HIV Infection is associated with compositional and functional shifts in the rectal mucosal microbiota

From BugSigDB
Needs review
study design
cross-sectional observational, not case-control
Citation
PMID
URI
Authors
McHardy IH, Li X, Tong M, Ruegger P, Jacobs J, Borneman J, Anton P, Braun J
Journal
Microbiome
Year
2013
BACKGROUND: Regardless of infection route, the intestine is the primary site for HIV-1 infection establishment and results in significant mucosal CD4+ T lymphocyte depletion, induces an inflammatory state that propagates viral dissemination, facilitates microbial translocation, and fosters establishment of one of the largest HIV reservoirs. Here we test the prediction that HIV infection modifies the composition and function of the mucosal commensal microbiota. RESULTS: Rectal mucosal microbiota were collected from human subjects using a sponge-based sampling methodology. Samples were collected from 20 HIV-positive men not receiving combination anti-retroviral therapy (cART), 20 HIV-positive men on cART and 20 healthy, HIV-negative men. Microbial composition of samples was analyzed using barcoded 16S Illumina deep sequencing (85,900 reads per sample after processing). Microbial metagenomic information for the samples was imputed using the bioinformatic tools PICRUST and HUMAnN. Microbial composition and imputed function in HIV-positive individuals not receiving cART was significantly different from HIV-negative individuals. Genera including Roseburia, Coprococcus, Ruminococcus, Eubacterium, Alistipes and Lachnospira were depleted in HIV-infected subjects not receiving cART, while Fusobacteria, Anaerococcus, Peptostreptococcus and Porphyromonas were significantly enriched. HIV-positive subjects receiving cART exhibited similar depletion and enrichment for these genera, but were of intermediate magnitude and did not achieve statistical significance. Imputed metagenomic functions, including amino acid metabolism, vitamin biosynthesis, and siderophore biosynthesis differed significantly between healthy controls and HIV-infected subjects not receiving cART. CONCLUSIONS: HIV infection was associated with rectal mucosal changes in microbiota composition and imputed function that cART failed to completely reverse. HIV infection was associated with depletion of some commensal species and enrichment of a few opportunistic pathogens. Many imputed metagenomic functions differed between samples from HIV-negative and HIV-positive subjects not receiving cART, possibly reflecting mucosal metabolic changes associated with HIV infection. Such functional pathways may represent novel interventional targets for HIV therapy if normalizing the microbial composition or functional activity of the microbiota proves therapeutically useful.

Experiment 1


Needs review

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743

Subjects

Location of subjects Country from which study subjects were recruited
United States of America
Host species Species from which microbiome was sampled (if applicable)
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV infection [X]Human immunodeficiency virus disease,[X]Human immunodeficiency virus disease (disorder),[X]Unspecified human immunodeficiency virus [HIV] disease,[X]Unspecified human immunodeficiency virus [HIV] disease (disorder),HIV - Human immunodeficiency virus infection,HIV INFECT,HIV Infection,HIV infection,HIV Infections,HIV infectious disease,HTLV III INFECT,HTLV III Infections,HTLV III LAV INFECT,HTLV III LAV Infections,HTLV WIII INFECTIONS,HTLV WIII LAV INFECTIONS,HTLV-III Infection,HTLV-III Infections,HTLV-III-LAV Infection,HTLV-III-LAV Infections,HUMAN IMMUNO VIRUS DIS,human immunodeficiency virus,Human immunodeficiency virus [HIV] disease,HUMAN IMMUNOdeficiency VIRUS [HIV] INFECTION,Human immunodeficiency virus caused disease or disorder,Human immunodeficiency virus disease,Human immunodeficiency virus disease (disorder),Human immunodeficiency virus disease or disorder,Human immunodeficiency virus infection,Human immunodeficiency virus infection (disorder),Human immunodeficiency virus infection, NOS,Human immunodeficiency virus infectious disease,human immunodeficiency virus infectious disease,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,LYMPHOTROPIC VIRUS TYPE III INFECTIONS HUMAN T,T LYMPHOTROPIC VIRUS TYPE III INFECT HUMAN,T Lymphotropic Virus Type III Infections, Human,T-Lymphotropic Virus Type III Infections, Human,Unspecified human immunodeficiency virus [HIV] disease (disorder)
Group 0 name Corresponds to the control (unexposed) group for case-control studies
HC
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV infected cART negative
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
HIV infected patients not on combined anti-retroviral therapy
Group 0 sample size Number of subjects in the control (unexposed) group
20
Group 1 sample size Number of subjects in the case (exposed) group
40

Lab analysis

Sequencing type Experimental technique used for quantifying microbial abundance
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

Statistical test Statistical test or computational tool used for differential abundance testing
Kruskall-Wallis
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.15
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes


Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Needs review

Curated date: 2020-03-18

Curator: Fatima Zohra

Revision editor(s): WikiWorks743

Source: Figure 3

Description: Phylogenetic differences in HIV subjects not on combination anti-retroviral therpay

Abundance in Group 1: increased abundance in HIV infected cART negative

NCBI Links
Fusobacteria
Fusobacteriia
Peptostreptococcaceae
Fusobacteriaceae
Anaerococcus
Peptostreptococcus
Porphyromonas
Fusobacterium

Revision editor(s): WikiWorks743

Signature 2

Needs review

Curated date: 2020-03-18

Curator: Fatima Zohra

Revision editor(s): WikiWorks743

Source: Figure 3

Description: Phylogenetic differences in HIV subjects not on combination anti-retroviral therpay

Abundance in Group 1: decreased abundance in HIV infected cART negative

NCBI Links
Firmicutes
Clostridia
Eubacteriales
Lachnospiraceae
Oscillospiraceae
Rikenellaceae
Lachnospira
Coprococcus
Roseburia
Eubacterium
Ruminococcus
Alistipes

Revision editor(s): WikiWorks743