抗逆转录病毒治疗对HIV感染者血液微生物组的影响分析

doi:10.19586/j.2095-2341.2025.0060

生物技术进展 ›› 2025, Vol. 15 ›› Issue (5): 921-929.DOI: 10.19586/j.2095-2341.2025.0060

• 研究论文 • 上一篇

抗逆转录病毒治疗对HIV感染者血液微生物组的影响分析

赵靖悦(), 温娟, 张荣秋, 张建梅()

厦门市疾病预防控制中心，福建厦门 361021

收稿日期:2025-05-12 接受日期:2025-08-18 出版日期:2025-09-25 发布日期:2025-11-11
通讯作者: 张建梅
作者简介:赵靖悦 E-mail: 409834984@qq.com；
基金资助:
福建省卫生健康科技计划项目(2022GGB014)

The Effect of Antiretroviral Therapy on the Blood Microbiome in HIV-infected Individuals

Jingyue ZHAO(), Juan WEN, Rongqiu ZHANG, Jianmei ZHANG()

Disease Prevention and Control Center of Xiamen，Fujian Xiamen 361021，China

Received:2025-05-12 Accepted:2025-08-18 Online:2025-09-25 Published:2025-11-11
Contact: Jianmei ZHANG

摘要/Abstract

摘要：

研究抗逆转录病毒治疗(antiretroviral therapy，ART)对HIV感染者血液中微生物菌落组成的影响。收集28例ART治疗的HIV感染者（ART组）和30例未治疗的HIV感染者（naive组），利用宏基因测序分析血液微生物菌群的物种组成差异。宏基因测序后共获得2 001 686条有效序列，经物种注释获得9个门、17个纲、35个目、55个科、84个属和141个种水平的物种。ART组的丰富度（Chao1指数）和多样性（Simpson指数和Shannon指数）显著高于naive组。黄单胞菌属、有益杆菌属、施蒂泽氏单胞菌属、普罗威登斯菌属、另类弓形菌属、表皮杆状菌属、肠球菌属和栖热菌属在ART组显著富集，假单胞菌属、固氮螺菌属、埃希氏菌属、不动杆菌属、寡养单胞菌属在naive组显著富集。进一步线性判别效应量分析（linear discriminant analysis effect size，LEfSe）发现ART组有6个物种，而naive组有5个物种存在显著性差异。综上，治疗后HIV感染者的血液中菌群微生物丰富度和多样性显著改善，治疗与未治疗的HIV感染者血液微生物在门水平和属水平的优势物种存在较大差异，且ART治疗可能减少血液中致病性细菌。研究结果可为血液微生物群与HIV进展间的相互作用提供新的见解，特定的微生物物种可作为评价HIV治疗效果的潜在指标，并为诊断和制定治疗策略提供依据。

关键词: 人免疫缺陷病毒, 抗逆转录病毒治疗, 宏基因组, 血液微生物组

Abstract:

To investigate the impact of antiretroviral therapy （ART） on the composition of microbial flora in the blood of HIV-infected individuals. Blood samples were collected from 28 ART-treated HIV-infected patients （ART group） and 30 untreated HIV-infected patients （naive group）. Metagenomic sequencing was performed to analyze differences in the composition of blood microbial communities. After metagenomic sequencing，a total of 2 001 686 valid sequences were obtained. Taxonomic annotation identified microbial species at 9 phyla，17 classes，35 orders，55 families，84 genera， and 141 species levels. The richness （Chao1 index） and diversity （Simpson index and Shannon index） of the ART group were significantly higher than those of the naive group. Genera such as Xanthomonas， Lactobacillus， Stutzerimonas， Providencia， Arcobacter， Cutibacterium， Enterococcus， and Thermus were significantly enriched in the ART group， while Pseudomonas， Azospirillum， Escherichia， Acinetobacter， and Stenotrophomonas were significantly enriched in the naive group. Further linear discriminant analysis effect size （LEfSe）（LDA>4， P<0.05） revealed 6 significantly differential species in the ART group and 5 in the naive group. Overall， the richness and diversity of microbiota in the blood of HIV infected individuals significantly improved after treatment. There were significant differences in the dominant species of blood microbiota at the phylum and genus levels between treated and untreated HIV infected individuals， and ART treatment may reduce pathogenic bacteria in the blood. The research results can provide new insights into the interaction between blood microbiota and HIV progression. Specific microbial species can serve as potential indicators for evaluating the effectiveness of HIV treatment and provide a basis for diagnosis and treatment strategy development.

Key words: human immunodeficiency virus, antiretroviral therapy, metagenomics, blood microbiome

中图分类号:

Q814.4

赵靖悦, 温娟, 张荣秋, 张建梅. 抗逆转录病毒治疗对HIV感染者血液微生物组的影响分析[J]. 生物技术进展, 2025, 15(5): 921-929.

Jingyue ZHAO, Juan WEN, Rongqiu ZHANG, Jianmei ZHANG. The Effect of Antiretroviral Therapy on the Blood Microbiome in HIV-infected Individuals[J]. Current Biotechnology, 2025, 15(5): 921-929.

图/表 7

表1 纳入对象基本统计学信息

Table 1 Basic statistical information of the included subjects

	naive组（30例）	ART组（28例）	t/Z值	P值
年龄(岁， $x ¯$ ±s)	35.40±14.83	38.32±12.07	0.819	0.416
性别(例/%)			-	0.936
男	28（93.33%）	25（89.29%）
女	2（6.67%）	3（10.71%）
CD4⁺T淋巴细胞计数（个·μL^-1， $x ¯$ ±s）	252.57±120.20	598.92±211.72	7.728	<0.001
病毒载量[拷贝·mL^-1，M（P₂₅，P₇₅ ）]	115 000（61 750，270 500）	<20*	6.937	<0.001

表1 纳入对象基本统计学信息

Table 1 Basic statistical information of the included subjects

	naive组（30例）	ART组（28例）	t/Z值	P值
年龄(岁， $x ¯$ ±s)	35.40±14.83	38.32±12.07	0.819	0.416
性别(例/%)			-	0.936
男	28（93.33%）	25（89.29%）
女	2（6.67%）	3（10.71%）
CD4⁺T淋巴细胞计数（个·μL^-1， $x ¯$ ±s）	252.57±120.20	598.92±211.72	7.728	<0.001
病毒载量[拷贝·mL^-1，M（P₂₅，P₇₅ ）]	115 000（61 750，270 500）	<20*	6.937	<0.001

图1 物种多样性分析A：2组样品α多样性分析（经Dunn_test和Kruskal test检验）；B：PCoA分析2组样品之间的微生物群落结构差异；****表示差异在P<0.000 1上具有统计学意义

Fig. 1 Analysis of microbial diversity

图2 门水平的物种组成

Fig. 2 Species composition at the phylum levels

表2 门水平丰度的差异分析[中位数（四分位数间距）]

Table 2 Analysis of abundance differences at the phylum level [M（P25,P75）]

门水平	ART组/%	naive组/%	Z值	P值
假单胞菌门Pseudomonadota	90.60(86.23，92.38)	98.14(97.78，98.53)	6.536	<0.001
芽孢杆菌门Bacillota	3.12(2.31，3.66)	0.00(0.00，0.09)	6.409	<0.001
放线菌门Actinomycetota	2.39(1.78，3.23)	1.51(1.16，1.74)	4.770	<0.001
弯曲杆菌门Campylobacterota	1.45(1.07，2.31)	0.00(0.00，0.00)	6.937	<0.001
奇异球菌门Deinococcota	1.03(0.46，1.45)	0.00(0.00，0.00)	6.504	<0.001
拟杆菌门Bacteroidota	0.28(0.19，0.47)	0.09(0.00，0.13)	5.026	<0.001
子囊菌门Ascomycota	0.14(0.00，0.31)	0.00(0.00，0.00)	3.842	<0.001
担子菌门Basidiomycota	0.16(0.09，0.24)	0.00(0.00，0.04)	5.047	<0.001

图3 属水平的物种组成情况

Fig. 3 Species composition at the genus level

图4 组间优势属水平物种的相对丰度差异A：ART组优势属组间差异；B：naive组优势属组间差异。**、***分别表示差异在P<0.01、P<0.001水平上具有统计学意义

Fig. 4 Relative abundance difference of dominant species at the genus level

图5 LEfSe分析

Fig. 5 LEfSe analysis

参考文献 32

[1]	GENG S T, ZHANG Z Y, WANG Y X, et al.. Regulation of gut microbiota on immune reconstitution in patients with acquired immunodeficiency syndrome[J/OL]. Front. Microbiol., 2020, 11: 594820[2025-09-11]. .
[2]	LI J, CHANG S, GUO H, et al.. Altered salivary microbiome in the early stage of HIV infections among young Chinese men who have sex with men (MSM)[J/OL]. Pathogens, 2020, 9(11): E960[2025-09-11]. .
[3]	SPEAR G T, SIKAROODI M, ZARIFFARD M R, et al.. Comparison of the diversity of the vaginal microbiota in HIV-infected and HIV-uninfected women with or without bacterial vaginosis[J]. J. Infect. Dis., 2008, 198(8): 1131-1140.
[4]	张双霞,白会会,张展,等.妊娠期人类免疫缺陷病毒感染对阴道微生物菌群的影响[J].中国医药导报,2024,21(16):119-123.
	ZHANG S X, BAI H H, ZHANG Z, et al.. Effects of human immunodeficiency virus infection during pregnancy on vaginal microbiota[J]. China Med. Her., 2024, 21(16): 119-123.
[5]	RUNTUWENE L R, PARBIE P K, MIZUTANI T, et al.. Longitudinal analysis of microbiome composition in Ghanaians living with HIV-1[J/OL]. Front. Microbiol., 2024, 15: 1359402[2025-09-11]. .
[6]	BEALL C J, LILLY E A, GRANADA C, et al.. Independent effects of HIV and antiretroviral therapy on the oral microbiome identified by multivariate analyses[J/OL]. mBio, 2023, 14(3): e0040923[2025-09-11]. .
[7]	POTGIETER M, BESTER J, KELL D B, et al.. The dormant blood microbiome in chronic, inflammatory diseases[J]. FEMS Microbiol. Rev., 2015, 39(4): 567-591.
[8]	CHENG H S, TAN S P, WONG D M K, et al.. The blood microbiome and health: current evidence, controversies, and challenges[J/OL]. Int. J. Mol. Sci., 2023, 24(6): 5633[2025-09-11]. .
[9]	ZEVIN A S, MCKINNON L, BURGENER A, et al.. Microbial translocation and microbiome dysbiosis in HIV-associated immune activation[J]. Curr. Opin. HIV AIDS, 2016, 11(2): 182-190.
[10]	王玉静,陆梓涔,陈俊煜,等.高通量测序技术的发展及其在临床检测中的应用[J].厦门大学学报(自然科学版),2021,60(5):811-820.
	WANG Y J, LU Z C, CHEN J Y, et al.. Development of the high-throughput sequencing technology and its application in clinical detection[J]. J. Xiamen Univ. Nat. Sci., 2021, 60(5): 811-820.
[11]	LI X, HU H, REN Q, et al.. Comparative analysis of endophyte diversity of Dendrobium officinale lived on rock and tree[J]. Plant Biotechnol., 2023, 40(2): 145-155.
[12]	ZHANG H, HUANG Y, LI X, et al.. Dynamic process of secondary pulmonary infection in mice with intracerebral hemorrhage[J/OL]. Front. Immunol., 2021, 12: 767155[2025-09-11]. .
[13]	黄坤,赵晓琳,程建平,等.胃癌患者胃黏膜微生物群落结构特征分析[J].中国中西医结合消化杂志,2024,32(1):18-22.
	HUANG K, ZHAO X L, CHENG J P, et al.. Analysis of the composition and diversity of gastric microbiome in patients with gastric cancer[J]. Chin. J. Integr. Tradit. West. Med. Dig., 2024, 32(1): 18-22.
[14]	AMAR J, LANGE C, PAYROS G, et al.. Blood microbiota dysbiosis is associated with the onset of cardiovascular events in a large general population: the D.E.S.I.R. study[J/OL]. PLoS ONE, 2013, 8(1): e54461[2025-09-11]. .
[15]	DERESCHUK K, APOSTOL L, RANJAN I, et al.. Identification of lung and blood microbiota implicated in COVID-19 prognosis[J/OL]. Cells, 2021, 10(6): 1452[2025-09-11]. .
[16]	JING Y, ZHOU H, LU H, et al.. Associations between peripheral blood microbiome and the risk of hypertension[J]. Am. J. Hypertens., 2021, 34(10): 1064-1070.
[17]	JAMES W A, OGUNRINDE E, WAN Z, et al.. A distinct plasma microbiome but not gut microbiome in patients with systemic lupus erythematosus compared to healthy individuals[J]. J. Rheumatol., 2022, 49(6): 592-597.
[18]	NGANOU-MAKAMDOP K, TALLA A, SHARMA A A, et al.. Translocated microbiome composition determines immunological outcome in treated HIV infection[J]. Cell, 2021, 184(15): 3899-3914.
[19]	SERRANO-VILLAR S, SANCHEZ-CARRILLO S, TALAVERA-RODRÍGUEZ A, et al.. Blood bacterial profiles associated with human immunodeficiency virus infection and immune recovery[J]. J. Infect. Dis., 2021, 223(3): 471-481.
[20]	AKO S E, NKENFOU C N, ASSOB J N, et al.. Characterization and profiling of gut bacterial microbiome and pathobionts among HIV-negative and HIV-infected individuals in Cameroon[J]. Int. J. Trop. Dis. Health, 2023, 44(9): 46-65.
[21]	RUSSOTTO Y, MICALI C, PELLICANÒ G F, et al.. HIV and Mediterranean zoonoses: a review of the literature[J]. Infect. Dis. Rep., 2022, 14(5): 694-709.
[22]	MUNJOMA P T, CHANDIWANA P, WYSS J, et al.. Immune activation and inflammation in lactating women on combination antiretroviral therapy: role of gut dysfunction and gut microbiota imbalance[J/OL]. Front. Immunol., 2023, 14: 1280262[2025-09-11]. .
[23]	ERICSEN A J, LAUCK M, MOHNS M S, et al.. Microbial translocation and inflammation occur in hyperacute immunodeficiency virus infection and compromise host control of virus replication[J/OL]. PLoS Pathog., 2016, 12(12): e1006048[2025-09-11]. .
[24]	PAÏSSÉ S, VALLE C, SERVANT F, et al.. Comprehensive description of blood microbiome from healthy donors assessed by 16S targeted metagenomic sequencing[J]. Transfusion, 2016, 56(5): 1138-1147.
[25]	ZHAO M, LI Y, GAO Z, et al.. Plasma metagenomics reveals regional variations of emerging and re-emerging pathogens in Chinese blood donors with an emphasis on human parvovirus B19[J/OL]. One Health, 2023, 17: 100602[2025-09-11]. .
[26]	朱林,王琪琪,徐玉莲,等.健康人血液微生物宏基因组和噬菌体组的深度挖掘分析[J].中国输血杂志,2024,37(10):1091-1100.
	ZHU L, WANG Q Q, XU Y L, et al.. Deep mining of healthy blood metagenomics and phageomes[J]. Chin. J. Blood Transfus., 2024, 37(10): 1091-1100.
[27]	李昱辉,刘志阳,高瞻,等.HIV病毒感染不同阶段的合并感染病原体种类分析[J].中国输血杂志,2020,33(9):894-898.
	LI Y H, LIU Z Y, GAO Z, et al.. Analysis of co-infected pathogens in HIV infected individuals at different stages[J]. Chin. J. Blood Transfus., 2020, 33(9): 894-898.
[28]	WU Y, GONG Y, ZHANG Y, et al.. Comparative analysis of gut microbiota from rats induced by Se deficiency and T-2 toxin[J/OL]. Nutrients, 2023, 15(24): 5027[2025-09-11]. .
[29]	CHABALA F, MADUBASI M, MUTENGO M M, et al.. Escherichia coli antimicrobial susceptibility reduction amongst HIV-infected individuals at the university teaching hospital, Lusaka, Zambia[J/OL]. Int. J. Environ. Res. Public Health, 2020, 17(10): 3355[2025-09-11]. .
[30]	OKOROR L E, FASHINA D C, JIMOH T S, et al.. Molecular epidemiology of Escherichia coli in HIV-positive individuals in south west Nigeria [J/OL]. Int. Arch. Med., 2015: 53978951 [2025-09-11]. .
[31]	SINGH R P, SINHA A, DEB S, et al.. First report on in-depth genome and comparative genome analysis of a metal-resistant bacterium Acinetobacter pittii S-30, isolated from environmental sample[J/OL]. Front. Microbiol., 2024, 15: 1351161[2025-09-11]. .
[32]	MO L, SU G, LAN J, et al.. Investigation and analysis on pathogen distribution of HIV/AIDS patients with opportunistic infection[J]. Adv. Infect. Dis., 2015, 5(4): 167-173.

抗逆转录病毒治疗对HIV感染者血液微生物组的影响分析

The Effect of Antiretroviral Therapy on the Blood Microbiome in HIV-infected Individuals

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 7

参考文献 32

相关文章 5

编辑推荐

Metrics

本文评价

[1]	曹海涛, 朱静, 曾海波, 刘彦辰. 基于加权平均的肠道菌群特征筛选和疾病预测模型研究[J]. 生物技术进展, 2023, 13(5): 798-806.
[2]	李伟, 王冲, 刘嗣嘉, 杨敏一, 张云平. 宏基因组学技术在痤疮研究中的应用进展[J]. 生物技术进展, 2021, 11(6): 694-699.
[3]	董俊帅,秦星,张志伟,张宇宏,张伟. 宏基因组来源果胶酸裂解酶在毕赤酵母中的表达及应用[J]. 生物技术进展, 2018, 8(3): 237-245.
[4]	王海东,胡忠. 利用宏基因组法筛选新几丁质酶基因[J]. 生物技术进展, 2016, 6(2): 119-124.
[5]	吴森,张莺莺,昝林森, . 基于高通量测序的宏基因组学技术在动物胃肠道微生物方面的研究进展[J]. 生物技术进展, 2015, 5(2): 77-84.