Long-term benefit of DAAs on gut dysbiosis and microbial translocation in HCV-infected patients with and without HIV coinfection

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Reviewed Marked as Reviewed by Svetlana up on 2024-9-13
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Chuaypen N, Jinato T, Avihingsanon A, Nookaew I, Tanaka Y, Tangkijvanich P
Journal
Scientific reports
Year
2023
Long-term effect of Direct-acting antivirals (DAAs) on gut microbiota, short-chain fatty acids (SCFAs) and microbial translocation in patients with hepatitis C virus (HCV) infection who achieve sustained virological response (SVR) were limited. A longitudinal study of 50 patients with HCV monoinfection and 19 patients with HCV/HIV coinfection received DAAs were conducted. Fecal specimens collected at baseline and at week 72 after treatment completion (FUw72) were analyzed for 16S rRNA sequencing and the butyryl-CoA:acetateCoA transferase (BCoAT) gene expression using real-time PCR. Plasma lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP) were quantified by ELISA assays. SVR rates in mono- and coinfected patients were comparable (94% vs. 100%). The improvement of gut dysbiosis and microbial translocation was found in responders but was not in non-responders. Among responders, significant restoration of alpha-diversity, BCoAT and LBP were observed in HCV patients with low-grade fibrosis (F0-F1), while HCV/HIV patients exhibited partial improvement at FUw72. I-FABP did not decline significantly in responders. Treatment induced microbiota changes with increasing abundance of SCFAs-producing bacteria, including Blautia, Fusicatenibacter, Subdoligranulum and Bifidobacterium. In conclusion, long-term effect of DAAs impacted the restoration of gut dysbiosis and microbial translocation. However, early initiation of DAAs required for an alteration of gut microbiota, enhanced SCFAs-producing bacteria, and could reduce HCV-related complications.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/02

Curator: Scholastica

Revision editor(s): Scholastica, Idiaru angela

Subjects

Location of subjects
Thailand
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
Response to antiviral drug Response to antiviral drug,response to antiviral drug
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
Patients at baseline - SVR
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients at baseline with HCV monoinfection and HCV/HIV coinfection who achieved sustained virological response (SVR)
Group 0 sample size Number of subjects in the control (unexposed) group
20
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Patients were asked to stop antibiotics within 2 weeks before acceptance and during the study period.

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
Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances

Alpha Diversity

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

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/02

Curator: Scholastica

Revision editor(s): Scholastica, Idiaru angela

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Baseline - SVR
Group 1 name Corresponds to the case (exposed) group for case-control studies
Follow-up at week 72 (FUw72) -SVR
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients at week 72 after treatment completion who achieved sustained virological response (SVR)
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
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

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/05

Curator: Scholastica

Revision editor(s): Scholastica

Source: Table 2

Description: Significant taxa (≥ 1%) at genus levels in patients with SVR

Abundance in Group 1: increased abundance in Follow-up at week 72 (FUw72) -SVR

NCBI Quality ControlLinks
Blautia
Bifidobacterium
Subdoligranulum
Dorea
Megamonas
Collinsella
Ruminococcus torques groupRuminococcus torques group
Fusicatenibacter
Eubacterium hallii groupEubacterium hallii group
Coprococcus
Anaerostipes
Megasphaera
Holdemanella
Streptococcus

Revision editor(s): Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/05

Curator: Scholastica

Revision editor(s): Scholastica

Source: Table 2

Description: Significant taxa (≥ 1%) at genus levels in patients with SVR

Abundance in Group 1: decreased abundance in Follow-up at week 72 (FUw72) -SVR

NCBI Quality ControlLinks
Bacteroides
Lachnoclostridium
Sutterella
Lachnospira
Eubacterium eligens groupEubacterium eligens group

Revision editor(s): Scholastica

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/02

Curator: Scholastica

Revision editor(s): Scholastica, Idiaru angela

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls
Group 0 sample size Number of subjects in the control (unexposed) group
20

Lab analysis

Statistical test
Not specified
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
Not specified
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Not specified

Alpha Diversity

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

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/02

Curator: Scholastica

Revision editor(s): Scholastica, Idiaru angela

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Patients with mild fibrosis at baseline (F0–F1)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients with mild fibrosis at FUw72 (F0–F1)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with mild fibrosis (F0–F1) at week 72 after treatment completion
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified

Lab analysis

Alpha Diversity

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

Experiment 5


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/02

Curator: Scholastica

Revision editor(s): Scholastica, Idiaru angela

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Patients with significant fibrosis to cirrhosis at baseline (F2–F4)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients with significant fibrosis to cirrhosis at FUw72 (F2–F4)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with significant fibrosis to cirrhosis (F2–F4) at week 72 after treatment completion (FUw72)

Lab analysis

Alpha Diversity

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

Experiment 6


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/02

Curator: Scholastica

Revision editor(s): Scholastica, Idiaru angela

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Patients with HCV monoinfection & (F2-F4) fibrosis at baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients with HCV monoinfection & (F2-F4) fibrosis at FUw72
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with HCV monoinfection and significant fibrosis to cirrhosis (F2-F4) at week 72 after treatment completion (FUw72).

Lab analysis

Alpha Diversity

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

Experiment 7


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/02

Curator: Scholastica

Revision editor(s): Scholastica, Idiaru angela

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Patients with HCV/HIV coinfection at baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients with HCV/HIV coinfection at FUw72
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with HCV/HIV coinfection at week 72 after treatment completion (FUw72)
Group 0 sample size Number of subjects in the control (unexposed) group
24
Group 1 sample size Number of subjects in the case (exposed) group
19

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
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

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/04

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Source: Table S4

Description: Differential abundance at genus levels in baseline and follow-up week-72 (FUw72) of patients with HCV/HIV coinfection

Abundance in Group 1: increased abundance in Patients with HCV/HIV coinfection at FUw72

NCBI Quality ControlLinks
Blautia
Agathobacter
Bifidobacterium
Megamonas
Collinsella
Ruminococcus torques groupRuminococcus torques group
Dorea
Eubacterium hallii groupEubacterium hallii group
Coprococcus

Revision editor(s): Idiaru angela

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/04

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Source: Table S3

Description: Differential abundance at genus levels in baseline and follow-up week-72 (FUw72) of patients with HCV/HIV coinfection

Abundance in Group 1: decreased abundance in Patients with HCV/HIV coinfection at FUw72

NCBI Quality ControlLinks
Bacteroides
Prevotella
Lachnospiraceae NK4A136 groupLachnospiraceae NK4A136 group

Revision editor(s): Idiaru angela

Experiment 8


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/02

Curator: Scholastica

Revision editor(s): Scholastica, Idiaru angela

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Patients with HCV monoinfection + mild fibrosis at baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients with HCV monoinfection + mild fibrosis at FUw72
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with HCV monoinfection who had F0–F1 fibrosis stage at week 72 after treatment completion (FUw72)
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified

Lab analysis

Statistical test
Not specified
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
Not specified
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Not specified

Alpha Diversity

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

Experiment 9


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/02

Curator: Scholastica

Revision editor(s): Scholastica, Idiaru angela

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Patients with HCV monoinfection + significant fibrosis at baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients with HCV monoinfection + significant fibrosis at FUw72
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with HCV monoinfection who had F2–F4 fibrosis stage at week 72 after treatment completion (FUw72)

Lab analysis

Alpha Diversity

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

Experiment 10


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/02

Curator: Scholastica

Revision editor(s): Scholastica, Idiaru angela

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Patients with HCV/HIV coinfection + mild fibrosis at baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients with HCV/HIV coinfection + mild fibrosis at FUw72
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with HCV/HIV coinfection who had F0–F1 fibrosis stage at week 72 after treatment completion (FUw72)

Lab analysis

Alpha Diversity

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

Experiment 11


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/03

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
patients with HCV monoinfection at baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
patients with HCV monoinfection at FUw72
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients with HCV monoinfection at week 72 after treatment completion (FUw72)
Group 0 sample size Number of subjects in the control (unexposed) group
62
Group 1 sample size Number of subjects in the case (exposed) group
50

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
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

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/04

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Source: Table S3

Description: Differential abundance at genus levels in baseline and follow-up week-72 (FUw72) of patients with HCV monoinfection

Abundance in Group 1: increased abundance in patients with HCV monoinfection at FUw72

NCBI Quality ControlLinks
Bifidobacterium
Blautia
Collinsella
Dorea
Fusicatenibacter
Subdoligranulum
Ruminococcus torques groupRuminococcus torques group
Eubacterium hallii groupEubacterium hallii group

Revision editor(s): Idiaru angela

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/04

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Source: Table S3

Description: Differential abundance at genus levels in baseline and follow-up week-72 (FUw72) of patients with HCV monoinfection

Abundance in Group 1: decreased abundance in patients with HCV monoinfection at FUw72

NCBI Quality ControlLinks
Bacteroides
Lachnoclostridium

Revision editor(s): Idiaru angela

Experiment 12


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/03

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Differences from previous experiment shown

Subjects

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
patients with HCV monoinfection at baseline
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients with HCV monoinfection at baseline
Group 0 sample size Number of subjects in the control (unexposed) group
20

Lab analysis

Statistical Analysis

Statistical test
T-Test


Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/03

Curator: Idiaru angela

Revision editor(s): Idiaru angela, Scholastica

Source: Table S2

Description: Gut microbiota composition at baseline comparing Healthy controls vs patients with HCV monoinfection

Abundance in Group 1: decreased abundance in patients with HCV monoinfection at baseline

NCBI Quality ControlLinks
Clostridium
Collinsella
Lachnospira
Parabacteroides
Romboutsia
Subdoligranulum
UCG-002UCG-002
CAG-352CAG-352
Christensenellaceae R7 groupChristensenellaceae R7 group
Lachnospiraceae UCG-004Lachnospiraceae UCG-004
Lachnospiraceae ND3007 groupLachnospiraceae ND3007 group
Lachnospiraceae bacterium NK4A136
uncultured Erysipelotrichaceae bacterium

Revision editor(s): Idiaru angela, Scholastica

Experiment 13


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/04

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Differences from previous experiment shown

Subjects

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
patients with HCV/HIV coinfection at baseline
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with HIV/HCV coinfection at baseline
Group 1 sample size Number of subjects in the case (exposed) group
19

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/04

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Source: Table S2

Description: Gut microbiota composition at baseline comparing Healthy controls vs patients with HCV/HIV coinfection

Abundance in Group 1: increased abundance in patients with HCV/HIV coinfection at baseline

NCBI Quality ControlLinks
Alloprevotella
Catenibacterium

Revision editor(s): Idiaru angela

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/04

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Source: Table S2

Description: Gut microbiota composition at baseline comparing Healthy controls vs patients with HCV/HIV coinfection

Abundance in Group 1: decreased abundance in patients with HCV/HIV coinfection at baseline

NCBI Quality ControlLinks
Blautia
Collinsella
Alistipes
Subdoligranulum
Fusicatenibacter
Lachnospira
Coprococcus
Lachnospiraceae UCG-004Lachnospiraceae UCG-004
Clostridium
Erysipelotrichaceae UCG-003Erysipelotrichaceae UCG-003
Lachnospiraceae ND3007 groupLachnospiraceae ND3007 group

Revision editor(s): Idiaru angela

Experiment 14


Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/04

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
patients with HCV monoinfection at baseline
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients with HCV/HIV coinfection at baseline
Group 0 sample size Number of subjects in the control (unexposed) group
50

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/04

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Source: Table S2

Description: Gut microbiota composition at baseline comparing patients with HCV monoinfection vs patients with HCV/HIV coinfection

Abundance in Group 1: increased abundance in patients with HCV/HIV coinfection at baseline

NCBI Quality ControlLinks
Alloprevotella
Succinivibrio

Revision editor(s): Idiaru angela

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-9-13

Curated date: 2024/04/04

Curator: Idiaru angela

Revision editor(s): Idiaru angela

Source: Table S2

Description: Gut microbiota composition at baseline comparing patients with HCV monoinfection vs patients with HCV/HIV coinfection

Abundance in Group 1: decreased abundance in patients with HCV/HIV coinfection at baseline

NCBI Quality ControlLinks
Blautia
Bifidobacterium
[Ruminococcus] torques group[Ruminococcus] torques group
Fusicatenibacter

Revision editor(s): Idiaru angela