巴西里约热内卢一项关于 HIV 单一感染人群肝脏疾病微生物特征的初步研究。
A pilot study of microbial signatures of liver disease in those with HIV mono-infection in Rio de Janeiro, Brazil.
机构信息
Laboratory of Clinical Research in STD/AIDS (LAPCLIN-AIDS), Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation (INI/FIOCRUZ), Rio de Janeiro, Brazil.
Department of Pediatrics, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
出版信息
AIDS. 2022 Jan 1;36(1):49-58. doi: 10.1097/QAD.0000000000003084.
OBJECTIVE
The rectal microbiome was examined to assess the relationship between the microbiome and liver disease in HIV-infection.
DESIGN
Eighty-two HIV-1 mono-infected individuals from the PROSPEC-HIV-study (NCT02542020) were grouped into three liver health categories based on results of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) of transient elastography: normal (n = 30), steatosis (n = 30), or fibrosis (n = 22).
METHODS
Liver steatosis and fibrosis were defined by CAP at least 248 dB/m and LSM at least 8.0 kPa, respectively. 16S rRNA gene and whole genome shotgun metagenomic sequencing were performed on rectal swabs. Bacterial differences were assessed using zero-inflated negative binomial regression and random forests modeling; taxonomic drivers of functional shifts were identified using FishTaco.
RESULTS
Liver health status explained four percentage of the overall variation (r2 = 0.04, P = 0.003) in bacterial composition. Participants with steatosis had depletions of Akkermansia muciniphila and Bacteroides dorei and enrichment of Prevotella copri, Finegoldia magna, and Ruminococcus bromii. Participants with fibrosis had depletions of Bacteroides stercoris and Parabacteroides distasonis and enrichment of Sneathia sanguinegens. In steatosis, functional analysis revealed increases in primary and secondary bile acid synthesis encoded by increased Eubacterium rectale, F. magna, and Faecalibacterium prausnitzii and decreased A. muciniphila, Bacteroides fragilis and B. dorei. Decreased folate biosynthesis was driven by similar changes in microbial composition.
CONCLUSION
HIV mono-infection with steatosis or fibrosis had distinct microbial profiles. Some taxa are similar to those associated with non-alcoholic fatty liver disease in HIV-negative populations. Further studies are needed to define the role of the gut microbiota in the pathogenesis of liver disease in HIV-infected persons.
目的
通过检查直肠微生物组来评估 HIV 感染中微生物组与肝病之间的关系。
设计
根据控制衰减参数 (CAP) 和瞬时弹性成像肝硬度测量 (LSM) 的结果，将 PROSPEC-HIV 研究 (NCT02542020) 中的 82 名 HIV-1 单感染个体分为三组肝脏健康类别：正常 (n = 30)、脂肪变性 (n = 30) 或纤维化 (n = 22)。
方法
肝脂肪变性和纤维化分别定义为 CAP 至少 248 dB/m 和 LSM 至少 8.0 kPa。对直肠拭子进行 16S rRNA 基因和全基因组鸟枪法宏基因组测序。使用零膨胀负二项式回归和随机森林模型评估细菌差异；使用 FishTaco 鉴定功能变化的分类驱动因素。
结果
肝脏健康状况解释了细菌组成总体变化的四个百分点 (r2 = 0.04，P = 0.003)。脂肪变性患者 Akkermansia muciniphila 和 Bacteroides dorei 减少，Prevotella copri、Finegoldia magna 和 Ruminococcus bromii 富集。纤维化患者 Bacteroides stercoris 和 Parabacteroides distasonis 减少，Sneathia sanguinegens 富集。在脂肪变性中，功能分析显示，Eubacterium rectale、F. magna 和 Faecalibacterium prausnitzii 编码的初级和次级胆汁酸合成增加，A. muciniphila、Bacteroides fragilis 和 B. dorei 减少。由于微生物组成的相似变化，叶酸生物合成减少。
结论
HIV 单感染伴脂肪变性或纤维化具有独特的微生物特征。一些分类群与 HIV 阴性人群中非酒精性脂肪性肝病相关的分类群相似。需要进一步研究来确定肠道微生物群在 HIV 感染者肝病发病机制中的作用。
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