HIV-Positive Patients on Antiretroviral Therapy Have an Altered Mucosal Intestinal but Not Oral Microbiome

From BugSigDB
Reviewed Marked as Reviewed by Svetlana up on 2024-5-28
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Meng J, Tao J, Abu Y, Sussman DA, Girotra M, Franceschi D, Roy S
Journal
Microbiology spectrum
Year
2023
Keywords:
16S RNA, HIV, antiretroviral therapy, human microbiome, intestinal microbiome, oral microbiome
This study characterized compositional and functional shifts in the intestinal and oral microbiome in HIV-positive patients on antiretroviral therapy compared to HIV-negative individuals. Seventy-nine specimens were collected from 5 HIV-positive and 12 control subjects from five locations (colon brush, colon wash, terminal ileum [TI] brush, TI wash, and saliva) during colonoscopy and at patient visits. Microbiome composition was characterized using 16S rRNA sequencing, and microbiome function was predicted using bioinformatics tools (PICRUSt and BugBase). Our analysis indicated that the β-diversity of all intestinal samples (colon brush, colon wash, TI brush, and TI wash) from patients with HIV was significantly different from patients without HIV. Specifically, bacteria from genera Prevotella, Fusobacterium, and Megasphaera were more abundant in samples from HIV-positive patients. On the other hand, bacteria from genera Ruminococcus, Blautia, and Clostridium were more abundant in samples from HIV-negative patients. Additionally, HIV-positive patients had higher abundances of biofilm-forming and pathogenic bacteria. Furthermore, pathways related to translation and nucleotide metabolism were elevated in HIV-positive patients, whereas pathways related to lipid and carbohydrate metabolism were positively correlated with samples from HIV-negative patients. Our analyses further showed variations in microbiome composition in HIV-positive and negative patients by sampling site. Samples from colon wash, colon brush, and TI wash were significant between groups, while samples from TI brush and saliva were not significant. Taken together, here, we report altered intestinal microbiome composition and predicted function in patients with HIV compared to uninfected patients, though we found no changes in the oral microbiome. IMPORTANCE Over 37 million people worldwide are living with HIV. Although the availability of antiretroviral therapy has significantly reduced the number of AIDS-related deaths, individuals living with HIV are at increased risk for opportunistic infections. We now know that HIV interacts with the trillions of bacteria, fungi, and viruses in the human body termed the microbiome. Only a limited number of previous studies have compared variations in the oral and gastrointestinal microbiome with HIV infection. Here, we detail how the oral and gastrointestinal microbiome changes with HIV infection, having used 5 different sampling sites to gain a more comprehensive view of these changes by location. Our results show site-specific changes in the intestinal microbiome associated with HIV infection. Additionally, we show that while there were significant changes in the intestinal microbiome, there were no significant changes in the oral microbiome.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-5-28

Curated date: 2024/03/14

Curator: Eve10111

Revision editor(s): Eve10111, Scholastica

Subjects

Location of subjects
United States of America
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
Ileum , Colon Distal intestine,Intestinum ileum,Lower intestine,Posterior intestine,Ileum,ileum,Hindgut,Large bowel,Colon,colon
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to antiviral drug Response to antiviral drug,response to antiviral drug
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Intestinal samples of Healthy Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Intestinal samples of HIV Positive Patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
All intestinal samples (colon brush, colon wash, terminal ileum brush, and terminal ileum wash) of HIV-positive individuals on antiretroviral therapy
Group 0 sample size Number of subjects in the control (unexposed) group
12
Group 1 sample size Number of subjects in the case (exposed) group
5
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
30 days

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
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
2

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-5-28

Curated date: 2024/03/14

Curator: Eve10111

Revision editor(s): Eve10111, Scholastica

Source: Fig. 1C

Description: Linear discriminant analysis effect size (LEfSe) analysis of top discriminative bacteria genera between gut samples from HIV-positive compared to HIV-negative patients.

Abundance in Group 1: increased abundance in Intestinal samples of HIV Positive Patients

NCBI Quality ControlLinks
Akkermansia
Collinsella
Eubacterium
Fusobacterium
Megasphaera
Mitsuokella
Mogibacterium
Peptostreptococcus
Phascolarctobacterium
Prevotella
Succinivibrio
Methanobrevibacter

Revision editor(s): Eve10111, Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-5-28

Curated date: 2024/03/14

Curator: Eve10111

Revision editor(s): Eve10111, Scholastica

Source: Fig. 1C

Description: Linear discriminant analysis effect size (LEfSe) analysis of top discriminative bacteria genera between gut samples from HIV-positive compared to HIV-negative patients.

Abundance in Group 1: decreased abundance in Intestinal samples of HIV Positive Patients

NCBI Quality ControlLinks
Blautia
Clostridium
Ruminococcus

Revision editor(s): Eve10111, Scholastica

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-5-28

Curated date: 2024/05/27

Curator: Scholastica

Revision editor(s): Scholastica

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Colon Hindgut,Large bowel,Posterior intestine,Colon,colon
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Colon wash samples of Healthy Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Colon wash samples of HIV Positive Patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Colon wash samples of HIV-positive individuals on antiretroviral therapy

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-5-28

Curated date: 2024/05/27

Curator: Scholastica

Revision editor(s): Scholastica

Source: Fig. 3C

Description: Linear discriminant analysis effect size (LEfSe) analysis of top discriminative bacteria genera between colon wash samples from HIV-positive compared to HIV-negative patients.

Abundance in Group 1: increased abundance in Colon wash samples of HIV Positive Patients

NCBI Quality ControlLinks
Succinivibrio
Aggregatibacter

Revision editor(s): Scholastica

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-5-28

Curated date: 2024/05/27

Curator: Scholastica

Revision editor(s): Scholastica

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Colon brush samples of Healthy Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Colon brush samples of HIV Positive Patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Colon brush samples of HIV-positive individuals on antiretroviral therapy

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-5-28

Curated date: 2024/05/27

Curator: Scholastica

Revision editor(s): Scholastica

Source: Fig. 4C

Description: Linear discriminant analysis effect size (LEfSe) analysis of top discriminative bacteria genera between colon brush samples from HIV-positive compared to HIV-negative patients.

Abundance in Group 1: increased abundance in Colon brush samples of HIV Positive Patients

NCBI Quality ControlLinks
Megasphaera
Slackia

Revision editor(s): Scholastica

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2024-5-28

Curated date: 2024/05/27

Curator: Scholastica

Revision editor(s): Scholastica

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Ileum Distal intestine,Intestinum ileum,Lower intestine,Posterior intestine,Ileum,ileum
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Terminal ileum wash samples of Healthy Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Terminal ileum wash samples of HIV Positive Patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Terminal ileum (TI) wash samples of HIV-positive individuals on antiretroviral therapy

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-5-28

Curated date: 2024/05/27

Curator: Scholastica

Revision editor(s): Scholastica

Source: Fig. 5C

Description: Linear discriminant analysis effect size (LEfSe) analysis of top discriminative bacteria genera between terminal ileum (TI) samples from HIV-positive compared to HIV-negative patients.

Abundance in Group 1: increased abundance in Terminal ileum wash samples of HIV Positive Patients

NCBI Quality ControlLinks
Prevotella
Mogibacterium
Mitsuokella
Aggregatibacter

Revision editor(s): Scholastica