Dataset Information

Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease.

ABSTRACT: Microbiome studies typically focus on bacteria, but fungal species are common in many body sites and can have profound effects on the host. Wide gaps exist in the understanding of the fungal microbiome (mycobiome) and its relationship to lung disease.To characterize the mycobiome at different respiratory tract levels in persons with and without HIV infection and in HIV-infected individuals with chronic obstructive pulmonary disease (COPD).Oral washes (OW), induced sputa (IS), and bronchoalveolar lavages (BAL) were collected from 56 participants. We performed 18S and internal transcribed spacer sequencing and used the neutral model to identify fungal species that are likely residents of the lung. We used ubiquity-ubiquity plots, random forest, logistic regression, and metastats to compare fungal communities by HIV status and presence of COPD.Mycobiomes of OW, IS, and BAL shared common organisms, but each also had distinct members. Candida was dominant in OW and IS, but BAL had 39 fungal species that were disproportionately more abundant than in the OW. Fungal communities in BAL differed significantly by HIV status and by COPD, with Pneumocystis jirovecii significantly overrepresented in both groups. Other fungal species were also identified as differing in HIV and COPD.This study systematically examined the respiratory tract mycobiome in a relatively large group. By identifying Pneumocystis and other fungal species as overrepresented in the lung in HIV and in COPD, it is the first to determine alterations in fungal communities associated with lung dysfunction and/or HIV, highlighting the clinical relevance of these findings. Clinical trial registered with www.clinicaltrials.gov (NCT00870857).

SUBMITTER: Cui L

PROVIDER: S-EPMC4435454 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease.

Cui Lijia L Lucht Lorrie L Tipton Laura L Rogers Matthew B MB Fitch Adam A Kessinger Cathy C Camp Danielle D Kingsley Lawrence L Leo Nicolas N Greenblatt Ruth M RM Fong Serena S Stone Stephen S Dermand John C JC Kleerup Eric C EC Huang Laurence L Morris Alison A Ghedin Elodie E

American journal of respiratory and critical care medicine 20150401 8

<h4>Rationale</h4>Microbiome studies typically focus on bacteria, but fungal species are common in many body sites and can have profound effects on the host. Wide gaps exist in the understanding of the fungal microbiome (mycobiome) and its relationship to lung disease.<h4>Objectives</h4>To characterize the mycobiome at different respiratory tract levels in persons with and without HIV infection and in HIV-infected individuals with chronic obstructive pulmonary disease (COPD).<h4>Methods</h4>Oral ...[more]

PMID: 25603113

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Project description:Invasive fungal infections are an increasingly important cause of human morbidity and mortality. We generated a next-generation sequencing (NGS)-based method designed to detect a wide range of fungi and applied it to analysis of the fungal microbiome (mycobiome) of the lung during fungal infection. Internal transcribed spacer 1 (ITS1) amplicon sequencing and a custom analysis pipeline detected 96% of species from three mock communities comprised of potential fungal lung pathogens with good recapitulation of the expected species distributions (Pearson correlation coefficients r = 0.63, p = 0.004; r = 0.71, p < 0.001; r = 0.62, p = 0.002). We used this pipeline to analyze mycobiomes of bronchoalveolar lavage (BAL) specimens classified as culture-negative (n = 50) or culture-positive (n = 39) for Blastomyces dermatitidis/gilchristii, the causative agent of North America blastomycosis. Detected in 91.4% of the culture-positive samples, Blastomyces dominated (>50% relative abundance) the mycobiome in 68.6% of these culture-positive samples but was absent in culture-negative samples. To overcome any bias in relative abundance due to between-sample variation in fungal biomass, an abundance-weighting calculation was used to normalize the data by accounting for sample-specific PCR cycle number and PCR product concentration data utilized during sample preparation. After normalization, there was a statistically significant greater overall abundance of ITS1 amplicon in the Blastomyces-culture-positive samples versus culture-negative samples. Moreover, the normalization revealed a greater biomass of yeast and environmental fungi in several Blastomyces-culture-positive samples than in the culture-negative samples. Successful detection of Coccidioides, Scedosporium, Phaeoacremonium, and Aspergillus in 6 additional culture-positive BALs by ITS1 amplicon sequencing demonstrates the ability of this method to detect a broad range of fungi from clinical specimens, suggesting that it may be a potentially useful adjunct to traditional fungal microbiological testing for the diagnosis of respiratory mycoses.

Project description:Background and objectiveThe lung microbiome was previously thought to be a sterile environment where only gaseous exchange takes place, but recent studies have shown the presence of microbiota in the lung. This review investigates the current literature on the effects of an environmental driven dysbiosis on the healthy oral and respiratory microbiome and its relationship to lung cancer risk in never-smokers.MethodsAn online electronic search was performed on PubMed of all English-language literature using combinations of the following keywords: "lung cancer", "dysbiosis", "non-smokers", "oral microbiome", and "respiratory microbiome". All population-based studies reporting results on oral and/or respiratory microbiome in adults were considered for our narrative review.Key content and findingsMetagenomic analyses have been performed on isolated samples from healthy participants and compared to samples from those with lung cancer. Research shows that a decrease in alpha diversity of microbes in the oral microbiome is associated with increased risk of lung cancer, along with differences in beta diversity in the sputum of lung cancer cases and healthy controls. Further, several studies have observed that significant changes in the abundance of genera such as increased abundance of Lactobacillales, Bacilli, and Firmicutes associated with an increased lung cancer risk among participants with exposure to certain household solid fuels.ConclusionsThese findings suggest potential carcinogenic processes such as increased inflammation associated with changes in flora. Additionally, studies showed that increase in certain taxa such as Bacteroides and Spirochetes might have a protective effect on lung cancer risk. The review also provides insight into how understanding the microbial changes can be beneficial for lung cancer treatment and disease-free survival. Larger studies in different populations need to be performed to strengthen the current associations between microbial diversity and lung cancer risk.

Dataset Information

Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease.

Publications

Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease.

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