肥胖与非肥胖PCOS患者的肠道微生物群结构及代谢功能的关系

Correlation between gut microbiota composition and metabolic functions in obese and non-obese patients with polycstie ovary syndrome

目的比较肥胖和非肥胖多囊卵巢综合征(PCOS)患者的肠道微生物群特征及代谢功能。方法选取2020年6月至2022年6月就诊的16例肥胖PCOS女性(BMI≥28 kg/m^(2),肥胖PCOS组),12例非肥胖PCOS女性(BMI为18.5~23.9 kg/m^(2),非肥胖COS组)和14例健康年轻女性(BMI 18.5~23.9 kg/m^(2),非肥胖正常组),以及6例健康但肥胖女性(BMI≥28 kg/m^(2))作为肥胖正常组。收集并分析所有参与者的血液和非经期粪便样本。通过对原核16S rDNA基因进行测序来分析粪便样本。通过液相色谱-串联质谱法进行血浆代谢组学分析。结果与非肥胖正常组相比,非肥胖PCOS组中多毛症评分、痤疮评分、黄体生成素(LH)、LH/卵泡刺激素(FSH)、睾酮、E_(2)和脱氢表雄酮显著增加(P<0.05)。与肥胖正常组相比,肥胖PCOS组中多毛评分、LH/FSH和睾酮显著升高(P<0.05),FSH显著降低(P<0.05)。差异丰度分析确定了与肥胖状态显著相关的4个属(Finegoldia、Anaerococcus、Sneathia和Adlercreutzia)(P<0.05)。与没有肥胖的女性相比,Finegoldia、Anaerococcus、Sneathia、Adlercreutzia在肥胖女性中的丰度显著较低(P<0.05)。在按PCOS状态分层的分析中,Finegoldia和Anaerococcus在PCOS和非PCOS女性中均与肥胖呈显著负相关,而PCOS和肥胖与Sneathia和Adlercreutzia之间存在暗示性但不显著的相互作用(分别为PPCOS×肥胖=0.090、0.057)。Anaerococcus与犬尿氨酸/色氨酸比率和缬氨酸呈负相关(r=-0.38、-0.30,P=0.007、0.041),而Adlercreutzia与脯氨酸和丙氨酸呈负相关(r=-0.37、-0.32,P=0.012、0.034)。结论在PCOS女性中,肥胖与肠道微生物群和血浆代谢物的改变有关,包括产生丁酸盐的细菌群的消耗以及更高的色氨酸分解代谢。这些发现表明肠道菌群、肥胖与PCOS之间存在潜在的相互关系。

Objective To compare the characteristics of gut microbiota and metabolic functions in patients with polycystic ovary syndrome(PCOS),specifically focusing on the differences between obese and non-obese individuals.Methods Sixteen obese PCOS females(BMI≥28 kg/m^(2)),twelve non-obese PCOS females(BMI 18.5-23.9 kg/m^(2)),and fourteen healthy young females(BMI 18.5-23.9 kg/m^(2))were selected from June 2020 to June 2022 as the non-obese normal group.Additionally,six healthy but obese females(BMI≥28 kg/m^(2))were included as the obese normal group.Blood and non-menstrual fecal samples were collected and analyzed from all participants.Fecal samples were sequenced using 16S rDNA gene sequencing.Plasma metabolomics analysis was performed using liquid chromatogra-phy-tandem mass spectrometry.Results Compared to the non-obese normal group,non-obese PCOS showed signifi-cant increases in hirsutism scores,acne scores,LH,LH/FSH,testosterone,E2,and dehydroepiandrosterone(P<0.05).In comparison to the obese normal group,obese PCOS exhibited significantly higher hirsutism scores,LH/FSH,and testosterone,along with significantly lower FSH(P<0.05).Differential abundance analysis identified four genera(Finegoldia,Anaerococcus,Sneathia,and Adlercreutzia)significantly associated with obesity status(P<0.05).Fine-goldia,Anaerococcus,Sneathia,and Adlercreutzia showed significantly lower abundance in obese females compared to non-obese females(P<0.05).Stratified analysis based on PCOS status revealed a significant negative correlation between Finegoldia and Anaerococcus with obesity in both PCOS and non-PCOS females.There were suggestive but not significant interactions between PCOS and obesity with Sneathia and Adlercreutzia(Ppcos xohesiy=0.090,0.057).Anaerococcus exhibited a negative correlation with the ratio of indole-3-acetic acid to tryptophan and valine(r=-0.38,-0.30,P=0.007,0.041),while Adlercreutzia showed a negative correlation with proline and alanine(r=-0.37,-0.32,P=0.012,0.034).Conclusion In PCOS females,obesity is associated with changes in gut microbiota and plasma metabolites,including the depletion of bacteria producing butyrate and increased tryptophan degradation metabolism.These findings suggest potential interrelationships among gut microbiota,obesity,and PCOS.