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Probiotics and Endometriosis

Did you know that almost 1 million Australian girls, women, and those assigned female at birth suffer from endometriosis at some point in their lives?1 Endometriosis is an oestrogen-dependent, chronic inflammatory condition that causes significant pelvic and abdominal pain.2 Common symptoms include pain during intercourse (dyspareunia), infertility,  painful periods (dysmenorrhea), and ongoing pelvic discomfort. Despite being widely studied, the exact cause of endometriosis remains unclear.3 Recent research, however, has discovered a compelling relationship between gut microbiome and the progression of endometriosis.4 Specifically, the interaction between gut bacteria, oestrogen metabolism, and inflammation may play a key role in this complex condition.

The Oestrogen-Gut microbiome axis 

Within the gut resides the estrobolome, which is a collection of microbial genes responsible for metabolising oestrogens. Certain gut bacteria, particularly Bifidobacterium and Lactobacillus species, produce enzymes such as β-glucuronidase and β-glucosidase, which deconjugate oestrogens and promote their reabsorption.5 This process promotes the reabsorption of free oestrogen, potentially increasing circulating oestrogen levels and contributing to hormonal balance in individuals with endometriosis. 

However, in cases of gut dysbiosis, this process may become disrupted, leading to excess oestrogen reabsorption.6 The result is a hyper-oestrogenic environment that may drive the abnormal growth of endometrial tissue and intensify pelvic pain associated with endometriosis.5,6

Gut microbiota, Inflammation and Immune Dysregulation

Beyond oestrogen metabolism, the gut microbiota also plays a key role in immune function and inflammation. In dysbiosis, the overgrowth of Gram-negative bacteria increases the production of lipopolysaccharide (LPS), a molecule known to compromise the gut barrier.7,8 When LPS enters the bloodstream, it activates immune responses through the TLR4/NF-κB signaling pathway, prompting the release of inflammatory cytokines like IL-6, TNF-α, and IL-8.7 

This inflammatory cascade contributes to pelvic pain, immune dysregulation, and the growth of ectopic endometrial tissue.7 Therefore, disturbances in gut microbiota may play a pivotal role in the onset and progression of endometriosis by modulating systemic inflammation and innate immunity.

Diet and Endometriosis Management

Effective endometriosis management requires a personalised, multidisciplinary approach, involving hormonal treatments, non-hormonal therapies, and lifestyle modifications.9 Among emerging non-drug options, dietary interventions have shown potential in alleviating endometriosis symptoms, particularly due to their impact on gut health, inflammation, and oestrogen regulation.10  

A systematic review has suggested that the Mediterranean diet, known for its high intake of omega-3 polyunsaturated fatty acids and antioxidant-rich foods, may help reduce endometriosis-associated pain.11 One of its core components, extra virgin olive oil, contains oleocanthal, a compound structurally similar to ibuprofen that inhibits cyclooxygenase (COX) enzyme production, thereby reducing inflammation and pain.11 

Additionally, the diet’s high fibre content supports digestive health and may promote hormonal balance by aiding oestrogen elimination through regular bowel movements, while magnesium-rich foods may contribute to uterine muscle relaxation by increasing intracellular calcium levels, potentially easing cramping and pelvic pain.12 Compared to more restrictive diets like low FODMAP or low-nickel protocols, the Mediterranean diet offers a more sustainable, long-term lifestyle change, offering not only symptom relief but also broad cardiometabolic and anti-inflammatory health benefits.11,

Probiotics and Their Therapeutic Potential

Recent studies suggest that probiotics, particularly certain strains of Lactobacillus, may offer adjunctive benefits in managing endometriosis through mechanisms such as immune modulation, enhancing gut barrier integrity, and reducing inflammation.13,14 For instance, Lactobacillus gasseri (OLL2809) has demonstrated immunoregulatory and anti-inflammatory effects in experimental models.14,15 Another randomised triple-blind, placebo-controlled pilot trial also found that oral Lactobacillus supplementation significantly reduced endometriosis-associated pain, reinforcing the potential role of probiotics as part of a broader management plan.16

While evidence is still emerging, current research highlights the potential of targeting the gut microbiome through diet and probiotic interventions as a complementary strategy in endometriosis management.7 Probiotics, particularly Lactobacillus strains, may help reduce inflammation and modulate oestrogen metabolism, offering symptom relief. Despite these findings, the field is still in its early stages. Most existing studies have small sample sizes or are preclinical. Larger-scale randomised controlled trials and mechanistic studies are needed to fully elucidate the role of specific probiotic strains, dosing regimens, and treatment durations in endometriosis. 

References:

  1. Endometriosis Australia. Insight into endometriosis.Date unknown. Accessed May 16 May, 2025. https://endometriosisaustralia.org/understanding-endometriosis/#:~:text=Insight%20into%20endometriosis,%2C%20joints%2C%20lungs%20and%20brain. 
  2. Giudice L.C. Clinical practice. Endometriosis. N Engl J Med. 2010;362:2389–2398. doi: 10.1056/NEJMcp1000274
  3. Burney R.O., Giudice L.C. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98:511–519. doi: 10.1016/j.fertnstert.2012.06.029.
  4. Jiang I., Yong P.J., Allaire C., Bedaiwy M.A. Intricate Connections between the Microbiota and Endometriosis. Int J Mol. Sci. 2021;22:5644. doi: 10.3390/ijms22115644.
  5. Possemiers S., Bolca S., Verstraete W., Heyerick A. The intestinal microbiome: a separate organ inside the body with the metabolic potential to influence the bioactivity of botanicals. Fitoterapia. 2011;82(1), 53–66. doi:  10.1016/j.fitote.2010.07.012
  6. Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas. 2017;103:45-53. doi: 10.1016/j.maturitas.2017.06.025.
  7. Guo C, Zhang CY. Role of the gut microbiota in the pathogenesis of endometriosis: a review. Front Microbiol. 2024;15.doi: https://doi.org/10.3389/fmicb.2024.1363455 
  8. Kaliannan, K., Wang, B., Li, XY. et al. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Sci Rep 5. 2015:11276. doi: https://doi.org/10.1038/srep11276 
  9. Qin R, Tian G, Liu J, Cao L. The gut microbiota and endometriosis: From pathogenesis to diagnosis and treatment. Front Cell Infect Microbiol. 2022;12:1069557. doi: 10.3389/fcimb.2022.1069557.
  10. Becker CM., Bokor A, Heikinheimo O, Horne A, Jansen ., Kiesel L, King K, Kvaskoff M, Nap A, Petersen K, et al. ESHRE guideline: Endometriosis. Hum Reprod Open. 2022;2022:hoac009. doi: 10.1093/hropen/hoac009
  11. Nirgianakis K, Egger K, Kalaitzopoulos DR, et al. Effectiveness of Dietary Interventions in the Treatment of Endometriosis: a Systematic Review. Reprod Sci. 2022; 29:26–42. doi: https://doi.org/10.1007/s43032-020-00418-w 
  12. Fomin VP, Gibbs SG, Vanam R, Morimiya A, Hurd WW. Effect of magnesium sulfate on contractile force and intracellular calcium concentration in pregnant human myometrium. Am J Obstet Gynecol. 2006;194(5):1384–90. Doi: https://doi.org/10.1016/j.ajog.2005.11.045.
  13. Xholli A, Cremonini F, Perugi I, Londero AP, Cagnacci A. Gut Microbiota and Endometriosis: Exploring the Relationship and Therapeutic Implications. Pharmaceuticals (Basel). 2023;16(12):1696. doi: 10.3390/ph16121696.
  14. Itoh, H., Sashihara, T., Hosono, A., Kaminogawa, S., and Uchida, M.Lactobacillus gasseri OLL2809 inhibits development of ectopic endometrial cell in peritoneal cavity via activation of NK cells in a murine endometriosis model. Cytotechnology. 2011;3:205–210. doi: 10.1007/s10616-011-9343-z
  15. Sashihara T, Sueki N, Furuichi K, Ikegami S. Effect of growth conditions of Lactobacillus gasseri OLL2809 on the immunostimulatory activity for production of interleukin-12 (p70) by murine splenocytes. Int J Food Microbiol. 2007;120(3):274-81. doi: 10.1016/j.ijfoodmicro.2007.09.003.
  16. Khodaverdi S, Mohammadbeigi R, Khaledi M, Mesdaghinia L, Sharifzadeh F, Nasiripour S, Gorginzadeh M. Beneficial Effects of Oral Lactobacillus on Pain Severity in Women Suffering from Endometriosis: A Pilot Placebo-Controlled Randomized Clinical Trial. Int J Fertil Steril. 2019;13(3):178-183. doi: 10.22074/ijfs.2019.5584. 
  17. Merra G, Noce A, Marrone G, Cintoni M, Tarsitano MG, Capacci A, De Lorenzo A. Influence of Mediterranean Diet on Human Gut Microbiota. Nutrients. 2020;13(1):7. doi: 10.3390/nu13010007.