Supraglottic Lung Microbiome Taxa Are Associated with Pulmonary Abnormalities in an HIV Longitudinal Cohort.
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ABSTRACT:
SUBMITTER: Zhou JJ
PROVIDER: S-EPMC7737582 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The lung microbiome of healthy individuals frequently harbors oral organisms. Despite evidence that microaspiration is commonly associated with smoking-related lung diseases, the effects of lung microbiome enrichment with upper airway taxa on inflammation has not been studied. We hypothesize that the presence of oral microorganisms in the lung microbiome is associated with enhanced pulmonary inflammation. To test this, we sampled bronchoalveolar lavage (BAL) from the lower airways of 29 asymptomatic subjects (nine never-smokers, 14 former-smokers, and six current-smokers). We quantified, amplified, and sequenced 16S rRNA genes from BAL samples by qPCR and 454 sequencing. Pulmonary inflammation was assessed by exhaled nitric oxide (eNO), BAL lymphocytes, and neutrophils.BAL had lower total 16S than supraglottic samples and higher than saline background. Bacterial communities in the lower airway clustered in two distinct groups that we designated as pneumotypes. The rRNA gene concentration and microbial community of the first pneumotype was similar to that of the saline background. The second pneumotype had higher rRNA gene concentration and higher relative abundance of supraglottic-characteristic taxa (SCT), such as Veillonella and Prevotella, and we called it pneumotypeSCT. Smoking had no effect on pneumotype allocation, ?, or ? diversity. PneumotypeSCT was associated with higher BAL lymphocyte-count (P= 0.007), BAL neutrophil-count (P= 0.034), and eNO (P= 0.022).A pneumotype with high relative abundance of supraglottic-characteristic taxa is associated with enhanced subclinical lung inflammation.
| S-EPMC3971609 | biostudies-literature
Project description:Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation
| PRJNA210947 | ENA
Project description:Microaspiration is a common phenomenon in healthy subjects, but its frequency is increased in chronic inflammatory airway diseases, and its role in inflammatory and immune phenotypes is unclear. We have previously demonstrated that acellular bronchoalveolar lavage samples from half of the healthy people examined are enriched with oral taxa (here called pneumotypeSPT) and this finding is associated with increased numbers of lymphocytes and neutrophils in bronchoalveolar lavage. Here, we have characterized the inflammatory phenotype using a multi-omic approach. By evaluating both upper airway and acellular bronchoalveolar lavage samples from 49 subjects from three cohorts without known pulmonary disease, we observed that pneumotypeSPT was associated with a distinct metabolic profile, enhanced expression of inflammatory cytokines, a pro-inflammatory phenotype characterized by elevated Th-17 lymphocytes and, conversely, a blunted alveolar macrophage TLR4 response. The cellular immune responses observed in the lower airways of humans with pneumotypeSPT indicate a role for the aspiration-derived microbiota in regulating the basal inflammatory status at the pulmonary mucosal surface.
| S-EPMC5010013 | biostudies-literature
Project description:BACKGROUND:HIV is an independent risk factor for chronic obstructive pulmonary disease; however, baseline risk factors for lung function decline remain largely unknown in this population. METHODS:HIV-infected participants in the Pittsburgh Lung HIV Cohort with at least 3 pulmonary function measurements between 2007 and 2016 were included. Pulmonary function testing including postbronchodilator (BD) spirometry and diffusion capacity for carbon monoxide (DLco) was performed every 18 months. We used a mixed-effect linear model to evaluate factors associated with pulmonary function testing and DLco decline and logistic regression models to evaluate factors associated with rapid FEV1 decline (defined as >80 mL per year) and any DLco decline. RESULTS:Two hundred eighty-five HIV-infected participants were included. Median baseline CD4 cell count was 521 cells per micro liter, 61.9% had an undetectable HIV viral load at baseline, and 78.5% were receiving ART. Approximately 20% of participants met Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for a diagnosis of chronic obstructive pulmonary disease at baseline. Older age and baseline GOLD stage 1 compared with stage 0 were associated with faster decline in post-BD FEV1%, whereas female sex was associated with slower decline. Similarly, female sex was associated with slower decline in DLco%. HIV-related factors including CD4 cell count, viral load, and ART use were not significantly associated with pulmonary function decline. CONCLUSIONS:Older age, male sex, and higher baseline GOLD stage were associated with more rapid post-BD FEV1% decline in HIV-infected individuals.
| S-EPMC6203646 | biostudies-literature
Project description:BACKGROUND:Some patients with chronic obstructive pulmonary disease (COPD) have asthma-like features. However, there have been few reports on the structural lung abnormalities found in this patient population. Multi-detector computed tomography (MDCT) can detect emphysematous low-attenuation areas (LAA) within the lung, airway thickness (wall area percentage, WA%), and the loss of pulmonary vasculature as the percentage of small pulmonary vessels with cross-sectional area (CSA) less than 5 mm2 (%CSA<5). We analyzed differences in structural lung changes over time between patients with COPD and those with COPD with asthma-like features using these CT parameters. MATERIAL AND METHODS:We performed pulmonary function tests (PFTs), MDCT, and a COPD assessment test (CAT) in 50 patients with COPD and 29 patients with COPD with asthma-like features at the time of enrollment and two years later. We analyzed changes in clinical parameters and CT indices over time and evaluated differences in structural changes between groups. RESULTS:The CAT score and FEV1 did not significantly change during the follow-up period in either group. Emphysematous LAA regions significantly increased in both groups. The %CSA<5 showed a small but significant increase in COPD patients, but a significant decrease in patients with COPD with asthma-like features. The WA% at the distal bronchi was significantly decreased in COPD, but did not significantly change in COPD with asthma -like features. CONCLUSION:Emphysematous LAA increased in patients with COPD with and without asthma-like features. The %CSA<5 and WA% at the distal bronchi did not change in parallel with LAA. Furthermore, changes in %CSA<5 were significantly different between patients with COPD and those with COPD with asthma-like features. Patients with COPD with asthma-like features may have different longitudinal structural changes than those seen in COPD patients.
| S-EPMC6936827 | biostudies-literature
Project description:INTRODUCTION:Liver disease is a common cause of non-AIDS morbidity and mortality in people living with HIV (PLHIV), but the prevalence and significance of liver function test (LFT) abnormalities in early HIV infection is unknown. This study aimed to characterize LFTs in a large cohort of participants with acute HIV infection initiating immediate antiretroviral therapy (ART) and examine the association between LFTs and biomarkers of HIV infection and inflammation. METHODS:We measured LFTs at the time of HIV diagnosis and at 4, 12, 24 and 48 weeks after ART initiation in 426 Thai individuals with acute HIV infection from 2009 to 2018. A subset of individuals had data available at 96 and 144 weeks. We excluded individuals with concomitant viral hepatitis. Alanine aminotransferase (ALT) was the primary outcome of interest; values greater than 1.25 times the upper limit of normal were considered elevated. Analyses utilized descriptive statistics, non-parametric tests and multivariate logistic regression. RESULTS:Sixty-six of the 426 individuals (15.5%) had abnormal baseline ALT levels; the majority (43/66, 65.5%) had Grade 1 elevations. Elevated baseline ALT correlated with Fiebig stages III to V (p = 0.001) and baseline HIV RNA >6 log10 copies/mL (p = 0.012). Baseline elevations resolved by 48 weeks on ART in 59 of the 66 individuals (89%). ALT elevations at 24 and 48 weeks correlated with Fiebig stages I to II at diagnosis (p < 0.001), baseline plasma HIV RNA levels <6 log10 copies/mL (p < 0.001), abnormal baseline ALT (p < 0.001), baseline CD4 >350 cells/?L (p = 0.03) and older age (p = 0.03). Individuals initiating efavirenz-based regimens were more likely to have elevated ALT levels at 48 weeks compared with those on non-efavirenz-based regimens (p = 0.003). CONCLUSIONS:One in six people with acute HIV infection have elevated LFTs. Clinical outcomes with ART started in acute HIV are generally good, with resolution of ALT elevations within 48 weeks on ART in most cases. These results suggest a multifactorial model for hepatic injury involving a combination of HIV-associated and ART-associated processes, which may change over time.
| S-EPMC6968973 | biostudies-literature
Project description:ObjectivesSARS-CoV-2 can cause respiratory diseases with various manifestations. However, little is known about its potential for lung recovery. Lung ultrasound has shown characteristic changes during COVID-19 and has proven to be useful for triage, diagnosis, and therapy. This study investigated how the recovery process from COVID-19 respiratory disease can be monitored using 12-zone lung ultrasound.MethodsThis prospective observational cohort study was conducted in a busy urban emergency department in London, United Kingdom, over a 20-week period between April and October 2020. We followed 24 patients recovering from COVID-19 with varying disease severity using 12-zone lung ultrasound at 2-week intervals and monitored the changes in the prevalence of lung abnormalities previously described in COVID-19 infection (irregular pleura, subpleural consolidation, B-lines, and small localized effusions).ResultsLung ultrasound showed that the lung recovers significantly over 20 weeks postdisease. Individual lung abnormalities also resolved at different rates. The entire rib space occupied by confluent B-lines wane after the acute phase, whereas irregular pleura and subpleural consolidations resolved more gradually. Separate wide B-lines moving with the pleura during respiration may represent more stable features, indicating residual fibrotic changes. Small, localized effusions appear transiently after the initial acute phase of the disease, peaking at approximately 10 weeks after infection. The measured lung abnormalities were strong predictors of perceived shortness of breath during ambulation.ConclusionLung ultrasound can be a useful tool for long-term monitoring of COVID-19 lung disease, avoiding repeated exposure to ionizing radiation, and may distinguish between acute and past infections.
| S-EPMC9088416 | biostudies-literature
Project description:Background: Several studies using bronchoalveolar lavage fluid (BALF) reported that lung microbial communities were associated with the development and clinical outcome of idiopathic pulmonary fibrosis (IPF). However, the microbial communities in IPF lung tissues are not well known. This study is aimed to investigate bacterial microbial communities in lung tissues and determine their impact on the clinical outcomes of patients with IPF. Methods: Genomic DNA extracted from lung tissues of patients with IPF (n = 20; 10 non-survivors) and age- and sex-matched controls (n = 20) was amplified using fusion primers targeting the V3 and V4 regions of the 16S RNA genes with indexing barcodes. Results: Mean age of IPF subjects was 63.3 yr, and 65% were male. Alpha diversity indices did not significantly differ between IPF patients and controls, or between IPF non-survivors and survivors. The relative abundance of Lactobacillus, Paracoccus, and Akkermansia was increased, whereas that of Caulobacter, Azonexus, and Undibacterium decreased in patients with IPF compared with that in the controls. A decreased relative abundance of Pelomonas (odds ratio [OR], 0.352, p = 0.027) and Azonexus (OR, 0.013, p = 0.046) was associated with a diagnosis of IPF in the multivariable logistic analysis adjusted by age and gender. Multivariable Cox analysis adjusted for age and forced vital capacity (FVC) revealed that higher relative abundance of Streptococcus (hazard ratio [HR], 1.993, p = 0.044), Sphingomonas (HR, 57.590, p = 0.024), and Clostridium (HR, 37.189, p = 0.038) was independently associated with IPF mortality. The relative abundance of Curvibacter (r = 0.590) and Thioprofundum (r = 0.373) was correlated positively, whereas that of Anoxybacillus (r = -0.509) and Enterococcus (r = -0.593) was correlated inversely with FVC. In addition, the relative abundance of the Aquabacterium (r = 0.616) and Peptoniphilus (r = 0.606) genera was positively correlated, whereas that of the Fusobacterium (r = -0.464) and Phycicoccus (r = -0.495) genera was inversely correlated with distance during the 6-min walking test. Conclusions: The composition of the microbiome in lung tissues differed between patients with IPF and controls and was associated with the diagnosis, mortality, and disease severity of IPF.
| S-EPMC8559550 | biostudies-literature
Project description:Gut microbiota in HIV-pneumonia patients is related to peripheral CD4 counts, lung microbiota and in vitro macrophage dysfunction
| PRJEB29534 | ENA
Project description:Evidence indicates that the microbiome plays a significant role in HIV immunopathogenesis and associated complications. This study aimed to characterize the oral and anal microbiome of Men who have Sex with Men (MSM) and Transgender Women (TGW), with and without HIV. One hundred and thirty oral and anal DNA-derived samples were obtained from 78 participants and subjected to shotgun metagenomics sequencing for further microbiome analysis. Significant differences in the microbiome composition were found among subjects associated with HIV infection, gender, sex behavior, CD4+ T-cell counts, antiretroviral therapy (ART), and the presence of HPV-associated precancerous anal lesions. Results confirm the occurrence of oncogenic viromes in this high HIV-risk population. The oral microbiome in HIV-associated cases exhibited an enrichment of bacteria associated with periodontal disease pathogenesis. Conversely, anal bacteria showed a significant decrease in HIV-infected subjects (Coprococcus comes, Finegoldia magna, Blautia obeum, Catenibacterium mitsuokai). TGW showed enrichment in species related to sexual transmission, which concurs that most recruited TGW are or have been sex workers. Prevotella bivia and Fusobacterium gonidiaformans were positively associated with anal precancerous lesions among HIV-infected subjects. The enrichment of Holdemanella biformis and C. comes was associated with detectable viral load and ART-untreated patients. Metabolic pathways were distinctly affected by predominant factors linked to sexual behavior or HIV pathogenesis. Gene family analysis identified bacterial gene signatures as potential prognostic and predictive biomarkers for HIV/AIDS-associated malignancies. Conclusions: Identified microbial features at accessible sites are potential biomarkers for predicting precancerous anal lesions and therapeutic targets for HIV immunopathogenesis.
| S-EPMC10338440 | biostudies-literature