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Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant.

ABSTRACT: Long-term survival after lung transplantation is limited by infectious complications and by bronchiolitis obliterans syndrome (BOS), a form of chronic rejection linked in part to microbial triggers.To define microbial populations in the respiratory tract of transplant patients comprehensively using unbiased high-density sequencing.Lung was sampled by bronchoalveolar lavage (BAL) and upper respiratory tract by oropharyngeal wash (OW). Bacterial 16S rDNA and fungal internal transcribed spacer sequencing was used to profile organisms present. Outlier analysis plots defining taxa enriched in lung relative to OW were used to identify bacteria enriched in lung against a background of oropharyngeal carryover.Lung transplant recipients had higher bacterial burden in BAL than control subjects, frequent appearance of dominant organisms, greater distance between communities in BAL and OW indicating more distinct populations, and decreased respiratory tract microbial richness and diversity. Fungal populations were typically dominated by Candida in both sites or by Aspergillus in BAL but not OW. 16S outlier analysis identified lung-enriched taxa indicating bacteria replicating in the lower respiratory tract. In some cases this confirmed respiratory cultures but in others revealed enrichment by anaerobic organisms or mixed outgrowth of upper respiratory flora and provided quantitative data on relative abundances of bacteria found by culture.Respiratory tract microbial communities in lung transplant recipients differ in structure and composition from healthy subjects. Outlier analysis can identify specific bacteria replicating in lung. These findings provide novel approaches to address the relationship between microbial communities and transplant outcome and aid in assessing lung infections.

SUBMITTER: Charlson ES

PROVIDER: S-EPMC3480531 | biostudies-other | 2012 Sep

REPOSITORIES: biostudies-other

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Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant.

Charlson Emily S ES Diamond Joshua M JM Bittinger Kyle K Fitzgerald Ayannah S AS Yadav Anjana A Haas Andrew R AR Bushman Frederic D FD Collman Ronald G RG

American journal of respiratory and critical care medicine 20120712 6

<h4>Rationale</h4>Long-term survival after lung transplantation is limited by infectious complications and by bronchiolitis obliterans syndrome (BOS), a form of chronic rejection linked in part to microbial triggers.<h4>Objectives</h4>To define microbial populations in the respiratory tract of transplant patients comprehensively using unbiased high-density sequencing.<h4>Methods</h4>Lung was sampled by bronchoalveolar lavage (BAL) and upper respiratory tract by oropharyngeal wash (OW). Bacterial ...[more]

PMID: 22798321

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Project description:Introduction: Childhood growth is a sensitive marker of health. Animal studies show increased height and weight velocity in the presence of fungal as well as antibiotic supplement in feed. Human studies on early gut microbiota and anthropometrics have mainly focused on bacteria only and overweight, with diverging results. We thus aimed to investigate the associations between childhood growth [height and body mass index (BMI)] and early fungal and bacterial gut microbiota. Methods: In a population-based cohort, a subset of 278 pregnant mothers was randomized to drink milk with or without probiotic bacteria during and after pregnancy. We obtained fecal samples in offspring at four time points between 0 and 2 years and anthropometric measurements 0 and 9 years. By quantitative PCR and 16S/ITS rRNA gene sequencing, children's gut microbiota abundance and diversity were analyzed against height standard deviation score (SDS) and BMI-SDS and presented as effect estimate (β) of linear mixed models. Results: From 278 included children (149 girls), 1,015 fecal samples were collected. Maternal probiotic administration did not affect childhood growth, and the groups were pooled. Fungal abundance at 2 years was positively associated with height-SDS at 2-9 years (β = 0.11 height-SDS; 95% CI, 0.00, 0.22) but not with BMI-SDS. Also, higher fungal abundance at 1 year was associated with a lower BMI-SDS at 0-1 year (β = -0.09 BMI-SDS; 95% CI, -0.18, -0.00), and both bacterial abundance and bacterial alpha diversity at 1 year were associated with lower BMI-SDS at 0-1 year (β = -0.13 BMI-SDS; 95% CI, -0.22, -0.04; and β = -0.19 BMI-SDS; 95% CI, -0.39, -0.00, respectively). Conclusions: In this prospective cohort following 0-9-year-old children, we observed that higher gut fungal abundances at 2 years were associated with taller children between 2 and 9 years. Also, higher gut fungal and bacterial abundances and higher gut bacterial diversity at 1 year were associated with lower BMI in the first year of life. The results may indicate interactions between early gut fungal microbiota and the human growth-regulating physiology, previously not reported. Clinical Trial Registration: Clinicaltrials.gov, NCT00159523.

Dataset Information

Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant.

Publications

Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant.

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