A gut microbiome signature for HIV and metabolic dysfunction-associated steatotic liver disease

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Reviewed Marked as Reviewed by Svetlana up on 2024-9-30
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Martínez-Sanz J, Talavera-Rodríguez A, Díaz-Álvarez J, Rosas Cancio-Suárez M, Rodríguez JM, Alba C, Montes ML, Martín-Mateos R, Burgos-Santamaría D, Moreno S, Serrano-Villar S, Sánchez-Conde M
Journal
Frontiers in immunology
Year
2023
Keywords:
HIV, MASLD, NAFLD, gut microbiome, microbiome
INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD), has emerged as an increasingly recognized problem among people living with HIV (PLWH). The gut-liver axis is considered to be strongly implicated in the pathogenesis of MASLD. We aimed to characterize the gut microbiota composition in PLWH and MASLD and compare it with that of two control groups: PLWH without MASLD and individuals with MASLD without HIV infection. METHODS: We collected clinical data and stool samples from participants. Bacterial 16S rRNA genes were amplified, sequenced, and clustered into operational taxonomic unit. Alpha diversity was studied by Shannon and Simpson indexes. To study how different the gut microbiota composition is between the different groups, beta diversity estimation was evaluated by principal coordinate analysis (PCoA) using Bray-Curtis dissimilarity. To further analyze differences in microbiome composition we performed a linear discriminant analysis (LDA) effect size (LEfSe). RESULTS: We included 30 HIV+MASLD+, 30 HIV+MASLD- and 20 HIV-MASLD+ participants. Major butyrate producers, including Faecalibacterium, Ruminococcus, and Lachnospira dominated the microbiota in all three groups. Shannon's and Simpson's diversity metrics were higher among MASLD+ individuals (Kruskal-Wallis p = 0.047). Beta diversity analysis showed distinct clustering in MASLD-, with MASLD+ participants overlapping regardless of HIV status (ADONIS significance <0.001). MASLD was associated with increased homogeneity across individuals, in contrast to that observed in the HIV+NAFDL- group, in which the dispersion was higher (Permanova test, p value <0.001; ANOSIM, p value <0.001). MASLD but not HIV determined a different microbiota structure (HIV+MASLD- vs. HIV+MASLD+, q-value = 0.002; HIV-MASLD+ vs. HIV+MASLD+, q-value = 0.930; and HIV-MASLD+ vs. HIV+MASLD-, q-value < 0.001). The most abundant genera in MASLD- were Prevotella, Bacteroides, Dialister, Acidaminococcos, Alloprevotella, and Catenibacterium. In contrast, the most enriched genera in MASLD+ were Ruminococcus, Streptococcus, Holdemanella, Blautia, and Lactobacillus. CONCLUSIONS: We found a microbiome signature linked to MASLD, which had a greater influence on the overall structure of the gut microbiota than HIV status alone.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-9-30

Curated date: 2024/05/05

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Subjects

Location of subjects
Spain
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
Non-alcoholic fatty liver disease fatty liver disease, nonalcoholic,fatty liver disease, nonalcoholic, susceptibility to, 1,liver disease, alcoholic, susceptibility to, 1,NAFLD - Nonalcoholic Fatty Liver Disease,NAFLD - nonalcoholic fatty liver disease,NAFLD1,non-alcoholic fatty liver,non-alcoholic fatty liver disease,Nonalcoholic Fatty Liver Disease,nonalcoholic fatty liver disease,Non-alcoholic fatty liver disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
HIV- MASLD+
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV+ MASLD+
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants living with HIV (PLWH) and Metabolic dysfunction-associated steatotic liver disease (MASLD).
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
30

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
4

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-9-30

Curated date: 2024/05/05

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure S2

Description: LEfSe analysis graph indicating differentially abundant bacterial genera between the different study groups. Only those genus whose LDA score was greater than 4 have been represented.

Abundance in Group 1: increased abundance in HIV+ MASLD+

NCBI Quality ControlLinks
Lachnospiraceae bacterium NK3A20
Dorea
Lachnospiraceae UCG-008Lachnospiraceae UCG-008
Tyzzerella
Mogibacterium
Solobacterium
Romboutsia
Ruminococcus gauvreauii
Clostridium
Lachnospiraceae bacterium NK4A136
[Ruminococcus] torques
Peptococcus
Methanobrevibacter
Marvinbryantia
Mediterraneibacter gnavus
Holdemanella
Blautia
uncultured bacterium
Lachnoclostridium

Revision editor(s): Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-9-30

Curated date: 2024/05/05

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure S2

Description: LEfSe analysis graph indicating differentially abundant bacterial genera between the different study groups. Only those genus whose LDA score was greater than 4 have been represented.

Abundance in Group 1: decreased abundance in HIV+ MASLD+

NCBI Quality ControlLinks
Ruminiclostridium
Enterococcus
Pantoea
Clostridium sp. CAG:352
Yersinia
Lactobacillus
Ruminococcus
Streptococcus
Agathobacter
Escherichia/Shigella sp.
Anaerobutyricum hallii
Roseburia
Alistipes
Subdoligranulum
Weissella
Anaerostipes

Revision editor(s): Aleru Divine

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-9-30

Curated date: 2024/05/05

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
HIV+ MASLD-
Group 0 sample size Number of subjects in the control (unexposed) group
30

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-9-30

Curated date: 2024/05/05

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure S2

Description: LEfSe analysis graph indicating differentially abundant bacterial genera between the different study groups. Only those genus whose LDA score was greater than 4 have been represented.

Abundance in Group 1: increased abundance in HIV+ MASLD+

NCBI Quality ControlLinks
Lachnospiraceae bacterium NK3A20
Dorea
Lachnospiraceae UCG-008Lachnospiraceae UCG-008
Tyzzerella
Mogibacterium
Solobacterium
Romboutsia
Ruminococcus gauvreauii
Clostridium
Lachnospiraceae bacterium NK4A136
[Ruminococcus] torques
Peptococcus
Methanobrevibacter
Marvinbryantia
Mediterraneibacter gnavus
Holdemanella
Blautia
uncultured bacterium
Lachnoclostridium

Revision editor(s): Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-9-30

Curated date: 2024/05/05

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure S2

Description: LEfSe analysis graph indicating differentially abundant bacterial genera between the different study groups. Only those genus whose LDA score was greater than 4 have been represented.

Abundance in Group 1: decreased abundance in HIV+ MASLD+

NCBI Quality ControlLinks
Acidaminococcus
Alloprevotella
Anaerovibrio
Asteroleplasma
Catenibacterium
Collinsella
Megasphaera
Mitsuokella
Parabacteroides
Paraprevotella
Phascolarctobacterium
Porphyromonas
Prevotella
Prevotella sp.
Prevotella sp. 2-3
Succinivibrio
Sutterella
Rikenellaceae RC9 gut groupRikenellaceae RC9 gut group
Prevotellaceae NK3B31 groupPrevotellaceae NK3B31 group
Prevotellaceae UCG-001Prevotellaceae UCG-001
Dialister
Bacteroides

Revision editor(s): Aleru Divine

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-9-30

Curated date: 2024/05/05

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV- MASLD+
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants with Metabolic dysfunction-associated steatotic liver disease (MASLD) without HIV infection.
Group 1 sample size Number of subjects in the case (exposed) group
20

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-9-30

Curated date: 2024/05/05

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure S2

Description: LEfSe analysis graph indicating differentially abundant bacterial genera between the different study groups. Only those genus whose LDA score was greater than 4 have been represented.

Abundance in Group 1: increased abundance in HIV- MASLD+

NCBI Quality ControlLinks
Ruminiclostridium
Enterococcus
Pantoea
Clostridium sp. CAG:352
Yersinia
Lactobacillus
Ruminococcus
Streptococcus
Agathobacter
Escherichia/Shigella sp.
Anaerobutyricum hallii
Roseburia
Alistipes
Anaerostipes
Subdoligranulum
Weissella

Revision editor(s): Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-9-30

Curated date: 2024/05/05

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure S2

Description: LEfSe analysis graph indicating differentially abundant bacterial genera between the different study groups. Only those genus whose LDA score was greater than 4 have been represented.

Abundance in Group 1: decreased abundance in HIV- MASLD+

NCBI Quality ControlLinks
Acidaminococcus
Alloprevotella
Anaerovibrio
Asteroleplasma
Catenibacterium
Collinsella
Megasphaera
Mitsuokella
Parabacteroides
Paraprevotella
Phascolarctobacterium
Porphyromonas
Prevotella
Prevotella sp.
Prevotella sp. 2-3
Succinivibrio
Sutterella
Rikenellaceae RC9 gut groupRikenellaceae RC9 gut group
Prevotellaceae NK3B31 groupPrevotellaceae NK3B31 group
Prevotellaceae UCG-001Prevotellaceae UCG-001
Dialister
Bacteroides

Revision editor(s): Aleru Divine