ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2023, Vol. 32 ›› Issue (3): 231-237.DOI: 10.3969/j.issn.1006-298X.2023.03.006

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肾移植受者肠道菌群特征及其与糖代谢紊乱的关联

  

  • 出版日期:2023-06-28 发布日期:2023-07-01

Characteristics of intestinal flora in kidney transplant recipients and its relationship with glucose metabolism disorder

  • Online:2023-06-28 Published:2023-07-01

摘要: 目的:明确肾移植受者肠道菌群结构和代谢改变模式,评估差异菌群对肾移植后糖尿病(PTDM)的预测价值。
方法:纳入2001年1月至2022年7月在宁波大学附属李惠利医院手术及随访的肾移植受者,分为移植后高血糖(PTHG)组[包括PTDM组和移植后糖尿病前期(prePTDM)组]和血糖正常组,对其粪便标本进行16S rRNA基因V3-V4区域测序。比较PTHG组与血糖正常组粪便菌群结构及功能改变,分析差异菌群与临床理化指标之间的关联,并评估其辅助诊断PTHG的能力。
结果:纳入肾移植受者92例,其中PTHG组36例(包括PTDM组29例,prePTDM组7例)。与血糖正常组相比,PTHG患者粪便菌群丰度和多样性的增加无统计学意义。PTHG组中芽孢杆菌属(Gemmiger)和亚诺杆菌属(Anaerobacterium)的相对丰度显著增加,而黄杆菌属(Flavonifractor)、双歧杆菌属(Bifidobacterium)和副沙门氏菌属(Parasutterella)的相对丰度显著减少(P<0.05)。关联分析显示,芽孢杆菌属和 Anaerobacterium菌属与空腹血糖值呈显著正相关,而丹毒丝菌科的未命名属(Erysipelotrichaceae_incertae_sedis)与空腹血糖值呈显著负相关(相关系数>0.3且P<0.05)。联合上述6种菌属绘制ROC曲线(AUC=0.830),并将菌群联合空腹血糖进行分析(AUC=0.962),大于空腹血糖的单独诊断效能。PTHG组氨基糖、核苷酸糖和半乳糖代谢等糖代谢途径以及胆汁酸生物合成显著减少。亚组分析显示,脱硫弧菌属(Desulfovibrio)、Anaerobacterium菌属和芽孢杆菌属在PTDM、prePTDM和血糖正常三组间呈递减趋势,但趋势并不显著。
结论:PTDM患者肠道菌群结构和功能发生显著改变,差异菌群与糖代谢显著相关。部分菌群在PTDM、prePTDM和血糖正常三组间呈递减趋势。


关键词: 肠道微生物, 移植后糖尿病, 16S rRNA基因测序, 肾移植

Abstract: Objective:To investigate the constitute and metabolic changes of intestinal microflora in patients with posttransplantation diabetes mellitus (PTDM) after kidney transplantation, and to evaluate the predictive value of differential microflora in diabetes mellitus after kidney transplantation.
Methodology:Kidney transplant recipients who underwent surgery and follow-up in Lihuili Hospital affiliated to Ningbo University from January 2001 to July 2022 were divided into PTHG group [post-transplantation hyperglycemia, including PTDM group and posttransplantation prediabetes mellitus (prePTDM) group] and normal blood glucose group. Their fecal samples were sequenced by 16s rRNA gene V3-V4 region. The sonstitute and function of fecal microflora in PTHG group and normal blood glucose group were compared, the relationship between differential microflora and clinical physicochemical indexes was analyzed.
Results:92 renal transplant recipients were stuclied, including 36 cases in PTHG group (29 cases in PTDM group and 7 cases in prePTDM group). Compared with the group with normal blood glucose, the abundance and diversity of fecal microflora in patients with PTHG were not significantly changed (P>0.05). In PTHG group, the relative abundance of Gemmiger and Anaerobacterium increased significantly, while that of Flavobacterium, Bifidobacterium and Parasutterella decreased significantly (P<0.05). Correlation analysis showed that Gemmiger and Anaerobacterium had a significant positive correlation with fasting blood glucose, while Erysipelotrichaceae_incertae_sedis had a significant negative correlation with fasting blood glucose (correlation>0.3 and P<0.05). The ROC curve (AUC=0.830) was drawn with the above six bacteria, and the flora combined with fasting blood glucose was analyzed (AUC=0.962), which was higher than the diagnostic efficiency of fasting blood glucose alone. Carbohydrate metabolic pathways such as amino sugar, nucleoside sugar and galactose metabolism and bile acid biosynthesis were significantly decreased in PTHG group. Subgroup analysis showed that Desulfovibrio, Anaerobacterium and Gemmiger showed a decreasing trend among PTDM, prePTDM and Normal groups, but the trend was not significant.
Conclusion:The constitute and function of intestinal flora in patients with PTDM changed significantly, and the difference of microflora was significantly related to glucose metabolism. Some of the microflora showed a decreasing trend among PTDM, prePTDM and normal blood glucose groups.


Key words: intestinal microflora, post-transplantation diabetes mellitus, 16S rRNA gene sequencing, kidney transplantation