Infertility, IL-17, IL-33 and Microbiome Cross-Talk: The Extended ARIA-MeDALL Hypothesis

Infertility, defined as the inability to obtain pregnancy after 12 months of regular unprotected sexual intercourse, has increased in prevalence over the past decades, similarly to chronic, allergic, autoimmune, or neurodegenerative diseases. A recent ARIA-MeDALL hypothesis has proposed that all these diseases are linked to dysbiosis and to some cytokines such as interleukin 17 (IL-17) and interleukin 33 (IL-33). Our paper suggests that endometriosis, a leading cause of infertility, is linked to endometrial dysbiosis and two key cytokines, IL-17 and IL-33, which interact with intestinal dysbiosis. Intestinal dysbiosis contributes to elevated estrogen levels, a primary factor in endometriosis. Estrogens strongly activate IL-17 and IL-33, supporting the existence of a gut-endometrial axis as a significant contributor to infertility.