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Monitoring Gut Microbiome, Vitamin D, and Hormonal Axis: Not Just a Seasonal Strategy for Immune Resilience
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By Jeannie Gorman, MS, CCN | October 28, 2025
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As fall and winter approach, clinicians face an annual convergence of seasonal stressors that challenge immune homeostasis: reduced ultraviolet B (UVB) sunlight exposure, dietary shifts away from fresh, microbiota supportive foods, and heightened viral circulation. Without proactive intervention, these factors can destabilize a pivotal set of interdependent elements in immune regulation to include: gut microbiota composition, short chain fatty acid (SCFA) production, Vitamin D₃ (VD₃) metabolism, hormonal influences and conditions involving compromised skin barrier integrity. Together, these elements constitute a unified framework for mucosal immunity across multiple organ systems.
Since 2020, COVID 19 protocols have accelerated research into the synergistic relationship between VD₃ and gut microbial composition in modulating immune resilience, particularly in older adults, post infectious recovery, and chronic inflammatory states. A 2025 systematic review in Nutrition Reviews analyzed 14 randomized controlled trials finding that VD₃ supplementation consistently improved gut microbial diversity and shifted composition toward beneficial phyla (Firmicutes, Actinobacteria, and Bacteroidetes). These changes were associated with enhanced immune regulation and reduced inflammation. The findings reinforce the role of VD₃ in shaping the gut microbiome and suggest that targeted supplementation may help mitigate immunosenescence, the gradual decline in immune function with age, via gut microbial balance and mucosal immunity. Even with adequate serum 25(OH)D (inactive precursor form), a dysbiotic microbiome or diminished SCFA output may impair conversion to 1,25(OH)₂D (active hormone-like form) that binds to the vitamin D receptor (VDR) and drives immune regulation. This disruption can blunt anti-inflammatory signaling and reduce VDR expression, limiting VD₃’s immunological benefits.
Respiratory infections such as SARS-CoV-2, influenza, and pneumonia, along with reactivating viruses like shingles (herpes zoster), disrupt microbiome diversity, impair SCFA-producing bacteria, and increase proinflammatory species. These disruptions weaken mucosal immunity and delay recovery, particularly in older and immunocompromised populations. Compounding this, sex hormones also influence microbial diversity and VD₃ metabolism. Estrogen upregulates 1 alpha hydroxylase, the enzyme converting 25(OH)D to its active form, 1,25(OH)₂D, and enhances VDR expression, amplifying immunomodulatory effects, especially in postmenopausal women. Testosterone may prolong VD₃ activity by downregulating 24 hydroxylase, the enzyme that degrades 1,25(OH)₂D, and may contribute to higher baseline 25(OH)D levels in men due to its effect on lean body mass as a VD₃ reservoir.
These internal disruptions are further compounded by external factors such as skin barrier dysfunction, which plays a central role in common conditions like atopic dermatitis, psoriasis, and acne vulgaris. In these disorders, impaired epidermal integrity allows for increased microbial penetration, local inflammation, and systemic immune activation. Although most research has examined gut-derived effects on skin health, microbial imbalance at one mucosal site may disrupt barrier integrity and trigger inflammation at another, exemplifying the gut–skin axis (GSA). Emerging evidence shows that UVB exposure to the skin can beneficially influence gut microbiota and intestinal function, underscoring the interconnected nature of immune regulation across epithelial surfaces.
An ongoing personalized approach to immune support, integrating gut microbiome status, vitamin D levels, hormonal context, and patient specific risk factors is warranted. Because of its long half-life, measurement of total 25-Hydroxyvitamin D (D2 plus D3) provides the best assessment of vitamin D status and includes vitamin D derived from diet, supplements and exposure to UVB light. Strategies combining targeted therapeutics with testing gut microbiome, salivary or urinary hormones, and serum or bloodspot 25-Hydroxyvitamin D offer a promising path to delaying immune aging, reducing chronic inflammation, and improving resilience to respiratory infections across clinical settings.
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- Falak Zeb, Tareq Osaili, Mona Hashim, Nadia Alkalbani, Dimitrios Papandreou, Leila Cheikh Ismail, Farah Naja, Hadia Radwan, Hayder Hasan, Reyad Shakir Obaid, Ioannis Savvaidis, Sharifa AlBlooshi, Iftikhar Alam. Effect of Vitamin D Supplementation on Human Gut Microbiota: A Systematic Review of Randomized Controlled Trials. Nutrition Reviews. 2025; nuaf120. https://doi.org/10.1093/nutrit/nuaf120
- Waterhouse M, Hope B, Krause L, et al. Vitamin D and the gut microbiome: a systematic review of in vivo studies. Eur J Nutr. 2019;58:2895–2910. https://doi.org/10.1007/s00394-018-1842-7
- Bellerba F, Muzio V, Gnagnarella P, Facciotti F, Chiocca S, Bossi P, Cortinovis D, Chiaradonna F, Serrano D, Raimondi S, Zerbato B, Palorini R, Canova S, Gaeta A, Gandini S. The Association between Vitamin D and Gut Microbiota: A Systematic Review of Human Studies. Nutrients. 2021;13(10):3378. https://doi.org/10.3390/nu13103378
- Bishop EL, Ismailova A, Dimeloe S, Hewison M, White JH. Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti-Inflammatory. JBMR Plus. 2021;5(1):e10405. https://doi.org/10.1002/jbm4.10405
- Doudou Guo, Xin Ning, Tao Bai, Lingfang Tan, Yanfen Zhou, Zhichen Guo, Xin Li. Interaction between Vitamin D homeostasis, gut microbiota, and central precocious puberty. Front Endocrinol. 2024;15. https://doi.org/10.3389/fendo.2024.1449033
- Santos-Marcos JA, Mora-Ortiz M, Tena-Sempere M, et al. Interaction between gut microbiota and sex hormones and their relation to sexual dimorphism in metabolic diseases. Biol Sex Differ. 2023;14:4. https://doi.org/10.1186/s13293-023-00490-2
- van Schoor NM, Lips P. Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab. 2011;25(4):671–680. https://doi.org/10.1016/j.beem.2011.06.007
- Jimenez-Sanchez M, Celiberto LS, Yang H, Sham HP, Vallance BA. The gut-skin axis: a bi-directional, microbiota-driven relationship with therapeutic potential. Gut Microbes. 2025;17(1). https://doi.org/10.1080/19490976.2025.2473524
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A New Perspective on the Impact
of Menopausal Hormone Therapy
Presented by Heather Hydzik, ND | November 5, 2025 at 12 PM Pacific
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Since the 2002-2004 WHI trials linked hormone therapy to breast cancer, heart disease, and stroke, many women avoided treatment for menopausal symptoms. Later reanalysis (2008-2019) showed that early postmenopausal therapy lowered coronary disease and mortality, and estrogen alone reduced breast cancer risk-though this perspective never reached mainstream media. A 2024 study of 10 million women has further redefined hormone safety beyond age 65, highlighting risks and benefits by formulation and delivery. Urinary hormone testing can also reveal metabolism patterns tied to cancer risk. Together, these insights help clinicians individualize therapy to improve quality of life and longevity.
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Learning Objectives:
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Update your knowledge on evolving perspectives of hormone therapy and breast risk
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Review WHI reanalysis showing different risks/benefits of estrogen than first reported
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Explore findings from a 2024 large-scale study of women >65 on cancer, CVD, dementia, and mortality
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Learn the safest hormone delivery methods and formulations
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Interpret urine hormone testing for breast health and risk reduction
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Review case examples with BHRT and a new non-hormonal option
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Hormones in Aging: Perimenopause, Menopause and Andropause
Presented by Lylen Ferris, ND | November 12, 2025 at 11 AM Pacific
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Menopause is a well-defined stage marked by the end of menstruation, while andropause reflects a more gradual change in testosterone in men. These natural life transitions may influence overall well-being and are part of the normal aging process. Developing a deeper understanding of these changes can help clinicians recognize patterns and provide informed, supportive care to patients.
In this session, Dr. Lylen Ferris, ND, Director of Clinical Education at Doctor's Data, will share perspectives on evaluating hormone balance with advanced laboratory assessments. The discussion will introduce two testing options from Doctor's Data - the Comprehensive Plus Salivary Hormone Profile and the Hormone & Urinary Metabolites Assessment Profile (HuMap™). Dr. Ferris will also review considerations for incorporating the cortisol awakening response (CAR) into salivary cortisol testing, along with lifestyle and nutrition factors that clinicians may wish to explore when supporting patients.
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Learning Objectives:
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How natural hormonal transitions associated with aging may influence overall health in both men and women
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The role of saliva and urine testing in providing insights about hormone balance
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General lifestyle and nutrition considerations relevant to hormonal transitions
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Disclaimer: All information given about health conditions, treatment, products, and dosages are for educational purposes only and do not constitute medical advice.
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800.323.2784 (US and Canada)
+1.630.377.8139 (Global)
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