复发性流产患者生殖道菌群特征的初步研究

doi:10.12280/gjszjk.20220153

摘要/Abstract

摘要：

目的：分析和比较正常早孕女性和复发性流产（recurrent spontaneous abortion,RSA）患者的生殖道菌群特征。方法：选取2021年3—9月在我院拟行清宫术的37例RSA患者为RSA组,同期拟行人工流产术的25例正常早孕女性为正常早孕组。对其阴道分泌物及子宫蜕膜组织进行16S rRNA测序,比较2组阴道和宫腔菌群的特征及差异。结果：与正常早孕女性相比,RSA患者阴道菌群多样性显著增多（P<0.05）,个体间菌群结构相似度较低,但优势菌未改变,仍为乳杆菌属,而乳杆菌属丰度显著降低（P<0.05）,且加德纳菌属、普雷沃菌属、巨型球菌属、李斯特菌属和厌氧球菌属丰度显著增加（P<0.05）;RSA患者宫腔菌群多样性及个体间菌群结构相似度无显著变化（P>0.05）,但优势菌种发生改变,正常早孕女性宫腔优势菌种为卷曲乳杆菌,RSA患者宫腔优势菌种为惰性乳杆菌,RSA患者宫腔菌群中两歧双歧杆菌和不能培养的不动杆菌丰度显著减少（P<0.05）,而拟杆菌属、大肠埃希菌/志贺菌属和瘤胃菌属团显著增加（P<0.05）。结论：正常的阴道和宫腔存在微生物菌群,宫腔比阴道的菌群多样性更高,但宫腔优势菌丰度较低。阴道细菌的上行定植可能与宫腔菌群的形成存在一定的相关性。而宫腔特有菌群的存在,尤其是宫腔优势菌种的改变和致病菌的出现,可能与RSA的发生相关。

关键词: 流产,习惯性, 生殖道感染, 微生物群落, 阴道, 子宫

Abstract:

Objective: To test the reproductive tract flora in patients with recurrent spontaneous abortion (RSA) and normal early pregnan women. Methods: From March 2021 to September 2021, 37 RSA patients who planned uterine cleaning in our hospital were selected as the RSA group, and 25 normal early pregnant women who planned artificial abortion as the normal early pregnant group. Bacterial 16S rRNAs in the vaginal secretions and uterine decidua tissues were tested by high-throughput sequencing. The characteristics of vaginal and uterine flora were compared between the two groups. Results: The diversity of vaginal flora was significantly increased, and the structural similarity of the flora among individuals was low in the RSA group when compared with the normal early pregnant group (both P<0.05). However, the dominant bacteria remained in Lactobacillus, and the abundance of Lactobacillus was significantly decreased in the RSA group (both P<0.05). The abundances of Gardnerella, Prevotella, Megasphaera, Dialister and Anaerococcus in the vagina of RSA group was significantly higher than those of the normal early pregnant group (all P>0.05). There were no significant changes in the diversity of uterine flora and the structural similarity of uterine flora among the individuals of the RSA group (P>0.05). However, the dominant bacteria was changed. The dominant bacteria was Lactobacillus_crispatus in the normal early pregnant group, while it was Lactobacillus_iners in the RSA group. The abundance of Bifidobacterium_bifidum and uncultured_Acinetobacter_sp decreased significantly in the uterine flora of RSA group (P<0.05), while the abundance of Bacteroides, Escherichia_Shigella and Ruminococcus_torques_group increased significantly (P<0.05). Conclusions: The vaginal and uterine microflora can be tested. The bacterial diversity of uterus was higher than that of vagina, but the abundance of dominant bacteria in the uterus was lower. The upward colonization of vaginal bacteria may be related to the formation of uterine flora. The specific bacterial flora in uterus, especially the change of dominant bacteria and the emergence of pathogenic bacteria, may be related to the occurrence of RSA.

Key words: Abortion,habitual, Reproductive tract infections, Microbial consortia, Vagina, Uterus

蔺凯丽, 郭洁, 任姝晴, 宋殿荣, 张继雯, 赵琳, 鲁娣, 王润景. 复发性流产患者生殖道菌群特征的初步研究[J]. 国际生殖健康/计划生育, 2022, 41(3): 177-183.

LIN Kai-li, GUO Jie, REN Shu-qing, SONG Dian-rong, ZHANG Ji-wen, ZHAO Lin, LU Di, WANG Run-jing. A Preliminary Study on the Characteristics of Reproductive Tract Flora in Patients with Recurrent Spontaneous Abortion[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(3): 177-183.

图/表 16

参考文献 18

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组别	n	年龄（岁）	BMI（kg/m²）	停经时间（d）	孕囊直径（cm）	孕次（次）	产次（次）
正常早孕组	25	29.60±3.75	21.93±0.88	53.72±3.75	2.23±0.63	2.92±0.86	1（0,1）
RSA组	37	30.81±3.53	22.21±1.07	55.24±3.83	2.44±0.91	3.16±0.75	0（0,1）
t或z		1.292	1.093	1.526	1.005	1.162	1.762
P		0.201	0.279	0.132	0.319	0.250	0.078

组别	n	年龄（岁）	BMI（kg/m²）	停经时间（d）	孕囊直径（cm）	孕次（次）	产次（次）
正常早孕组	25	29.60±3.75	21.93±0.88	53.72±3.75	2.23±0.63	2.92±0.86	1（0,1）
RSA组	37	30.81±3.53	22.21±1.07	55.24±3.83	2.44±0.91	3.16±0.75	0（0,1）
t或z		1.292	1.093	1.526	1.005	1.162	1.762
P		0.201	0.279	0.132	0.319	0.250	0.078

组别样本来源		有效序列（条）	Features（个）	门（种）	纲（种）	目（种）	科（种）	属（种）	种（种）
正常早孕组	阴道	1 988 319	670	21	36	69	117	221	303
	宫腔	1 792 935	5 055	37	101	233	377	799	1 173
RSA组	阴道	2 789 083	1 791	23	42	80	144	350	526
	宫腔	2 703 617	6 398	33	88	209	360	776	1 612

组别样本来源		有效序列（条）	Features（个）	门（种）	纲（种）	目（种）	科（种）	属（种）	种（种）
正常早孕组	阴道	1 988 319	670	21	36	69	117	221	303
	宫腔	1 792 935	5 055	37	101	233	377	799	1 173
RSA组	阴道	2 789 083	1 791	23	42	80	144	350	526
	宫腔	2 703 617	6 398	33	88	209	360	776	1 612

组别	样本来源	n	Observed	Chao 1	Shannon	Good’s Coverage
正常早孕组	阴道	25	45.00（38.00,65.50）	48.56（43.07,67.04）	0.65（0.19,1.48）	1.00
	宫腔	25	166.00（104.50,236.50）	171.67（107.28,237.34）	4.30（3.08,6.19）	1.00
	Z（P）		5.366（0.000）	5.229（0.000）	5.899（0.000）	-
RSA组	阴道	37	95.00（68.50,117.50）	99.07（72.22,140.45）	1.08（0.56,1.85）	1.00
	宫腔	37	134.00（104.00,217.50）	143.00（109.80,234.47）	5.48（3.57,5.96）	1.00
	Z（P）		3.514（0.000）	3.049（0.002）	6.508（0.000）	-