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

Study information

Needs review

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

36511710

DOI Digital object identifier for electronic documents.

https://doi.org/10.1128/spectrum.02472-22

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

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Curated date: 2024/03/14

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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: Saliva , Mouth mucosa , Intestinal brush border layer Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva,Buccal mucosa,Mouth mucosa,Mouth mucous membrane,Mouth organ mucosa,Mucosa of mouth,Mucosal lining of mouth,Mucous membrane of mouth,Oral mucosa,Oral mucous membrane,Oral part of viscerocranial mucosa,Tunica mucosa oris,mouth mucosa,Brush border microvillus layer of intestine,Intestinal brush border,Intestinal brush border layer,intestinal brush border layer

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: HIV enteropathy HIV Enteropathy,HIV enteropathy,hIV enteropathy

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy Control

Group 1 name Corresponds to the case (exposed) group for case-control studies: HIV Positive Patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: compositional and functional shifts in the intestinal and oral microbiome in HIV-positive patients on antiretroviral therapy compared to HIV-negative individuals

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): N/A

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4-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: Kruskall-Wallis; PERMANOVA; 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: 3

Matched on Factors on which subjects have been matched on in a case-control study: age, sex, Matched on: "Hispanic" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Hispanic, Matched on: "Non-Hispanic" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Non-Hispanic

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

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Source: fig.S1

Description: Bacterial composition at phylum and genus levels in the gut samples, Linear discriminant analysis (LDA) effect size (LEfSe) analysis was performed among intestinal samples to determine the bacterial taxa that were differentially enriched. Bacteria from the genera were more abundant in samples from HIV-positive patients.

Abundance in Group 1: increased abundance in HIV Positive Patients

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Prevotella
Fusobacterium
Eubacterium
Collinsella
Megasphaera
Mogibacterium
Mitsuokella

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Signature 2

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Source: fig.S1

Description: Bacterial composition at phylum and genus levels in the gut samples, Linear discriminant analysis (LDA) effect size (LEfSe) analysis was performed among intestinal samples to determine the bacterial taxa that were differentially enriched. Bacteria from the genera were more abundant in samples from HIV-positive patients.

Abundance in Group 1: decreased abundance in HIV Positive Patients

NCBI	Quality Control	Links
Ruminococcus
Blautia
Clostridium

Revision editor(s): Eve10111