Estrobolome in the Gut–Vagina Axis: A Microbial Endocrinology Perspective

The estrobolome, defined as the collection of gut microbial genes encoding enzymes that metabolize estrogens and, by extension, the taxa that harbor them, has emerged as a central node of the new concept of “microbial endocrinology” within the gut–vagina axis. By regulating enterohepatic recirculation of conjugated estrogens, the estrobolome may modulate systemic estrogen availability and thereby may influence the estrogen-dependent biology of gynecological organs and tissues, including ovaries, endometrium, and the vaginal mucosa with its Lactobacillus-dominated ecosystem. In this narrative review, we synthesize current evidence on how gut microbial β-glucuronidases, sulfatases, and related enzymes shape circulating estrogen pools and, in turn, gynecological health. We outline the enzymatic and taxonomic architecture of the estrobolome, describe its major ecological determinants, and integrate these with mechanisms of the gut–vagina axis. We then examine how estrobolome function varies across a woman’s lifespan and how these dynamics intersect with vaginal health, dysbiosis, and conditions such as recurrent vaginitis, endometriosis, and polycystic ovary syndrome. We also review emerging strategies that may modulate the estrobolome as a microbial endocrine organ and discuss their potential downstream effects on gynecological health. Finally, we highlight major research gaps, particularly the need for causal, longitudinal, multi-omics studies explicitly linking estrobolome activity, systemic estrogens, and gynecological outcomes. Overall, available data support a mechanistically plausible but incompletely defined role for the estrobolome as a key microbial endocrine player in the gut–vagina axis and point toward microbiome-informed strategies to preserve and restore gynecological health across a woman’s lifespan.