학술논문

Widespread Colonization of the Lung by Tropheryma whipplei in HIV Infection
Document Type
article
Source
American Journal of Respiratory and Critical Care Medicine. 187(10)
Subject
Medical Microbiology
Biomedical and Clinical Sciences
Genetics
Lung
Human Genome
Infectious Diseases
HIV/AIDS
Clinical Research
2.1 Biological and endogenous factors
2.2 Factors relating to the physical environment
Aetiology
Respiratory
Infection
Cohort Studies
HIV Infections
Humans
Longitudinal Studies
Tropheryma
Whipple Disease
human
microbiome
metagenome
16S ribosomal RNA
bronchoalveolar lavage
Lung HIV Microbiome Project
Medical and Health Sciences
Respiratory System
Cardiovascular medicine and haematology
Clinical sciences
Language
Abstract
RationaleLung infections caused by opportunistic or virulent pathogens are a principal cause of morbidity and mortality in HIV infection. It is unknown whether HIV infection leads to changes in basal lung microflora, which may contribute to chronic pulmonary complications that increasingly are being recognized in individuals infected with HIV.ObjectivesTo determine whether the immunodeficiency associated with HIV infection resulted in alteration of the lung microbiota.MethodsWe used 16S ribosomal RNA targeted pyrosequencing and shotgun metagenomic sequencing to analyze bacterial gene sequences in bronchoalveolar lavage (BAL) and mouths of 82 HIV-positive and 77 HIV-negative subjects.Measurements and main resultsSequences representing Tropheryma whipplei, the etiologic agent of Whipple's disease, were significantly more frequent in BAL of HIV-positive compared with HIV-negative individuals. T. whipplei dominated the community (>50% of sequence reads) in 11 HIV-positive subjects, but only 1 HIV-negative individual (13.4 versus 1.3%; P = 0.0018). In 30 HIV-positive individuals sampled longitudinally, antiretroviral therapy resulted in a significantly reduced relative abundance of T. whipplei in the lung. Shotgun metagenomic sequencing was performed on eight BAL samples dominated by T. whipplei 16S ribosomal RNA. Whole genome assembly of pooled reads showed that uncultured lung-derived T. whipplei had similar gene content to two isolates obtained from subjects with Whipple's disease.ConclusionsAsymptomatic subjects with HIV infection have unexpected colonization of the lung by T. whipplei, which is reduced by effective antiretroviral therapy and merits further study for a potential pathogenic role in chronic pulmonary complications of HIV infection.