The Airway Microbiota Signatures of Infection and Rejection in Lung Transplant Recipients

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Reviewed Marked as Reviewed by Peace Sandy on 2024-4-9
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Su J, Li CX, Liu HY, Lian QY, Chen A, You ZX, Li K, Cai YH, Lin YX, Pan JB, Zhang GX, Ju CR, You CX, He JX
Journal
Microbiology spectrum
Year
2022
Keywords:
16S rRNA, airway microbiota, infection, lung transplant, rejection
Infection and rejection are the two most common complications after lung transplantation (LT) and are associated with increased morbidity and mortality. We aimed to examine the association between the airway microbiota and infection and rejection in lung transplant recipients (LTRs). Here, we collected 181 sputum samples (event-free, n = 47; infection, n = 103; rejection, n = 31) from 59 LTRs, and performed 16S rRNA gene sequencing to analyze the airway microbiota. A significantly different airway microbiota was observed among event-free, infection and rejection recipients, including microbial diversity and community composition. Nineteen differential taxa were identified by linear discriminant analysis (LDA) effect size (LEfSe), with 6 bacterial genera, Actinomyces, Rothia, Abiotrophia, Neisseria, Prevotella, and Leptotrichia enriched in LTRs with rejection. Random forest analyses indicated that the combination of the 6 genera and procalcitonin (PCT) and T-lymphocyte levels showed area under the curve (AUC) values of 0.898, 0.919 and 0.895 to differentiate between event-free and infection recipients, event-free and rejection recipients, and infection and rejection recipients, respectively. In conclusion, our study compared the airway microbiota between LTRs with infection and acute rejection. The airway microbiota, especially combined with PCT and T-lymphocyte levels, showed satisfactory predictive efficiency in discriminating among clinically stable recipients and those with infection and acute rejection, suggesting that the airway microbiota can be a potential indicator to differentiate between infection and acute rejection after LT. IMPORTANCE Survival after LT is limited compared with other solid organ transplantations mainly due to infection- and rejection-related complications. Differentiating infection from rejection is one of the most important challenges to face after LT. Recently, the airway microbiota has been reported to be associated with either infection or rejection of LTRs. However, fewer studies have investigated the relationship between airway microbiota together with infection and rejection of LTRs. Here, we conducted an airway microbial study of LTRs and analyzed the airway microbiota together with infection, acute rejection, and clinically stable recipients. We found different airway microbiota between infection and acute rejection and identify several genera associated with each outcome and constructed a model that incorporates airway microbiota and clinical parameters to predict outcome. This study highlighted that the airway microbiota was a potential indicator to differentiate between infection and acute rejection after LT.

Experiment 1


Reviewed Marked as Reviewed by Peace Sandy on 2024-4-9

Curated date: 2024/03/20

Curator: Sidrakhan

Revision editor(s): Sidrakhan, Scholastica

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Sputum Expectoration,Sputum,sputum
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Lung transplantation lung transplant,transplant of lung,transplantation of lung,Lung transplantation,lung transplantation
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Clinically stable (or event-free) recipients
Group 1 name Corresponds to the case (exposed) group for case-control studies
Recipients with infection
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Lung transplant recipients (LTRs) with infection
Group 0 sample size Number of subjects in the control (unexposed) group
47
Group 1 sample size Number of subjects in the case (exposed) group
103
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
4

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2024-4-9

Curated date: 2024/03/20

Curator: Sidrakhan

Revision editor(s): Sidrakhan, Scholastica

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Recipients with rejection
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Lung transplant recipients (LTRs) with rejection
Group 1 sample size Number of subjects in the case (exposed) group
31

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased

Signature 1

Needs review

Curated date: 2024/03/26

Curator: Scholastica

Revision editor(s): Scholastica

Source: Fig. 4C

Description: LEfSe analysis identifying the airway microbiota that were differentially altered among the transplant groups. Only those taxa with LDA scores 4.0 were ultimately considered.

Abundance in Group 1: increased abundance in Recipients with rejection

NCBI Quality ControlLinks
Actinomycetota
Micrococcaceae
Micrococcales
Rothia
Aerococcaceae
Abiotrophia
Neisseriaceae
Neisseria
BetaproteobacterialesBetaproteobacteriales
Actinomyces
Prevotella_7Prevotella_7
Actinomycetales
Actinomycetaceae
Fusobacteriales
Leptotrichia
Fusobacteriia
Leptotrichiaceae

Revision editor(s): Scholastica

Experiment 3


Reviewed Marked as Reviewed by Peace Sandy on 2024-4-9

Curated date: 2024/03/20

Curator: Sidrakhan

Revision editor(s): Sidrakhan, Scholastica

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Recipients with infection
Group 0 sample size Number of subjects in the control (unexposed) group
103

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased

Signature 1

Needs review

Curated date: 2024/03/26

Curator: Scholastica

Revision editor(s): Scholastica

Source: Fig. 4C

Description: LEfSe analysis identifying the airway microbiota that were differentially altered among the transplant groups. Only those taxa with LDA scores 4.0 were ultimately considered.

Abundance in Group 1: increased abundance in Recipients with rejection

NCBI Quality ControlLinks
Abiotrophia
Actinomyces
Actinomycetaceae
Actinomycetales
Actinomycetota
Aerococcaceae
Fusobacteriales
Fusobacteriia
Leptotrichia
Leptotrichiaceae
Micrococcaceae
Micrococcales
Neisseria
Neisseriaceae
Rothia
BetaproteobacterialesBetaproteobacteriales
Prevotella_7Prevotella_7

Revision editor(s): Scholastica