Sputum Microbiome and Chronic Obstructive Pulmonary Disease in a Rural Ugandan Cohort of Well-Controlled HIV Infection
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
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
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).
- raw counts
- 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
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
Revision editor(s): Chinelsy, ChiomaBlessing
Signature 2
Reviewed Marked as Reviewed by Chinelsy on 2023-10-30
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
Revision editor(s): Chinelsy, ChiomaBlessing, Welile
Experiment 2
Reviewed Marked as Reviewed by Chinelsy on 2023-10-30
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
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)
Revision editor(s): Chinelsy, ChiomaBlessing, Welile
Signature 2
Reviewed Marked as Reviewed by Chinelsy on 2023-10-30
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)
Revision editor(s): Chinelsy, ChiomaBlessing
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