Unique Gut Microbiome in HIV Patients on Antiretroviral Therapy (ART) Suggests Association with Chronic Inflammation

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

34378948

DOI Digital object identifier for electronic documents.

10.1128/Spectrum.00708-21

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552706/pdf/spectrum.00708-21.pdf

Authors

Ishizaka A, Koga M, Mizutani T, Parbie PK, Prawisuda D, Yusa N, Sedohara A, Kikuchi T, Ikeuchi K, Adachi E, Koibuchi T, Furukawa Y, Tojo A, Imoto S, Suzuki Y, Tsutsumi T, Kiyono H, Matano T, Yotsuyanagi H

Journal

Microbiology spectrum

Year

2021

Keywords:

HIV, dysbiosis, human immunodeficiency virus, inflammation, microbiome, microbiota

Chronic inflammation is a hallmark of human immunodeficiency virus (HIV) infection and a risk factor for the development and progression of age-related comorbidities. Although HIV-associated gut dysbiosis has been suggested to be involved in sustained chronic inflammation, there remains a limited understanding of the association between gut dysbiosis and chronic inflammation during HIV infection. Here, we investigated compositional changes in the gut microbiome and its role in chronic inflammation in patients infected with HIV. We observed that the gut microbiomes of patients with low CD4 counts had reduced alpha diversity compared to those in uninfected controls. Following CD4 recovery, alpha diversity was restored, but intergroup dissimilarity of bacterial composition remained unchanged between patients and uninfected controls. Patients with HIV had higher abundance of the classes Negativicutes, Bacilli, and Coriobacteriia, as well as depletion of the class Clostridia. These relative abundances positively correlated with inflammatory cytokines and negatively correlated with anti-inflammatory cytokines. We found that gut dysbiosis accompanying HIV infection was characterized by a depletion of obligate anaerobic Clostridia and enrichment of facultative anaerobic bacteria, reflecting increased intestinal oxygen levels and intestinal permeability. Furthermore, it is likely that HIV-associated dysbiosis shifts the immunological balance toward inflammatory Th1 responses and encourages proinflammatory cytokine production. Our results suggest that gut dysbiosis contributes to sustaining chronic inflammation in patients with HIV infection despite effective antiretroviral therapy and that correcting gut dysbiosis will be effective in improving long-term outcomes in patients. IMPORTANCE Chronic inflammation is a hallmark of HIV infection and is associated with the development and progression of age-related comorbidities. Although the gastrointestinal tract is a major site of HIV replication and CD4+ T-cell depletion, the role of HIV-associated imbalance of gut microbiome in chronic inflammation is unclear. Here, we aimed to understand the causal relationship between abnormalities in the gut microbiome and chronic inflammation in patients with HIV. Our results suggest HIV-associated gut dysbiosis presents a more aerobic environment than that of healthy individuals, despite prolonged viral suppression. This dysbiosis likely results from a sustained increase in intestinal permeability, which supports sustained bacterial translocation in HIV patients, despite effective therapy. Additionally, we observed that several bacterial taxa enriched in HIV patients were associated with increased expression of inflammatory cytokines. Collectively, these results suggest that gut dysbiosis plays an important role in chronic inflammation in HIV patients.

Experiment 1

Edit History Delete

Mark reviewed

Your review change was submittedDuplicate this Experiment Add a new Signature

Needs review

Curated date: 2022/01/09

Curator:

Revision editor(s):

Subjects

Location of subjects: Japan

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: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

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

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with HIV infection

Group 0 sample size Number of subjects in the control (unexposed) group: 61

Group 1 sample size Number of subjects in the case (exposed) group: 71

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)?: No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 3.0

Matched on Factors on which subjects have been matched on in a case-control study: age, body mass index, sex

Alpha Diversity

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

Richness Number of species: unchanged

Signature 1

Edit History Delete

Flag for review

Your review change was submitted

Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2022/01/09

Curator: Joyessa

Revision editor(s): Joyessa, Claregrieve1, WikiWorks

Source: Figure 2, Figure 3

Description: Differential microbial abundance between healthy controls and HIV-infected patients with CD4 counts > 500 cells/uL

Abundance in Group 1: increased abundance in

NCBI	Quality Control	Links
Actinomycetota
Oribacterium
Solobacterium
Lactobacillus
Lactobacillaceae
Merdimmobilis
Olsenella
Enterorhabdus
Mogibacterium
Aeromonadales
Parolsenella
Succinivibrionaceae
Succinivibrio
Megasphaera
Actinomycetaceae
Actinomycetales
Senegalimassilia
Slackia
Atopobiaceae
Holdemanella
Collinsella
Coriobacteriaceae
Erysipelotrichaceae
Acidaminococcaceae
Acidaminococcales
Catenibacterium
Eggerthellaceae
Prevotella
Erysipelotrichales
Prevotellaceae
Megamonas
Selenomonadaceae
Dialister
Bacilli
Coriobacteriia
Coriobacteriales
Veillonellaceae
Veillonellales
Selenomonadales
Negativicutes

Revision editor(s): Joyessa, Claregrieve1, WikiWorks

Signature 2

Edit History Delete

Flag for review

Your review change was submitted

Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2022/01/09

Curator: Joyessa

Revision editor(s): Joyessa, Claregrieve1, WikiWorks

Source: Figure 3

Description: Differential microbial abundance between healthy controls and HIV-infected patients with CD4 counts > 500 cells/uL

Abundance in Group 1: decreased abundance in

NCBI	Quality Control	Links
Clostridia
Bacteroides
Bacteroidaceae
Enterobacteriaceae
Anaerostipes
Monoglobus
Alistipes
Fusicatenibacter
Rikenellaceae
Enterobacter
Carnobacteriaceae
Granulicatella
Pasteurellaceae
Haemophilus
Oscillospiraceae

Revision editor(s): Joyessa, Claregrieve1, WikiWorks