Tempol ameliorates polycystic ovary syndrome through attenuating intestinal oxidative stress and modulating of gut microbiota composition-serum metabolites interaction

Feb 16, 2021Redox biology

Tempol may improve polycystic ovary syndrome by reducing gut oxidative stress and changing gut bacteria and blood metabolites

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Abstract

Tempol treatment in PCOS rats resulted in improved ovarian dysfunction and glucose tolerance.

Tempol reduced intestinal oxidative stress in PCOS rats without impacting ovarian redox rate.
Significant differences in gut microbiota composition and serum metabolite profiles were observed between control and PCOS rats, with many differences diminished after tempol treatment.
Tempol increased the abundance of the beneficial gut bacteria genus Ruminococcus_1 while decreasing several other genera.
Serum levels of bile acid and stachyose were restored in PCOS rats following tempol treatment, with stachyose levels correlating significantly with the abundance of 15 gut genera.
Administration of stachyose improved ovarian dysfunction in the PCOS rat model.

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Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, which is often accompanied by oxidative stress. Tempol, a superoxide dismutase mimetic, protects against several diseases caused by oxidative stress. However, the effect of tempol on PCOS has not been investigated. The present study demonstrated the alleviation of ovarian dysfunction and glucose tolerance in dehydroepiandrosterone (DHEA)-induced PCOS rats treated with tempol. Tempol significantly reduced the intestinal oxidative stress in PCOS rats without affecting the ovarian redox rate. The 16S rDNA sequencing of the intestinal microbiome and non-targeted metabolomics analysis indicated significant differences in gut microbiota composition and serum metabolite profiles between the control and PCOS rats, and most of these differences were reduced after tempol intervention. Tempol alters the gut microbiome by increasing the abundance of genus Ruminococcus_1 and by decreasing the abundance of Ruminococcus_2, Staphylococcus, Ideonella, and Corynebnacterium genera. Tempol also attenuates the reduction of serum bile acid and stachyose levels in PCOS rats, and the serum stachyose level was significantly correlated with the abundance of 15 genera, particularly Ruminococcus_1 and Ruminococcus_2. Moreover, stachyose administration improved ovarian dysfunction in PCOS rats. Thus, our data indicate that tempol ameliorates PCOS phenotype by reducing intestinal oxidative stress, restoring gut dysbiosis, and modulating the interaction between gut microbiota and host metabolite. Therefore, tempol intervention is a potential therapeutic approach for PCOS.

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Tempol ameliorates polycystic ovary syndrome through attenuating intestinal oxidative stress and modulating of gut microbiota composition-serum metabolites interaction

Abstract

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