# Gut Microbiota as an Endocrine Organ: Unveiling Its Role in Human Physiology and Health
## 4 Gut Microbiota Metabolites and Hormonal Alterations in Human Physiology
### The Influence of the Gut Microbiota on the Endocrine Systems Related to Reproduction and Metabolism  
Expanding upon prior discussions in this article, we acknowledge the gut microbiota as a comprehensive endocrine organ, exerting influence over distant organs and pathways. Its significant role in the female reproductive endocrine system, interacting with oestrogens, androgens, insulin, and other hormones, is crucial throughout a woman's life [141]. Imbalances of the gut microbiota composition link to various conditions, including pregnancy complications, adverse outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer. Sex hormones such as oestradiol, testosterone, and progesterone play essential roles in communication between microorganisms and hosts [142], affecting various physiological functions. The human microbiome profoundly impacts all stages of female reproduction, from ovary maturation to pregnancy and parturition. Abnormal microbiomes, particularly in the gut, can adversely affect the reproductive endocrine system, emphasising the potential for improved reproductive outcomes through microbiome correction [143]. Several studies report linear correlations between gut microbiota and serum hormone levels, introducing the concept of the \"microgenderome\" [144]. Specific intestinal bacteria may also link to female diseases like PCOS, endometriosis, and bacterial vagnosis. The gut microbiota is intricately intertwined with oestrogen regulation, serving as both an influencer and recipient of estrogenic effects. Oestrogens, crucial gut microbiome regulators, prompt the identification of the 'estrobolome' [145], the microbial gene repertoire responsible for oestrogen metabolism. Fluctuations in oestrogen receptor \(\beta\) (ER\(\beta\)) expression and steroidal hormone concentrations underscore oestrogen's pivotal role throughout a woman's life. Microbially secreted \(\beta\)-glucuronidase plays a central role in metabolising oestrogens and influencing their circulating forms [146]. Dysbiosis and reduced microbiota diversity diminish \(\beta\)-glucuronidase activity, impacting oestrogen deconjugation and potentially leading to hypoestrogenic pathologies like obesity, metabolic syndrome, cardiovascular diseases, and cognitive decline. Conversely, an abundance of \(\beta\)-glucuronidase-producing bacteria may elevate circulating oestrogen levels, contributing to diseases such as endometriosis and cancer. Oestrogen's influence extends to conditions like PCOS, endometrial hyperplasia, and fertility [147]. Murine ER\(\beta\) status links steroid nuclear receptors and dietary complexity to gut microbiota composition. A negative correlation between microbiota alpha diversity and oestradiol concentrations suggests bidirectional gut microbe-sex hormone interactions. Recent insights reveal the gut microbiome's role in 17\(\beta\)-oestradiol's preventive effects against metabolic endotoxemia and chronic inflammation [147]. Altered microbial profiles in oestrogen-treated male and ovariectomized female mice resemble normal females, emphasising oestrogen's role in mitigating LPS production and improving gut barrier integrity. Oestrogen's association with sex hormone-driven cancers underscores altered gut microbiota compositions in these conditions [148]. High-fat-diet-associated steroids may influence the gastrointestinal microbiome, affecting carcinogenesis. Decreased oestrogen metabolite ratios and reduced faecal microbiota diversity correlate with an elevated risk of breast cancer in postmenopausal women [149]. Postmenopausal gut microbiota diversity positively associates with oestrogen metabolite ratios in urine, impacting factors like insulin resistance and type 2 diabetes development. The gut microbiota's capacity to metabolise oestrogen-like compounds in foods, such as soy isoflavones, influences specific bacterial growth. _Bifidobacterium_'s beneficial role contrasts with the inflammatory associations and obesity linkage of _Clostridiaceae_[150].