# 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
The host-microbe oestrogen interaction spans diverse pathways affecting women's health, including fertility, obesity, diabetes, and cancer. A deeper understanding of these interactions holds the potential for innovative approaches to mitigate endocrine disease risks in women. Hyperandrogenaemia (HA) is a prominent characteristic of polycystic ovary syndrome (PCOS) [151], contributing significantly to manifestations such as hirsutism, acne, male pattern alopecia, and anvulation. In PCOS, elevated luteinism hormone (LH) prompts excess androgen production by ovarian theca cells, coupled with low follicle-stimulating hormone (FSH), leading to impaired folliculogenesis and anvulation, a common cause of infertility [152]. The repercussions of HA extend to increased risks of insulin resistance, type 2 diabetes, hypertension, obesity, and cardiovascular disease. Testosterone, a key androgen, influences the gut microbiome composition in females. Analysis in PCOS mice revealed a correlation between reduced abundances of specific genera, higher circulating testosterone levels, and impaired glucose metabolism [151]. Microbiota removal impacts circulating testosterone concentrations bidirectionally between female and male mice, suggesting a reciprocal relationship between male sex hormone levels and the microbiota [153]. Prenatal androgen (PNA) exposure leaves a lasting impact on the developing female foetus, increasing the likelihood of PCOS diagnosis in daughters. Transgenerational effects manifest in reproductive and metabolic dysfunctions mediated by in utero and oocyte-derived factors [154]. In a dihydrotestosterone (DHT)-induced mouse model, _Anaroococcus_'s relative abundance correlates positively with testosterone levels in the high androgen group. The gut microbiota and its metabolites activate pathways leading to abnormal fat accumulation, insulin resistance, and compensatory hyperinsulinemia. A testosterone propionate-induced mouse model revealed it altered faecal microbiota profiles in PNA animals, including increased bacteria associated with steroid hormone synthesis and short-chain fatty acid production. These mice experienced an impact on cardiovascular function, suggesting long-term effects on gut microbiota and cardiometabolic function [155]. _Ruminococcus_ significantly increases in neonatally androgenised rats, correlating with elevated serum testosterone levels. Studies indicate a negative correlation between alpha diversity and total testosterone, hyperandrogenism, and hirsutism. Animal models of PNA exposure and maternal HA show increased bacteria associated with steroid synthesis and SCFA elongation, with decreased _Akkermansia_, _Bacteroides_, _Lactobacillus_, and _Clostridium_. These models exhibit increased body weight, altered adipokine mRNA expression, and negatively impacted cardiovascular function [156]. Conversely, studies by [PERSON] and [PERSON] et al. [157] demonstrate a positive correlation between gut microbiota alpha diversity and testosterone levels, suggesting a role in sex hormone regulation and potential modification of microbial diversity. However, limitations in these studies call for a more in-depth assessment of the mechanistic basis for gut microbiota and androgen interaction. Various gut microbiota express enzymes involved in androgen metabolism, contributing to the synthesis and transformation of androgens. Microbial processes, including those by _Actinobacteria_ and _Proteobacteria_, observe testosterone degradation. _Clostridium scindens_, a human gut microbe, encodes 20\(\alpha\)-hydroxysteroid dehydrogenase (HSDH), showing potential for converting glucocorticoids into androgens [157]. In conclusion, excess androgens can induce dysbiosis in the host gut microbiota, influencing the development and pathology of women's endocrine systems, particularly in PCOS. Future research should investigate mechanistic details to establish a comprehensive theoretical foundation and therapeutic targets for Hyperandrogenaemia (HA) diagnosis and treatment.