A New Paradigm in the Relationship between Melatonin and Breast Cancer: Gut Microbiota Identified as a Potential Regulatory Agent
Open accessAbstract
In this review we summarize a possible connection between gut microbiota, melatonin production, and breast cancer. An imbalance in gut bacterial population composition (dysbiosis), or changes in the production of melatonin (circadian disruption) alters estrogen levels. On the one hand, this may be due to the bacterial composition of estrobolome, since bacteria with β-glucuronidase activity favour estrogens in a deconjugated state, which may ultimately lead to pathologies, including breast cancer. On the other hand, it has been shown that these changes in intestinal microbiota stimulate the kynurenine pathway, moving tryptophan away from the melatonergic pathway, thereby reducing circulating melatonin levels. Due to the fact that melatonin has antiestrogenic properties, it affects active and inactive estrogen levels. These changes increase the risk of developing breast cancer. Additionally, melatonin stimulates the differentiation of preadipocytes into adipocytes, which have low estrogen levels due to the fact that adipocytes do not express aromatase. Consequently, melatonin also reduces the risk of breast cancer. However, more studies are needed to determine the relationship between microbiota, melatonin, and breast cancer, in addition to clinical trials to confirm the sensitizing effects of melatonin to chemotherapy and radiotherapy, and its ability to ameliorate or prevent the side effects of these therapies.
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Levels of gut melatonin can be anywhere from 10 to 100 times greater than melatonin in blood serum levels.
“Levels of gut melatonin can be anywhere from 10 to 100 times greater than melatonin in blood serum levels [37,38].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [38]
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References 108 · Cited by 28
Research works printed but not linked: 1
- [46]Cos S. González A. Alvarez Garcia V. Alonso-Gonzalez C. Martinez-Campa C. Melatonin and Breast Cancer: Selective Estrogen Enzyme Modulator Adv. Cancer Drug Targets 2012 1 207 237 19075592
- Authors
- Laborda-Illanes, A., Sánchez-Alcoholado, L., Boutriq, S., Plaza-Andrades, I., Peralta-Linero, J., Alba, E., González-González, A., & Queipo-Ortuño, M. I.
- Affiliations
- Instituto de Investigación Biomédica de Málaga (ES)
- Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, Spain
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Corresponding author
- Alba, Emilio
- González-González, Alicia
- ORCID
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2021-06-23
- Volume
- 13
- Issue
- 13
- Pages
- 3141
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC8269379
- OpenAlex
- W3175171549
- Cited by
- 28
- References
- 108
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 3 · 2022: 8 · 2021: 1
- FWCI
- 0.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Consejería de Salud de la Junta de Andalucía (PE-0106-2019)
- Fundación Unicaja (C19047-2018)
- UMA-FEDER (UMA18-FEDERJA-042)
- Consejería de Salud (C-0030-2018), Junta de Andalucía (Regional “Nicolas Monardes” research program)
- ALIANZA MIXTA EN RED ANDALUCÍA-ROCHE EN ONCOLOGÍA MÉDICA DE PRECISIÓN (INVESTIGACIÓN BÁSICA/TRASLACIONAL) (-)
- Consejería de Salud y Familia (co-funded by the Fondo Europeo de Desarrollo Regional-FEDER) (Predoctoral grant (PE-0106-2019))
- ISCIII and co-funded by the Fondo Europeo de Desarrollo Regional-FEDER (Predoctoral grant PFIS-ISCIII (FI19-00112))
- ISCIII, co-funded by the Fondo Europeo de Desarrollo Regional-FEDER (“Miguel Servet Type II” program (CPI13/00003))
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- melatonin, breast cancer, gut microbiota, dysbiosis, estrobolome, beta-glucuronidase, estrogen metabolism, circadian rhythm disruption, kynurenine pathway, tryptophan metabolism, adipogenesis, aromatase, antiestrogenic effects
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