抗逆转录病毒治疗的围生期 HIV 感染患者的肠道微生物群特征与心脏和炎症生物标志物相关。

Distinct gut microbiota profile in antiretroviral therapy-treated perinatally HIV-infected patients associated with cardiac and inflammatory biomarkers.

机构信息

Department of Public Health, University of Rome 'Tor Vergata'.

Human Microbiome Unit, Bambino Gesù Children's Hospital, IRCCS, Rome.

出版信息

AIDS. 2019 May 1;33(6):1001-1011. doi: 10.1097/QAD.0000000000002131.

DOI:10.1097/QAD.0000000000002131

PMID:30946154

Abstract

OBJECTIVE

Persistent inflammation and higher risk to develop cardiovascular diseases still represent a major complication for HIV-infected patients despite effective antiretroviral therapy (ART). We investigated the correlation between the gut microbiota profile, markers of inflammation, vascular endothelial activation (VEA) and microbial translocation (MT) in perinatally HIV-infected patients (PHIV) under ART.

DESIGN

Cross-sectional study including 61 ART-treated PHIV (age range 3-30 years old) and 71 age-matched healthy controls. Blood and stool sample were collected at the same time and analyzed for gut microbiota composition and plasma biomarkers.

METHODS

Gut microbiota composition was determined by 16S rRNA targeted-metagenomics. Soluble markers of MT, inflammation and VEA were quantified by ELISA or Luminex assay. Markers of immune activation were analyzed by flow cytometry on CD4 and CD8T cells.

RESULTS

We identified two distinct gut microbiota profiles (groups A and B) among PHIV. No different clinical parameters (age, sex, ethnicity, clinical class), dietary and sexual habits were found between the groups. The group A showed a relative dominance of Akkermansia muciniphila, whereas gut microbiota of group B was characterized by a higher biodiversity. The analysis of soluble markers revealed a significantly higher level of soluble E-selectine (P = 0.0296), intercellular adhesion molecule-1 (P = 0.0028), vascular adhesion molecule-1 (P = 0.0230), IL-6 (P = 0.0247) and soluble CD14 (P = 0.0142) in group A compared with group B.

CONCLUSION

Distinctive gut microbiota profiles are differently associated with inflammation, microbial translocation and VEA. Future studies are needed to understand the role of A. muciniphila and risk to develop cardiovascular diseases in PHIV.

摘要

目的

尽管抗逆转录病毒疗法（ART）有效，但持续性炎症和更高的心血管疾病风险仍然是 HIV 感染患者的主要并发症。我们研究了接受 ART 的围生期 HIV 感染患者（PHIV）的肠道微生物群谱、炎症标志物、血管内皮激活（VEA）和微生物易位（MT）之间的相关性。

设计

包括 61 名接受 ART 治疗的 PHIV（年龄 3-30 岁）和 71 名年龄匹配的健康对照的横断面研究。同时采集血液和粪便样本，并进行肠道微生物群组成和血浆生物标志物分析。

方法

通过 16S rRNA 靶向宏基因组学确定肠道微生物群组成。通过 ELISA 或 Luminex 测定法定量测定 MT、炎症和 VEA 的可溶性标志物。通过 CD4 和 CD8T 细胞的流式细胞术分析免疫激活标志物。

结果

我们在 PHIV 中鉴定出两种不同的肠道微生物群谱（A 组和 B 组）。两组之间无不同的临床参数（年龄、性别、种族、临床分类）、饮食和性行为。A 组显示阿克曼氏菌（Akkermansia muciniphila）相对占优势，而 B 组的肠道微生物群则具有更高的多样性。可溶性标志物分析显示，A 组可溶性 E-选择素（P=0.0296）、细胞间黏附分子-1（P=0.0028）、血管细胞黏附分子-1（P=0.0230）、白细胞介素-6（P=0.0247）和可溶性 CD14（P=0.0142）水平明显高于 B 组。