Effects of Early Antiretroviral Therapy on the Composition and Diversity of the Fecal Microbiome of SIV-infected Rhesus Macaques (Macaca mulatta).

IF 1.3 4区 农林科学 Q2 VETERINARY SCIENCES Comparative medicine Pub Date : 2022-10-01 DOI:10.30802/AALAS-CM-22-000020
Tiffany R Lavinder, Devin N Fachko, Jeffrey Stanton, Benjamin Varco-Merth, Jeremy Smedley, Afam A Okoye, Rebecca L Skalsky
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Abstract

HIV-infected people develop reproducible disruptions in their gastrointestinal microbiota. Despite the suppression of HIV viremia via long-term antiretroviral therapy (ART), alterations still occur in gut microbial diversity and the commensal microbiota. Mounting evidence suggests these microbial changes lead to the development of gut dysbiosis-persistent inflammation that damages the gut mucosa-and correlate with various immune defects. In this study, we examined how early ART intervention influences microbial diversity in SIV-infected rhesus macaques. Using 16S rRNA sequencing, we defined the fecal microbiome in macaques given daily ART beginning on either 3 or 7 d after SIV infection (dpi) and characterized changes in composition, α diversity, and β diversity from before infection through 112 dpi. The dominant phyla in the fecal samples before infection were Bacteroidetes, Firmicutes, Spirochaetes, and Proteobacteria. After SIV infection and ART, the relative abundance of Firmicutes and Bacteroidetes did not change significantly. Significant reductions in α diversity occurred across time when ART was initiated at 3 dpi but not at 7 dpi. Principal coordinate analysis of samples revealed a divergence in β diversity in both treatment groups after SIV infection, with significant differences depending on the timing of ART administration. These results indicate that although administration of ART at 3 or 7 dpi did not substantially alter fecal microbial composition, the timing of early ART measurably altered phylogenetic diversity.

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早期抗逆转录病毒治疗对siv感染恒河猴粪便微生物组成和多样性的影响
艾滋病毒感染者的胃肠道微生物群出现可重复的破坏。尽管通过长期抗逆转录病毒治疗(ART)抑制了HIV病毒血症,但肠道微生物多样性和共生微生物群仍会发生变化。越来越多的证据表明,这些微生物的变化会导致肠道生态失调的发展——持续的炎症会损害肠道黏膜——并与各种免疫缺陷相关。在这项研究中,我们研究了早期ART干预如何影响siv感染恒河猴的微生物多样性。利用16S rRNA测序技术,研究人员确定了SIV感染后3天或7天每天给予抗逆转录病毒治疗的猕猴粪便微生物组,并表征了其组成、α多样性和β多样性从感染前到感染后112 dpi的变化。感染前粪便样品的优势门为拟杆菌门、厚壁菌门、螺旋体门和变形菌门。经SIV感染和抗逆转录病毒治疗后,厚壁菌门和拟杆菌门的相对丰度没有明显变化。在3 dpi开始ART时,α多样性显著减少,而在7 dpi时则没有。样本的主坐标分析显示,在SIV感染后,两个治疗组的β多样性存在差异,这取决于抗逆转录病毒治疗的时间。这些结果表明,尽管在3或7 dpi时给予ART并没有实质性地改变粪便微生物组成,但早期ART的时间可测量地改变了系统发育多样性。
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来源期刊
Comparative medicine
Comparative medicine 医学-动物学
CiteScore
1.90
自引率
0.00%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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