PDF(Pubmed)
Abstract：
BACKGROUND: People living with HIV (PLWH) are at increased risk of acquisition of multidrug resistant organisms due to higher rates of predisposing factors. The gut microbiome is the main reservoir of the collection of antimicrobial resistance determinants known as the gut resistome. In PLWH, changes in gut microbiome have been linked to immune activation and HIV-1 associated complications. Specifically, gut dysbiosis defined by low microbial gene richness has been linked to low Nadir CD4 + T-cell counts. Additionally, sexual preference has been shown to strongly influence gut microbiome composition in PLWH resulting in different Prevotella or Bacteroides enriched enterotypes, in MSM (men-who-have-sex-with-men) or no-MSM, respectively. To date, little is known about gut resistome composition in PLWH due to the scarcity of studies using shotgun metagenomics. The present study aimed to detect associations between different microbiome features linked to HIV-1 infection and gut resistome composition.
RESULTS: Using shotgun metagenomics we characterized the gut resistome composition of 129 HIV-1 infected subjects showing different HIV clinical profiles and 27 HIV-1 negative controls from a cross-sectional observational study conducted in Barcelona, Spain. Most no-MSM showed a Bacteroides-enriched enterotype and low microbial gene richness microbiomes. We did not identify differences in resistome diversity and composition according to HIV-1 infection or immune status. However, gut resistome was more diverse in MSM group, Prevotella-enriched enterotype and gut micorbiomes with high microbial gene richness compared to no-MSM group, Bacteroides-enriched enterotype and gut microbiomes with low microbial gene richness. Additionally, gut resistome beta-diversity was different according to the defined groups and we identified a set of differentially abundant antimicrobial resistance determinants based on the established categories.
CONCLUSIONS: Our findings reveal a significant correlation between gut resistome composition and various host variables commonly associated with gut microbiome, including microbiome enterotype, microbial gene richness, and sexual preference. These host variables have been previously linked to immune activation and lower Nadir CD4 + T-Cell counts, which are prognostic factors of HIV-related comorbidities. This study provides new insights into the relationship between antibiotic resistance and clinical characteristics of PLWH.
RESULTS: Using shotgun metagenomics we characterized the gut resistome composition of 129 HIV-1 infected subjects showing different HIV clinical profiles and 27 HIV-1 negative controls from a cross-sectional observational study conducted in Barcelona, Spain. Most no-MSM showed a Bacteroides-enriched enterotype and low microbial gene richness microbiomes. We did not identify differences in resistome diversity and composition according to HIV-1 infection or immune status. However, gut resistome was more diverse in MSM group, Prevotella-enriched enterotype and gut micorbiomes with high microbial gene richness compared to no-MSM group, Bacteroides-enriched enterotype and gut microbiomes with low microbial gene richness. Additionally, gut resistome beta-diversity was different according to the defined groups and we identified a set of differentially abundant antimicrobial resistance determinants based on the established categories.
CONCLUSIONS: Our findings reveal a significant correlation between gut resistome composition and various host variables commonly associated with gut microbiome, including microbiome enterotype, microbial gene richness, and sexual preference. These host variables have been previously linked to immune activation and lower Nadir CD4 + T-Cell counts, which are prognostic factors of HIV-related comorbidities. This study provides new insights into the relationship between antibiotic resistance and clinical characteristics of PLWH.
摘要：
背景：由于易感因素的发生率较高，HIV感染者（PLWH）获得多药耐药生物的风险增加。肠道微生物组是被称为肠道抗性组的抗微生物抗性决定子集合的主要储库。在PLWH中,肠道微生物组的变化与免疫激活和HIV-1相关并发症有关.具体来说,由低微生物基因丰富度定义的肠道生态失调与较低的最低点CD4T细胞计数有关。此外,性偏好已被证明强烈影响PLWH的肠道微生物组组成，导致不同的普雷沃氏菌或富含拟杆菌的肠型，在MSM（与男性发生性关系的男性）或非MSM中，分别。迄今为止,由于缺乏使用shot弹枪宏基因组学的研究，因此对PLWH中的肠道耐药性组成知之甚少。本研究旨在检测与HIV-1感染相关的不同微生物组特征与肠道耐药性组成之间的关联。
结果：使用鸟枪宏基因组学，我们在巴塞罗那进行的一项横断面观察研究中，对129名HIV-1感染受试者的肠道耐药性组成进行了表征，这些受试者显示出不同的HIV临床特征和27名HIV-1阴性对照。西班牙。大多数无MSM显示出富含拟杆菌的肠型和低微生物基因丰富度的微生物组。根据HIV-1感染或免疫状态，我们没有确定抗性组多样性和组成的差异。然而,MSM组的肠道耐药组更加多样化，与无MSM组相比，富含Prevotella的肠型和肠道微生物群具有较高的微生物基因丰富度，富含拟杆菌的肠型和具有低微生物基因丰富度的肠道微生物。此外,根据定义的组，肠道耐药组β-多样性是不同的，我们根据已建立的类别确定了一组差异丰富的抗微生物耐药性决定因素。
结论：我们的发现揭示了肠道耐药性组成与通常与肠道微生物组相关的各种宿主变量之间的显著相关性，包括肠道菌群，微生物基因丰富度，和性偏好。这些宿主变量以前与免疫激活和较低的NadirCD4T细胞计数有关，这是HIV相关合并症的预后因素。本研究为PLWH的临床特征与抗生素耐药性之间的关系提供了新的见解。
结果：使用鸟枪宏基因组学，我们在巴塞罗那进行的一项横断面观察研究中，对129名HIV-1感染受试者的肠道耐药性组成进行了表征，这些受试者显示出不同的HIV临床特征和27名HIV-1阴性对照。西班牙。大多数无MSM显示出富含拟杆菌的肠型和低微生物基因丰富度的微生物组。根据HIV-1感染或免疫状态，我们没有确定抗性组多样性和组成的差异。然而,MSM组的肠道耐药组更加多样化，与无MSM组相比，富含Prevotella的肠型和肠道微生物群具有较高的微生物基因丰富度，富含拟杆菌的肠型和具有低微生物基因丰富度的肠道微生物。此外,根据定义的组，肠道耐药组β-多样性是不同的，我们根据已建立的类别确定了一组差异丰富的抗微生物耐药性决定因素。
结论：我们的发现揭示了肠道耐药性组成与通常与肠道微生物组相关的各种宿主变量之间的显著相关性，包括肠道菌群，微生物基因丰富度，和性偏好。这些宿主变量以前与免疫激活和较低的NadirCD4T细胞计数有关，这是HIV相关合并症的预后因素。本研究为PLWH的临床特征与抗生素耐药性之间的关系提供了新的见解。
