TABLE 1.

Studies linking natural hormones, the related diseases and the effects on the microbiota.

References	Animal model	Microbiota location	Dysbiosis/Related condition	Microbiota changes
Studies in animals
Yuan et al. (2018)	C57BL6 mice	Gut	• Endometriosis induced the dysbiosis.	• Increased Firmicutes/Bacteroidetes ratio. • Increased Bifidobacterium (phylum Actionobacteria).
Bailey and Coe (2002)	Female rhesus monkeys	Gut	• Endometriosis is associated with an altered profile of intestinal microbiota.	• Decreased Lactobacilli. • Increased Gram-negative aerobic and facultative anaerobic bacteria.
Markle et al. (2013)	Diabetic and non-obese diabetic mice	Gut	• Childhood T1D may induce dysbiosis.	• Commensal colonization resulted in increased serum levels of testosterone and protected non-obese diabetic males from T1D. • In young females, the transfer of gut microbiota from adult males resulted in microbiota changes, with increased testosterone and metabolic changes, decreased inflammation of pancreatic islets and autoantibody production, and protection against T1D.
Guo et al. (2016)	Female Sprague-Dawley rats with PCOS	Gut	• PCOS may significantly alter the gut microbiome.	• Decreased Lactobacillus, Ruminococcus, and Clostridium and increased Prevotella were found in PCOS females. For Bifidobacterium, Escherichia coli, Enterococcus, and Bacteroides there was no significant differences between PCOS females and the control group. • Gut dysbiosis was related to sex hormone levels, estrous cycles and morphological changes in the ovaries.
Kelley et al. (2016)	Female C57BL/6N mice with PCOS	Gut	• PCOS may significantly alter the gut microbiome.	• A significant decrease in the overall species composition and phylogenetic diversity of the gut microbiota, particularly in the relative abundance of Bacteroidetes and Firmicutes, was observed.
Studies in humans
Banerjee et al. (2017)	Women	Tumor ovarian tissue and non-tumor ovarian tissue	• Altered microbiome in ovarian tumor tissue.	• Increased Proteobacteria and Firmicutes. • Decreased Bacteroidetes, Actinobacteria, Chlamydiae, Fusobacteria, Spirochaetes and Tenericutes. • Retroviridae, Hepadnaviridae, Papillomaviridae, Flaviviridae, Polyomaviridae and Herpesviridae abound in > 50% of cancer samples. • Pneumocystis, Acremonium, Cladophialophora, Malassezia, and Microsporidia Pleistophora were significantly detected in all the ovarian cancer samples screened//in 100% of tumor samples examined.
Sfanos et al. (2018)	Men	Gut	• Prostate cancer hormonal therapy may alter the gut microbiota.	• Decreased alpha diversity in the gut microbiota of prostate cancer patients. • A significant increase in Akkermansia muciniphila, Ruminococcaceae spp., and Lachnospiraceae spp., was found in the fecal samples of prostate cancer patients undergoing oral ATT. Additionally, a significant decrease in the number of sequencing reads belonging to families such as Brevibacteriaceae, Erysipelotrichaceae, and Streptococcaceae was also observed.
Golombos et al. (2018)	Men	Gut	• An alteration of gut microbiota was observed in men with prostate cancer.	• Increased Bacteriodes massiliensis in prostate cancer patients versus controls. • Increased Faecalibacterium prausnitzii and Eubacterium rectale in controls versus prostate cancer patients.
Liu et al. (2017)	Women	Gut	• Disturbances in the gut microbiota of both obese and non-obese women with PCOS compared to non-obese controls.	• Decreased bacterial alpha diversity, increased LPS-producing bacteria, and decreased spore-forming bacteria species. • Increased Bacteroides and Escherichia/Shigella and decreased Akkermensia in obese women with PCOS.
Fuhrman et al. (2014)	Women	Gut	• Higher gut microbiota diversity was found in women with a high hydroxylated estrogens metabolites/parental estrogens ratio in urine.	• The relative abundances of the Clostridia class, including the Clostridiales order and the Ruminococcaceae family, were directly associated with the ratio of metabolites to parental estrogens, while the Bacteroides genus was inversely associated with this ratio.

T1D: type 1 diabetes; PCOS: polycystic ovary syndrome; ATT: axis-targeted therapies.