut–skin axis: Current knowledge of the interrelationship between microbial dysbiosis and skin conditions. Microorganisms, 9(2), 353.

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* This post was originally printed in the Village Medicine Seattle’s Wellness Quarterly Magazine, 2Q26 Edition. Read and download the full publication

About The Author

Dr. Tiffany Jaramillo is a Naturopathic Physician and practitioner at Village Medicine Seattle. Tiffany loves empowering, educating, and reconnecting patients to their inner wisdom. Learn more about Dr. Jaramillo