Altered gut microbiota correlate with different immune responses to HAART in HIV-infected individuals

From BugSigDB
Reviewed Marked as Reviewed by Peace Sandy on 2024-10-22
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Xie Y, Sun J, Wei L, Jiang H, Hu C, Yang J, Huang Y, Ruan B, Zhu B
Journal
BMC microbiology
Year
2021
Keywords:
Gut microbiota, HAART, HIV-1, Immune activation, Immunological non-responders, Immunological responders
BACKGROUND: Although gut microbiota dysbiosis has been reported in HIV infected individuals recently, the relationship between the gut microbiota and immune activation in patients with different immune responses to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (healthy controls) and 58 HIV-infected individuals, including 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and < 200 CD4+ T-cell counts/μl after 2 years of HIV-1 viral suppression respectively) without comorbidities. RESULTS: Metagenome sequencing revealed that HIV-infected immunological responders and immunological non-responders could not recover completely from the gut microbiota dysbiosis. At a 97% similarity level, the relative abundances of Fusobacterium, Ruminococcus gnavus and Megamonas were greater, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacterium rectale and Roseburia were more depleted in the IR and INR groups than those in the healthy controls. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8 + CD57+ T-cell counts. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundances of genera Ruminococcus and Fusobacterium but were negatively correlated with the genus Faecalibacterium. The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than those in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of CD8 + CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8 + CD57+ T-cell counts. CONCLUSIONS: Gut microbiota dysbiosis may be one of the factors contributing to different immune responses and treatment outcomes to HAART.

Experiment 1


Reviewed Marked as Reviewed by Peace Sandy on 2024-10-22

Curated date: 2024/10/03

Curator: Patience Onah

Revision editor(s): Patience Onah, Peace Sandy

Subjects

Location of subjects
China
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
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),hIV infection
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy HIV negative individual
Group 1 name Corresponds to the case (exposed) group for case-control studies
Immunological Responder (IR) HIV infected individual
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Immunological Responder HIV infected individual(IR), were defined as patients whose CD4+ T-cell counts/μl equal or is more than 500 or less than 200 after 2 years of receiving complete viral suppression therapy respectively. All HIV-positive subjects were on two nucleoside reverse transcriptase inhibitors (NRTIs) + nonnucleoside reverse transcriptase inhibitors (NNRTIs) or the protease inhibitor-based therapy: Zidovudine/Tenofovir Disoproxil Fumarate (AZT/TDF) + Lamivudine (3TC) + Efavirenz (EFV) or Lopinavir/ritonavir (LPV/r).
Group 0 sample size Number of subjects in the control (unexposed) group
36
Group 1 sample size Number of subjects in the case (exposed) group
28
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
6 months Other exclusion criteria include: Candidates having age over 60 years old; having opportunistic infection; having hepatitis B or C infection; having used rectally administered medications within 48 h before selection; BMI > 30; having a history of inflammatory bowel disease (IBD); having active inflammation affecting the gastro intestines.

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)?
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, body mass index

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-22

Curated date: 2024/10/04

Curator: Patience Onah

Revision editor(s): Patience Onah

Source: Additional file 4, figure S4b

Description: Taxonomic differences of fecal microbiota between the immunological responders (IR), and healthy controls (Control) group.

Abundance in Group 1: increased abundance in Immunological Responder (IR) HIV infected individual

NCBI Quality ControlLinks
Abiotrophia
Enterobacter
Escherichia/Shigella sp.
Fusobacterium
Lachnoclostridium
Lachnospiraceae
Megasphaera
Rhodococcus
Streptococcus
Veillonella
Mediterraneibacter gnavus
unclassified Lachnospiraceae

Revision editor(s): Patience Onah

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-22

Curated date: 2024/10/06

Curator: Patience Onah

Revision editor(s): Patience Onah

Source: Additional file 4, figure S4b

Description: Taxonomic differences of fecal microbiota between the immunological non-responders (INR) and healthy controls (Control) group.

Abundance in Group 1: decreased abundance in Immunological Responder (IR) HIV infected individual

NCBI Quality ControlLinks
Alistipes
Anaerobutyricum hallii
Anaerostipes
Bacteroides
Barnesiella
Bifidobacterium
Coprococcus sp.
Eubacterium coprostanoligenes
Eubacterium ruminantium
Eubacterium ventriosum
Faecalibacterium
Fusicatenibacter
Lachnospira eligens
Lachnospiraceae bacterium NK4A136
Oscillospira
Paraprevotella
Parasutterella
Roseburia
Ruminococcaceae bacterium UCG-005
Ruminococcus sp.
Subdoligranulum
Victivallis
Agathobacter rectalis

Revision editor(s): Patience Onah

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2024-10-22

Curated date: 2024/10/03

Curator: Patience Onah

Revision editor(s): Patience Onah, Peace Sandy

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
immunological non-responders (INR) HIV infected individual
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
immunological non-responders (INR), and INR were defined as patients whose CD4+ T-cell counts/μl equal or is more than 500 or less than 200 after 2 years of receiving complete viral suppression therapy respectively. All HIV-positive subjects were on two nucleoside reverse transcriptase inhibitors (NRTIs) + nonnucleoside reverse transcriptase inhibitors (NNRTIs) or the protease inhibitor-based therapy: Zidovudine/Tenofovir Disoproxil Fumarate (AZT/TDF) + Lamivudine (3TC) + Efavirenz (EFV) or Lopinavir/ritonavir (LPV/r).
Group 1 sample size Number of subjects in the case (exposed) group
30
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
6 months. Other exclusion criteria include: Candidates having age over 60 years old; having opportunistic infection; having hepatitis B or C infection; having used rectally administered medications within 48 h before selection; BMI > 30; having a history of inflammatory bowel disease (IBD); having active inflammation affecting the gastro intestines.

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-22

Curated date: 2024/10/10

Curator: Patience Onah

Revision editor(s): Patience Onah

Source: Additional file 4, figure S4 d

Description: Taxonomic differences of fecal microbiota between the, immunological non-responders (INR) and healthy controls (Control) group.

Abundance in Group 1: increased abundance in immunological non-responders (INR) HIV infected individual

NCBI Quality ControlLinks
Fusobacterium
Megasphaera
Subdoligranulum
Parasutterella
Alloprevotella
Ruminococcaceae bacterium UCG-005
Mediterraneibacter gnavus

Revision editor(s): Patience Onah

Signature 6

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-22

Curated date: 2024/10/11

Curator: Patience Onah

Revision editor(s): Patience Onah

Source: Additional file 4, figure S4 d

Description: Taxonomic differences of fecal microbiota between the immunological non-responders (INR) and healthy controls (Control) group.

Abundance in Group 1: decreased abundance in immunological non-responders (INR) HIV infected individual

NCBI Quality ControlLinks
Agathobacter rectalis
Alistipes
Anaerobutyricum hallii
Anaerostipes
Barnesiella
Bifidobacterium
Blautia
Christensenellaceae bacterium
Coprococcus catus
Dorea
Erysipelotrichaceae
Eubacterium coprostanoligenes
Eubacterium ruminantium
Eubacterium ventriosum
Faecalibacterium
Fusicatenibacter
Haemophilus
Lachnospiraceae bacterium 10-1
Lachnospiraceae bacterium NK4A136
Paraprevotella
Prevotella bivia
Roseburia
Ruminococcaceae bacterium UCG-005
Ruminococcus albus

Revision editor(s): Patience Onah

Experiment 3


Reviewed Marked as Reviewed by Peace Sandy on 2024-10-22

Curated date: 2024/10/11

Curator: Patience Onah

Revision editor(s): Patience Onah, Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
immunological non-responders (INR) HIV infected individual
Group 1 name Corresponds to the case (exposed) group for case-control studies
Immunological Responder (IR) HIV infected individual
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Immunological Responder HIV infected individual (IR) was defined as patients whose CD4+ T-cell counts/μl equal or is more than 500 or less than 200 after 2 years of receiving complete viral suppression therapy respectively. All HIV-positive subjects were on two nucleoside reverse transcriptase inhibitors (NRTIs) + nonnucleoside reverse transcriptase inhibitors (NNRTIs) or the protease inhibitor-based therapy: Zidovudine/Tenofovir Disoproxil Fumarate (AZT/TDF) + Lamivudine (3TC) + Efavirenz (EFV) or Lopinavir/ritonavir (LPV/r).
Group 0 sample size Number of subjects in the control (unexposed) group
30
Group 1 sample size Number of subjects in the case (exposed) group
28
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
6 months.

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-22

Curated date: 2024/10/11

Curator: Patience Onah

Revision editor(s): Patience Onah

Source: Additional file 4, figure S4 f

Description: Taxonomic differences of fecal microbiota between the immunological non-responders (INR) and Immunological Responder (IR) HIV infected individual.

Abundance in Group 1: increased abundance in Immunological Responder (IR) HIV infected individual

NCBI Quality ControlLinks
Solobacterium
Dielma
Blautia
Escherichia/Shigella sp.

Revision editor(s): Patience Onah

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-22

Curated date: 2024/10/11

Curator: Patience Onah

Revision editor(s): Patience Onah

Source: Additional file 4, figure S4 f

Description: Taxonomic differences of fecal microbiota between the immunological non-responders (INR) and Immunological Responder (IR) HIV infected

Abundance in Group 1: decreased abundance in Immunological Responder (IR) HIV infected individual

NCBI Quality ControlLinks
Anaerostipes
Eubacterium ruminantium
Alloprevotella
Eubacterium
Ruminiclostridium sp.

Revision editor(s): Patience Onah