Association Study Of Short-chain Fatty Acids And Diminished Ovarian Reserve Based On Enterotype

Objective: Gut dysbiosis has been confirmed to be related to reproductive endocrine disorders,but its relationship to diminished ovarian reserve(DOR)remains unclear.The objective of this study was to investigate the relationship between DOR and gut microbiota with its metabolites in populations with different enterotypes.Methods: We recruited 46 women with DOR and 55 women with normal ovarian reserve(NOR)from the Reproductive Medical Center of Shengjing hospital of China Medical University.We recorded clinical indexes of the included participants.Quantitative polymerase chain reaction was used to determine bacterial counts(Bacteroides,Prevotella,Bifidobacterium,Lactobacillus,Roseburia,Akkermansia muciniphila and Faecalibacterium prausnitzii)in fecal samples.Gas chromatography was used to determine the concentrations of short-chain fatty acids(SCFAs).Results: In Prevotella-enterotype participants(Prevotella/Bacteroides,P/B ≥ 0.01),isovaleric acid was identified as a risk factor for DOR(OR: 1.883;95% CI: 1.025–3.460;P = 0.04),Bifidobacterium(P < 0.05)and Lactobacillus(P < 0.05)were negatively correlated with DOR.In Bacteroides-enterotype participants(P/B < 0.01),acetic acid was identified as a risk factor for DOR(OR: 1.063;95% CI: 1.013–1.116;P = 0.01),Bifidobacterium(P < 0.01)and Lactobacillus(P < 0.05)were positively correlated with DOR.Receiver operating characteristic curve analysis demonstrated that the combination of SCFAs and gut microbiota had superior predictive effect on DOR.In Prevotella-enterotype participants,the sensitivity and specificity for DOR prediction were 53.3% and 90.0% by the combination of isovaleric acid,Bifidobacterium and Lactobacillus,with the area under the curve(AUC)of 74.0%.Likewise,the sensitivity and specificity for DOR prediction were 87.5% and 76.0% by the combination of acetic acid,Bifidobacterium and Lactobacillus,producing an AUC of 83.3% in Bacteroides-enterotype participants.Conclusion: Our study identified a close relationship between gut microbiota and DOR.Fecal concentrations of SCFAs can be used as a non-invasive screening tool for DOR.Furthermore,the combination of SCFAs concentrations and disease-related bacteria counts could be used to identify individuals with a high risk of developing DOR in different enterotypes.Data in this presenting study suggest that customizing the individualized diets to regulate the gut microbiota should be undertaken as early as possible.