Sputum Microbiome and Chronic Obstructive Pulmonary Disease in a Rural Ugandan Cohort of Well-Controlled HIV Infection

From BugSigDB
Reviewed Marked as Reviewed by Chinelsy on 2023-10-30
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Kayongo A, Bartolomaeus TUP, Birkner T, Markó L, Löber U, Kigozi E, Atugonza C, Munana R, Mawanda D, Sekibira R, Uwimaana E, Alupo P, Kalyesubula R, Knauf F, Siddharthan T, Bagaya BS, Kateete DP, Joloba ML, Sewankambo NK, Jjingo D, Kirenga B, Checkley W, Forslund SK
Journal
Microbiology spectrum
Year
2023
Keywords:
AIDS, COPD, HIV, HIV-associated COPD, airway, airway microbiome, human immunodeficiency virus, microbiome, sputum
Sub-Saharan Africa has increased morbidity and mortality related to chronic obstructive pulmonary disease (COPD). COPD among people living with HIV (PLWH) has not been well studied in this region, where HIV/AIDS is endemic. Increasing evidence suggests that respiratory microbial composition plays a role in COPD severity. Therefore, we aimed to investigate microbiome patterns and associations among PLWH with COPD in Sub-Saharan Africa. We conducted a cross-sectional study of 200 adults stratified by HIV and COPD in rural Uganda. Induced sputum samples were collected as an easy-to-obtain proxy for the lower respiratory tract microbiota. We performed 16S rRNA gene sequencing and used PICRUSt2 (version 2.2.3) to infer the functional profiles of the microbial community. We used a statistical tool to detect changes in specific taxa that searches and adjusts for confounding factors such as antiretroviral therapy (ART), age, sex, and other participant characteristics. We could cluster the microbial community into three community types whose distribution was shown to be significantly impacted by HIV. Some genera, e.g., Veillonella, Actinomyces, Atopobium, and Filifactor, were significantly enriched in HIV-infected individuals, while the COPD status was significantly associated with Gammaproteobacteria and Selenomonas abundance. Furthermore, reduced bacterial richness and significant enrichment in Campylobacter were associated with HIV-COPD comorbidity. Functional prediction using PICRUSt2 revealed a significant depletion in glutamate degradation capacity pathways in HIV-positive patients. A comparison of our findings with an HIV cohort from the United Kingdom revealed significant differences in the sputum microbiome composition, irrespective of viral suppression. IMPORTANCE Even with ART available, HIV-infected individuals are at high risk of suffering comorbidities, as shown by the high prevalence of noninfectious lung diseases in the HIV population. Recent studies have suggested a role for the respiratory microbiota in driving chronic lung inflammation. The respiratory microbiota was significantly altered among PLWH, with disease persisting up to 3 years post-ART initiation and HIV suppression. The community structure and diversity of the sputum microbiota in COPD are associated with disease severity and clinical outcomes, both in stable COPD and during exacerbations. Therefore, a better understanding of the sputum microbiome among PLWH could improve COPD prognostic and risk stratification strategies. In this study, we observed that in a virologically suppressed HIV cohort in rural Uganda, we could show differences in sputum microbiota stratified by HIV and COPD, reduced bacterial richness, and significant enrichment in Campylobacter associated with HIV-COPD comorbidity.

Experiment 1


Reviewed Marked as Reviewed by Chinelsy on 2023-10-30

Curated date: 2023/10/07

Curator: Shakira

Revision editor(s): Shakira, Chinelsy

Subjects

Location of subjects
Uganda
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
Chronic obstructive pulmonary disease Airflow Obstruction, Chronic,Airflow Obstructions, Chronic,CAFL - Chronic airflow limitation,CAL - Chronic airflow limitation,CAO - Chronic airflow obstruction,Chronic airflow limitation,Chronic Airflow Obstruction,Chronic Airflow Obstructions,Chronic airway disease,Chronic airway obstruction,chronic airway obstruction, NEC in ICD9CM_2006,chronic airway obstruction, not elsewhere classified,Chronic irreversible airway obstruction,CHRONIC OBSTRUCTIVE AIRWAY DIS,chronic obstructive airway disease,Chronic Obstructive Airways Disease,chronic obstructive airways disease,chronic obstructive airways disease NOS,chronic obstructive airways disease NOS (disorder),CHRONIC OBSTRUCTIVE LUNG DIS,Chronic Obstructive Lung Disease,chronic obstructive lung disease,chronic obstructive lung disease (disorder),chronic obstructive lung disease [Ambiguous],Chronic obstructive lung disease, NEC,Chronic obstructive lung disease, NOS,CHRONIC OBSTRUCTIVE PULM DIS,chronic obstructive pulmonary disease,Chronic Obstructive Pulmonary Disease (COPD),chronic obstructive pulmonary disease (COPD),chronic obstructive pulmonary disease and allied conditions,Chronic obstructive pulmonary disease finding,Chronic obstructive pulmonary disease finding (finding),Chronic obstructive pulmonary disease NOS,CHRONIC OBSTRUCTIVE PULMONARY DISEASE, (COPD),chronic obstructive pulmonary disease, (COPD),COAD,COAD - Chronic obstructive airways disease,COLD,cold,COLD (chronic obstructive lung disease),cold (chronic obstructive lung disease),COLD - Chronic obstructive lung disease,COPD,COPD - Chronic obstructive pulmonary disease,COPD NOS,COPD, CHRONIC OBSTRUCTIVE PULMONARY DISEASE,COPD, chronic obstructive pulmonary disease,DISEASE (COPD), CHRONIC OBSTRUCTIVE,disease (COPD), chronic obstructive,Dops,obstructive lung disease, chronic,OBSTRUCTIVE PULMONARY DISEASE (COPD), CHRONIC,obstructive pulmonary disease (COPD), chronic,PULM DIS CHRONIC OBSTRUCTIVE,PULMONARY DISEASE (COPD), CHRONIC OBSTRUCTIVE,pulmonary disease (COPD), chronic obstructive,Pulmonary Disease, Chronic Obstructive,Chronic obstructive pulmonary disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
HIV-negative individuals with COPD
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV-positive individuals diagnosed with COPD
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The exposed group (Group 1) consists of individuals with both HIV infection and COPD.
Group 0 sample size Number of subjects in the control (unexposed) group
50
Group 1 sample size Number of subjects in the case (exposed) group
50
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Antibiotic use within 2 weeks

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
Linear Regression
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
Matched on Factors on which subjects have been matched on in a case-control study
age, sex, smoking status

Alpha Diversity

Pielou Quantifies how equal the community is numerically
increased
Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
increased

Signature 1

Reviewed Marked as Reviewed by Chinelsy on 2023-10-30

Curated date: 2023/10/27

Curator: Chinelsy

Revision editor(s): Chinelsy, ChiomaBlessing

Source: Table 4.

Description: Mean relative abundance of phyla and genera in HIV-positive individuals diagnosed with COPD versus HIV-negative individuals with COPD

Abundance in Group 1: increased abundance in HIV-positive individuals diagnosed with COPD

NCBI Quality ControlLinks
Actinomycetota
Aggregatibacter
Arachnia
Bacillota
Bacillus
Candidatus Saccharibacteria bacterium
Cardiobacterium
Corynebacterium
Eubacterium
Filifactor
Fusobacterium
Gemella
Lentimicrobium
Leptotrichia
Limosilactobacillus
Moraxella
Parvimonas
Prevotella
Propionibacterium
Pseudomonadota
Rothia
Selenomonas
Spirochaetota
Streptococcus
Synergistota
Tannerella
bacterium
uncultured Candidatus Saccharibacteria bacterium
unidentified proteobacterium
Rikenellaceae RC9Rikenellaceae RC9
unknown Bacteroidotaunknown Bacteroidota
unknown Clostridiaunknown Clostridia
unknown Negativicutesunknown Negativicutes
unknown Firmicutesunknown Firmicutes
unknown Leptotrichiaceaeunknown Leptotrichiaceae
unknown Neisseriaceaeunknown Neisseriaceae
unknown Spirochaetalesunknown Spirochaetales
Eubacterium sp.

Revision editor(s): Chinelsy, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Chinelsy on 2023-10-30

Curated date: 2023/10/27

Curator: Chinelsy

Revision editor(s): Chinelsy, ChiomaBlessing, Welile

Source: Table 4.

Description: Mean relative abundance of phyla and genera in HIV-positive individuals diagnosed with COPD versus HIV-negative individuals with COPD

Abundance in Group 1: decreased abundance in HIV-positive individuals diagnosed with COPD

NCBI Quality ControlLinks
Abiotrophia
Acholeplasma
Actinobacillus
Actinomyces
Alloprevotella
Anaeroglobus
Atopobium
Bacteroidota
Bergeyella
Campylobacter
Campylobacterota
Candidatus Saccharimonas
Capnocytophaga
Dialister
Eubacterium sp.
Fretibacterium
Fusobacteriota
Granulicatella
Haemophilus
Lachnoanaerobaculum
Lautropia
Neisseria
Oribacterium
Patescibacteria group
Peptococcus
Peptostreptococcus
Porphyromonas
Prevotella sp.
Selenomonadales
Simonsiella
Solobacterium
Stomatobaculum
Streptobacillus
Tannerella
Treponema
Veillonella
unclassified Bacilli
unclassified Bacteroidales
unclassified Bacteroidia
unclassified Candidatus Gracilibacteria
unclassified Candidatus Saccharimonadales
unclassified Candidatus Saccharimonadia
unclassified Erysipelotrichaceae
unclassified Gammaproteobacteria
unclassified Lachnospiraceae
unclassified Prevotellaceae
unclassified Veillonellaceae
uncultured Clostridia bacterium
uncultured actinomycete
Candidatus Nanosynbacter lyticus

Revision editor(s): Chinelsy, ChiomaBlessing, Welile

Experiment 2


Reviewed Marked as Reviewed by Chinelsy on 2023-10-30

Curated date: 2023/10/27

Curator: Chinelsy

Revision editor(s): Chinelsy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
HIV-negative individuals (without COPD)
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV-positive individuals (without COPD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The exposed group (Group 1) consists of individuals with HIV infection but without COPD.

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
increased
Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
increased

Signature 1

Reviewed Marked as Reviewed by Chinelsy on 2023-10-30

Curated date: 2023/10/28

Curator: Chinelsy

Revision editor(s): Chinelsy, ChiomaBlessing, Welile

Source: Table 4.

Description: Mean relative abundance of phyla and genera in HIV-positive individuals without COPD versus HIV-negative individuals without COPD

Abundance in Group 1: increased abundance in HIV-positive individuals (without COPD)

NCBI Quality ControlLinks
Actinobacillus
Actinomyces
Actinomycetota
Alloprevotella
Aminipila
Atopobium
Bacillus
Bacteroidota
Butyrivibrio
Campylobacter
Campylobacterota
Candidatus Saccharimonas
Capnocytophaga
Catonella
Corynebacterium
Cyanobacteriota
Eubacterium
Fusobacteriales
Gemella
Granulicatella
Haemophilus
Lachnoanaerobaculum
Moraxella
Oribacterium
Patescibacteria group
Peptoanaerobacter
Porphyromonas
Prevotella sp.
Propionibacterium
Pseudomonadota
Selenomonadaceae
Selenomonadales
Selenomonas
Solobacterium
Spirochaetota
Stomatobaculum
Streptobacillus
Synergistota
Treponema
Veillonella
uncultured Candidatus Saccharibacteria bacterium
uncultured actinomycete
unknown Prevotellaceaeunknown Prevotellaceae
unknown Bacteroidalesunknown Bacteroidales
unknown Bacteroidiaunknown Bacteroidia
unknown Erysipelotrichaceaeunknown Erysipelotrichaceae
unknown Bacilliunknown Bacilli
unknown Lachnospiraceaeunknown Lachnospiraceae
unknown Clostridiaunknown Clostridia
unknown Veillonellaceaeunknown Veillonellaceae
unknown Saccharimonadalesunknown Saccharimonadales
unknown Saccharimonadiaunknown Saccharimonadia
unknown Gammaproteobacteriaunknown Gammaproteobacteria
Candidatus Nanosynbacter lyticus

Revision editor(s): Chinelsy, ChiomaBlessing, Welile

Signature 2

Reviewed Marked as Reviewed by Chinelsy on 2023-10-30

Curated date: 2023/10/28

Curator: Chinelsy

Revision editor(s): Chinelsy, ChiomaBlessing

Source: Table 4.

Description: Mean relative abundance of phyla and genera in HIV-positive individuals without COPD versus HIV-negative individuals without COPD

Abundance in Group 1: decreased abundance in HIV-positive individuals (without COPD)

NCBI Quality ControlLinks
Abiotrophia
Aggregatibacter
Arachnia
Bacillota
Candidatus Saccharibacteria bacterium
Filifactor
Fretibacterium
Fusobacteriota
Fusobacterium
Lautropia
Leptotrichia
Neisseria
Parvimonas
Peptostreptococcus
Prevotella
Rothia
Streptococcus
unknown Actinomycetaceaeunknown Actinomycetaceae
unknown Bacteroidotaunknown Bacteroidota
unknown Staphylococcalesunknown Staphylococcales
unknown Negativicutesunknown Negativicutes
unknown Firmicutesunknown Firmicutes
unknown Leptotrichiaceaeunknown Leptotrichiaceae
Eubacterium sp.

Revision editor(s): Chinelsy, ChiomaBlessing