Effect of various types of gut microbiota in patients on the diminished ovarian reserve

Abstract Background Diminished ovarian reserve (DOR) is a type of reproductive endocrine disease associated with infertility and premature menopause due to the decline in the number and quality of oocytes. In recent years, studies have been conducted on the relationship between gut microbiota and reproductive health, our objective was to find a solid relationship between gut microbiota and DOR. Methods After rigorous inclusion criteria, 34 women with DOR and 30 normal ovarian reserve controls were recruited at the Reproductive Medical Center of Shengjing Hospital of China Medical University from March to December 2021. Serum levels of AMH, basal sex hormones, AFC, gut microbiota and short-chain fatty acids were measured in two groups. Results Quantitative polymerase chain reaction (qPCR) sequencing technology and gas chromatography was introduced to find a significant difference of the composition and metabolites of gut microbiota between DOR and healthy individuals. After careful comparison of Prevotella/Bacteroides frequencies, we found that individuals with Prevotella /Bacteroides > 0.01 had a higher possibility with DOR. In addition, receiver operating characteristic and spearman correlation analysis were applied to identify butyrate and isobutyrate as a mark to predict the risk of DOR. After canonical correlation analysis, we found that in patients with Prevotella enterotype, Akkermansia muciniphila and Enterobacteria could be considered as harmful bacteria. Based on the above results, an intervention was conducted on six patients who suffered from DOR. After 28 day intervention, the concentration of Enterobacteria and isobutyrate were significantly reduced, meanwhile the amounts of Bifidobacteria were significantly increased. Finally, the concentrations of antral follicle count (AFC) were increased and two thirds of them were successfully pregnant. Conclusions In summary, we defined population with Prevotella/Bacteroides > 0.01 as Prevotella enterotype and found that Prevotella enterotype was closely related to DOR. Akkermansia muciniphila, Enterobacteria, Bifidobacteria, butyrate, and isobutyrate could be used as biomarkers to predict the ovarian reserve in two enterotypes. And different dietary interventions for two enterotypes and have demonstrated significant clinical effects.