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阴道蔗糖凝胶应用诱导恒河猴阴道微生物群定向偏移。

Directed shift of vaginal microbiota induced by vaginal application of sucrose gel in rhesus macaques.

机构信息

Department of Infectious Diseases and Shenzhen key lab for endogenous infection, Shenzhen Nanshan Hospital, Guangdong Medical College. No 89, Taoyuan Road, Nanshan district, Shenzhen 518052, China.

Department of Infectious Diseases and Shenzhen key lab for endogenous infection, Shenzhen Nanshan Hospital, Guangdong Medical College. No 89, Taoyuan Road, Nanshan district, Shenzhen 518052, China.

出版信息

Int J Infect Dis. 2015 Apr;33:32-6. doi: 10.1016/j.ijid.2014.12.040. Epub 2014 Dec 26.

DOI:10.1016/j.ijid.2014.12.040
PMID:25546169
Abstract

OBJECTIVES

Sucrose gel was used to treat bacterial vaginosis in a phase III clinical trial. However, the changes of vaginal flora after treatment were only examined by Nugent score in that clinical trial, While the vaginal microbiota of rhesus macaques is characterized by anaerobic, Gram-negative bacteria, few lactobacilli, and pH levels above 4.6, similar to the microbiota of patients with bacterial vaginosis. This study is aimed to investigate the change of the vaginal microbiota of rehsus macaques after topical use of sucrose gel to reveal more precisely the bacterial population shift after the topical application of sucrose gel.

METHODS

Sixteen rhesus macaques were treated with 0.5 g sucrose gel vaginally and three with 0.5 g of placebo gel. Vaginal swabs were collected daily following treatment. Vaginal pH levels and Nugent scores were recorded. The composition of the vaginal micotbiota was tested by V3∼V4 16S rDNA metagenomic sequencing. Dynamic changes in the Lactobacillus genus were analyzed by qPCR.

RESULTS

The vaginal microbiota of rhesus macaques are dominated by anaerobic Gram-negative bacteria, with few lactobacilli and high pH levels above 4.6. After five days' treatment with topical sucrose gel, the component percentage of Lactobacillus in vaginal microbiota increased from 1.31% to 81.59%, while the component percentage of Porphyromonas decreased from 18.60% to 0.43%, Sneathia decreased from 15.09% to 0.89%, Mobiluncus decreased from 8.23% to 0.12%, etc.. The average vaginal pH values of 16 rhesus macaques of the sucrose gel group decreased from 5.4 to 3.89. There were no significant changes in microbiota and vaginal pH observed in the placebo group.

CONCLUSIONS

Rhesus macaques can be used as animal models of bacterial vaginosis to develop drugs and test treatment efficacy. Furthermore, the topical application of sucrose gel induced the shifting of vaginal flora of rhesus macaques from a BV kind of flora to a lactobacilli-dominating flora.

摘要

目的

蔗糖凝胶曾被用于一项 III 期临床试验中治疗细菌性阴道病。然而,该临床试验仅通过 Nugent 评分来检测治疗后阴道菌群的变化,而恒河猴的阴道微生物群以厌氧、革兰氏阴性菌为主,几乎没有乳杆菌,pH 值高于 4.6,与细菌性阴道病患者的微生物群相似。本研究旨在探讨恒河猴阴道菌群在局部使用蔗糖凝胶后的变化,以更准确地揭示蔗糖凝胶局部应用后细菌种群的变化。

方法

16 只恒河猴阴道内给予 0.5g 蔗糖凝胶,3 只阴道内给予 0.5g 安慰剂凝胶。治疗后每天采集阴道拭子。记录阴道 pH 值和 Nugent 评分。通过 V3-V4 16S rDNA 宏基因组测序检测阴道微生物群的组成。通过 qPCR 分析乳杆菌属的动态变化。

结果

恒河猴阴道微生物群以厌氧革兰氏阴性菌为主,乳杆菌较少,pH 值高于 4.6。局部应用蔗糖凝胶治疗 5 天后,阴道微生物群中乳杆菌的组成百分比从 1.31%增加到 81.59%,而普雷沃菌的组成百分比从 18.60%降至 0.43%,Sneathia 从 15.09%降至 0.89%,Mobiluncus 从 8.23%降至 0.12%等。蔗糖凝胶组 16 只恒河猴的平均阴道 pH 值从 5.4 降至 3.89。安慰剂组的微生物群和阴道 pH 值没有明显变化。

结论

恒河猴可作为细菌性阴道病的动物模型用于开发药物和测试治疗效果。此外,蔗糖凝胶的局部应用诱导恒河猴阴道菌群从 BV 样菌群转变为以乳杆菌为主的菌群。

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