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Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic
Dysregulation in a PCOS Mouse Model.

Authors	Torres PJ, Ho BS, Arroyo P, Sau L, Chen A, Kelley ST, Thackray VG
Submitted By	Submitted Externally on 3/31/2020
Status	Published
Journal	Endocrinology
Year	2019
Date Published	5/1/2019
Volume : Pages	160 : 1193 - 1204
PubMed Reference	30924862
Abstract	Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting ~10% to 15% of reproductive-aged women worldwide. Diagnosis requires two of the following: hyperandrogenism, oligo-ovulation or anovulation, and polycystic ovaries. In addition to reproductive dysfunction, many women with PCOS display metabolic abnormalities associated with hyperandrogenism. Recent studies have reported that the gut microbiome is altered in women with PCOS and rodent models of the disorder. However, it is unknown whether the gut microbiome plays a causal role in the development and pathology of PCOS. Given its potential role, we hypothesized that exposure to a healthy gut microbiome would protect against development of PCOS. A cohousing study was performed using a letrozole-induced PCOS mouse model that recapitulates many reproductive and metabolic characteristics of PCOS. Because mice are coprophagic, cohousing results in repeated, noninvasive inoculation of gut microbes in cohoused mice via the fecal-oral route. In contrast to letrozole-treated mice housed together, letrozole mice cohoused with placebo mice showed significant improvement in both reproductive and metabolic PCOS phenotypes. Using 16S rRNA gene sequencing, we also observed that the overall composition of the gut microbiome and the relative abundance of Coprobacillus and Lactobacillus differed in letrozole-treated mice cohoused with placebo mice compared with letrozole mice housed together. These results suggest that dysbiosis of the gut microbiome may play a causal role in PCOS and that modulation of the gut microbiome may be a potential treatment option for PCOS.

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