Association of gut microbiota with the pathogenesis of SARS-CoV-2 Infection in people living with HIV

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Reviewed Marked as Reviewed by Svetlana up on 2024-6-20
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Aya Ishizaka, Eisuke Adachi, Hiroshi Yotsuyanagi, Kiyoko Iwatsuki-Horimoto, Michiko Koga, Seiya Yamayoshi, Taketoshi Mizutani, Yoshihiro Kawaoka, Yutaka Suzuki
Journal
BMC microbiology
Year
2024
Pages:
First page:
Keywords:
SARS-CoV-2, COVID-19, HIV, Microbiota, Post-acute COVID-19 syndrome
Background

People living with HIV (PLWH) with chronic inflammation may have an increasing risk for coronavirus disease 2019 (COVID-19) severity; however, the impact of their gut microbiota on COVID-19 is not fully elucidated. Here, we analyzed the temporal changes in the gut microbiota composition of hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected PLWH (PLWH-CoV) and their correlation with COVID-19 severity.

Result The 16S rRNA analysis results using stool samples (along the timeline from disease onset) from 12 hospitalized PLWH-CoV, whose median CD4 + T cell count was 671 cells/µl, were compared to those of 19 healthy people and 25 PLWH. Bacterial diversity in PLWH-CoV is not significantly different from that of healthy people and SARS-CoV-2 non-infected PLWH, but a significant difference in the microbiota diversity was observed in the classification according to the disease severity. Immediately after the disease onset, remarkable changes were observed in the gut microbiota of PLWH-CoV, and the changing with a decrease in some short-chain fatty acid-producing bacteria and an increase in colitis-related pathobiont. In the second week after disease onset, relative amounts of specific bacteria distinguished between disease severity. One month after the disease onset, dysbiosis of the gut microbiota persisted, and the number of Enterobacteriaceae, mainly Escherichia-Shigella, which is potentially pathogenic, increased and were enriched in patients who developed post-acute sequelae of COVID-19 (PASC).

Conclusion The changes in the gut microbiota associated with SARS-CoV-2 infection observed in PLWH in this study indicated a persistent decrease in SCFA-producing bacteria and an intestinal environment with an increase in opportunistic pathogens associated with enteritis. This report demonstrates that the intestinal environment in PLWH tends to show delayed improvement even after COVID-19 recovery, and highlights the importance of the dysbiosis associated with SARS-CoV-2 infection as a potential factor in the COVID-19 severity and the PASC in PLWH.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/03/20

Curator: Ardeybisi

Revision editor(s): Svetlana up, Scholastica, Adenike Oladimeji-Kasumu, Ardeybisi

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
SARS coronavirus HCoV-SARS,Human coronavirus (strain SARS),SARS virus,Severe acute respiratory syndrome coronavirus,SARS coronavirus,sARS coronavirus
Group 0 name Corresponds to the control (unexposed) group for case-control studies
SARS-CoV-2-uninfected PLWH (< 8 days)
Group 1 name Corresponds to the case (exposed) group for case-control studies
SARS-CoV-2-infected PLWH (< 8 days)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected PLWH (People living with HIV) within 7 days of COVID-19 onset (< 8 days)
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
10
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None

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
MaAsLin2
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
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
body mass index

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/03/21

Curator: Ardeybisi

Revision editor(s): Ardeybisi, Adenike Oladimeji-Kasumu

Source: Figure 2C

Description: Changes in gut microbiota in SARS-CoV-2 infected PLWH were analyzed using linear discriminant analysis (LDA) effect size in comparison with the SARS-CoV-2 uninfected PLWH within 7 days of COVID-19 onset.

Abundance in Group 1: increased abundance in SARS-CoV-2-infected PLWH (< 8 days)

NCBI Quality ControlLinks
Eggerthella
Ruminococcus sp.
Alistipes
Bacteroides
Bacteroidaceae

Revision editor(s): Ardeybisi, Adenike Oladimeji-Kasumu

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/03/21

Curator: Ardeybisi

Revision editor(s): Ardeybisi, Adenike Oladimeji-Kasumu

Source: Figure 2C

Description: Changes in gut microbiota in SARS-CoV-2 infected PLWH were analyzed using linear discriminant analysis (LDA) effect size in comparison with the SARS-CoV-2 uninfected PLWH within 7 days of COVID-19 onset.

Abundance in Group 1: decreased abundance in SARS-CoV-2-infected PLWH (< 8 days)

NCBI Quality ControlLinks
Agathobacter
Butyricicoccus
Dorea
Eubacterium ruminantium
Fusicatenibacter
Megasphaera
Mitsuokella
Peptostreptococcaceae bacterium
Veillonellaceae

Revision editor(s): Ardeybisi, Adenike Oladimeji-Kasumu

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/03/20

Curator: Ardeybisi

Revision editor(s): Ardeybisi, Adenike Oladimeji-Kasumu, Scholastica

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
SARS-CoV-2-uninfected PLWH (8–14 days)
Group 1 name Corresponds to the case (exposed) group for case-control studies
SARS-CoV-2-infected PLWH (8–14 days)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected PLWH (People living with HIV) 8 − 14 days after COVID-19 onset
Group 0 sample size Number of subjects in the control (unexposed) group
9
Group 1 sample size Number of subjects in the case (exposed) group
9

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/04/08

Curator: Adenike Oladimeji-Kasumu

Revision editor(s): Adenike Oladimeji-Kasumu

Source: Figure 2D

Description: Changes in gut microbiota in SARS-CoV-2 infected PLWH were analyzed using linear discriminant analysis (LDA) effect size in comparison with the SARS-CoV-2 uninfected PLWH 8−14 days after COVID-19 onset.

Abundance in Group 1: increased abundance in SARS-CoV-2-infected PLWH (8–14 days)

NCBI Quality ControlLinks
Lachnoanaerobaculum
Peptoniphilus
Mogibacterium
Dielma
Eggerthellaceae
Corynebacterium
Bacteroides
Bacteroidaceae

Revision editor(s): Adenike Oladimeji-Kasumu

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/04/08

Curator: Adenike Oladimeji-Kasumu

Revision editor(s): Adenike Oladimeji-Kasumu

Source: Figure 2D

Description: Changes in gut microbiota in SARS-CoV-2 infected PLWH were analyzed using linear discriminant analysis (LDA) effect size in comparison with the SARS-CoV-2 uninfected PLWH 8−14 days after COVID-19 onset.

Abundance in Group 1: decreased abundance in SARS-CoV-2-infected PLWH (8–14 days)

NCBI Quality ControlLinks
Megasphaera
Acidaminococcus
Veillonellaceae
Selenomonadales
Lachnoclostridium
Agathobacter
Anaerostipes

Revision editor(s): Adenike Oladimeji-Kasumu

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/03/21

Curator: Ardeybisi

Revision editor(s): Ardeybisi, Adenike Oladimeji-Kasumu, Scholastica

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
SARS-CoV-2-uninfected PLWH (>1 M)
Group 1 name Corresponds to the case (exposed) group for case-control studies
SARS-CoV-2-infected PLWH (>1 M)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected PLWH (People living with HIV) over 1 month after COVID-19 onset
Group 0 sample size Number of subjects in the control (unexposed) group
7
Group 1 sample size Number of subjects in the case (exposed) group
7

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/04/08

Curator: Adenike Oladimeji-Kasumu

Revision editor(s): Adenike Oladimeji-Kasumu

Source: Figure 2E

Description: Changes in gut microbiota in SARS-CoV-2 infected PLWH were analyzed using linear discriminant analysis (LDA) effect size in comparison with the SARS-CoV-2 uninfected PLWH over 1 month after COVID-19 onset.

Abundance in Group 1: increased abundance in SARS-CoV-2-infected PLWH (>1 M)

NCBI Quality ControlLinks
Candidatus Saccharimonas
Dickeya
Enterobacteriaceae
Enterobacteriaceae bacterium
Gammaproteobacteria
Rhizobiaceae
Enterobacterales
Escherichia/Shigella sp.

Revision editor(s): Adenike Oladimeji-Kasumu

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/04/08

Curator: Adenike Oladimeji-Kasumu

Revision editor(s): Adenike Oladimeji-Kasumu, Scholastica

Source: Figure 2E

Description: Changes in gut microbiota in SARS-CoV-2 infected PLWH were analyzed using linear discriminant analysis (LDA) effect size in comparison with the SARS-CoV-2 uninfected PLWH over 1 month after COVID-19 onset.

Abundance in Group 1: decreased abundance in SARS-CoV-2-infected PLWH (>1 M)

NCBI Quality ControlLinks
Agathobacter
Clostridia
Fusicatenibacter
Roseburia
Ruminococcaceae UCG_002Ruminococcaceae UCG_002
Eubacteriales

Revision editor(s): Adenike Oladimeji-Kasumu, Scholastica

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/06/20

Curator: Scholastica

Revision editor(s): Scholastica

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Illness severity status Illness severity status,illness severity status
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mildly ill SARS-CoV-2-infected PLWH (8–14 days)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Moderately/severely ill SARS-CoV-2-infected PLWH (8–14 days)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Moderately (n = 4) and severely (n = 1) ill hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected PLWH (People living with HIV) within 7 days of COVID-19 onset (8–14 days)
Group 0 sample size Number of subjects in the control (unexposed) group
6
Group 1 sample size Number of subjects in the case (exposed) group
5

Lab analysis

Statistical Analysis

Statistical test
LEfSe

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/06/20

Curator: Scholastica

Revision editor(s): Scholastica

Source: Figure 3F

Description: Changes in the gut microbiota in PLWH-CoV (8-14 days) analyzed by linear discriminant analysis (LDA) effect size, compared by disease severity (mild, n = 6 vs. moderate/severe, n = 5)

Abundance in Group 1: increased abundance in Moderately/severely ill SARS-CoV-2-infected PLWH (8–14 days)

NCBI Quality ControlLinks
Anaerotruncus
Ruminococcaceae UCG_009Ruminococcaceae UCG_009

Revision editor(s): Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-20

Curated date: 2024/06/20

Curator: Scholastica

Revision editor(s): Scholastica

Source: Figure 3F

Description: Changes in the gut microbiota in PLWH-CoV (8-14 days) analyzed by linear discriminant analysis (LDA) effect size, compared by disease severity (mild, n = 6 vs. moderate/severe, n = 5)

Abundance in Group 1: decreased abundance in Moderately/severely ill SARS-CoV-2-infected PLWH (8–14 days)

NCBI Quality ControlLinks
Prevotella9Prevotella9
Alloprevotella
Collinsella
Coriobacteriaceae
Pasteurellaceae
Pasteurellales
Blautia
Dorea
Clostridia
Eubacteriales
unclassified Pasteurellaceae

Revision editor(s): Scholastica