Distinct intestinal microbial signatures linked to accelerated systemic and intestinal biological aging

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Singh S, Giron LB, Shaikh MW, Shankaran S, Engen PA, Bogin ZR, Bambi SA, Goldman AR, Azevedo JLLC, Orgaz L, de Pedro N, González P, Giera M, Verhoeven A, Sánchez-López E, Pandrea I, Kannan T, Tanes CE, Bittinger K, Landay AL, Corley MJ, Keshavarzian A, Abdel-Mohsen M
Journal
Microbiome
Year
2024
Keywords:
Aging clocks, Biological aging, Gut, HIV, Intestines, Metabolome, Microbiome
BACKGROUND: People living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed to intestinal microbial dysbiosis and translocation, which may lead to non-AIDS-related aging-associated comorbidities. The extent to which living with HIV - influenced by the infection itself, ART usage, sexual orientation, or other associated factors - affects the biological age of the intestines is unclear. Furthermore, the role of microbial dysbiosis and translocation in the biological aging of PLWH remains to be elucidated. To investigate these uncertainties, we used a systems biology approach, analyzing colon and ileal biopsies, blood samples, and stool specimens from PLWH on ART and people living without HIV (PLWoH) as controls. RESULTS: PLWH exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to PLWoH. Investigating the relationship between microbial translocation and biological aging, PLWH had decreased levels of tight junction proteins in the intestines, along with increased microbial translocation. This intestinal permeability correlated with faster biological aging and increased inflammation. When investigating the relationship between microbial dysbiosis and biological aging, the intestines of PLWH had higher abundance of specific pro-inflammatory bacteria, such as Catenibacterium and Prevotella. These bacteria correlated with accelerated biological aging. Conversely, the intestines of PLWH had lower abundance of bacteria known for producing the anti-inflammatory short-chain fatty acids, such as Subdoligranulum and Erysipelotrichaceae, and these bacteria were associated with slower biological aging. Correlation networks revealed significant links between specific microbial genera in the colon and ileum (but not in feces), increased aging, a rise in pro-inflammatory microbe-related metabolites (e.g., those in the tryptophan metabolism pathway), and a decrease in anti-inflammatory metabolites like hippuric acid. CONCLUSIONS: We identified specific microbial compositions and microbiota-related metabolic pathways that are intertwined with intestinal and systemic biological aging. This microbial signature of biological aging is likely reflecting various factors including the HIV infection itself, ART usage, sexual orientation, and other aspects associated with living with HIV. A deeper understanding of the mechanisms underlying these connections could offer potential strategies to mitigate accelerated aging and its associated health complications. Video Abstract.

Experiment 1


Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Subjects

Location of subjects
United States of America
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
Colon Hindgut,Large bowel,Posterior intestine,Colon,colon
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Aging ageing,AGING BIOL,Aging, Biological,BIOL AGING,Biological Aging,Senescence,Aging,aging
Group 0 name Corresponds to the control (unexposed) group for case-control studies
PLWOH
Group 1 name Corresponds to the case (exposed) group for case-control studies
PLWH on ART
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
People living with HIV(PLWH) on Anti-Retroviral Therapy(ART)
Group 0 sample size Number of subjects in the control (unexposed) group
23
Group 1 sample size Number of subjects in the case (exposed) group
25
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Not stated

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V1-V2
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
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)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
age, body mass index, ethnic group, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Richness Number of species
decreased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
decreased

Signature 1

Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Source: Fig 4D

Description: Log-scale differences in bacterial abundance across colon (triangle), ileum (square), and feces (circle) between PLWoH and PLWH on ART.

Abundance in Group 1: increased abundance in PLWH on ART

NCBI Quality ControlLinks
Alloprevotella
Catenibacterium
Prevotella 2Prevotella 2

Revision editor(s): Imaspecial

Signature 2

Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Source: Fig 4D

Description: Log-scale differences in bacterial abundance across colon (triangle), ileum (square), and feces (circle) between PLWoH and PLWH on ART.

Abundance in Group 1: decreased abundance in PLWH on ART

NCBI Quality ControlLinks
Alistipes
Bacteroides
Faecalibacterium
uncultured Erysipelotrichaceae bacterium
Coprococcus 3Coprococcus 3

Revision editor(s): Imaspecial

Experiment 2


Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Ileum Distal intestine,Intestinum ileum,Lower intestine,Posterior intestine,Ileum,ileum


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
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Source: Fig 4D

Description: Log-scale differences in bacterial abundance across colon (triangle), ileum (square), and feces (circle) between PLWoH and PLWH on ART.

Abundance in Group 1: increased abundance in PLWH on ART

NCBI Quality ControlLinks
Alloprevotella
Catenibacterium
Prevotella 2Prevotella 2
Prevotella 9Prevotella 9

Revision editor(s): Imaspecial

Signature 2

Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Source: Fig 4D

Description: Log-scale differences in bacterial abundance across colon (triangle), ileum (square), and feces (circle) between PLWOH and PLWH on ART

Abundance in Group 1: decreased abundance in PLWH on ART

NCBI Quality ControlLinks
Alistipes
Bacteroides
Subdoligranulum
uncultured Erysipelotrichaceae bacterium
Coprococcus 3Coprococcus 3

Revision editor(s): Imaspecial

Experiment 3


Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Differences from previous experiment shown

Subjects

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
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
People living with HIV(PLWH) on Anti-Retroviral Therapy (ART)

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
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Source: Fig 4D

Description: Log-scale differences in bacterial abundance across colon (triangle), ileum (square), and feces (circle) between PLWOH and PLWH on ART.

Abundance in Group 1: increased abundance in PLWH on ART

NCBI Quality ControlLinks
Catenibacterium
Lachnospiraceae

Revision editor(s): Imaspecial

Signature 2

Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Source: Fig 4D

Description: Log-scale differences in bacterial abundance across colon (triangle), ileum (square), and feces (circle) between PLWOH and PLWH on ART.

Abundance in Group 1: decreased abundance in PLWH on ART

NCBI Quality ControlLinks
uncultured Erysipelotrichaceae bacterium

Revision editor(s): Imaspecial

Experiment 4


Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Colon , Feces Hindgut,Large bowel,Posterior intestine,Colon,colon,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
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Samples of PLWOH
Group 1 name Corresponds to the case (exposed) group for case-control studies
Samples PLWH on ART
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Colon vs fecal samples of People living with HIV on ART

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Source: Fig 4C

Description: Differential bacterial abundance between tissue and fecal samples on a logarithmic scale. Comparisons include colon vs. feces (red), ileum vs. feces (blue), and ileum vs. colon (green).

Abundance in Group 1: increased abundance in Samples PLWH on ART

NCBI Quality ControlLinks
Agathobacter
Anaerobutyricum hallii
Anaerostipes
Blautia
Catenibacterium
Collinsella
Fusicatenibacter
Holdemanella
Peptostreptococcaceae
Romboutsia
Ruminococcus gauvreauii
Streptococcus
uncultured Erysipelotrichaceae bacterium
Ruminococcus 2Ruminococcus 2

Revision editor(s): Imaspecial

Signature 2

Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Source: Fig 4C

Description: Differential bacterial abundance between tissue and fecal samples on a logarithmic scale. Comparisons include colon vs. feces (red), ileum vs. feces (blue), and ileum vs. colon (green).

Abundance in Group 1: decreased abundance in Samples PLWH on ART

NCBI Quality ControlLinks
Alistipes
Alloprevotella
Bacteroides
Enterobacteriaceae
Fusobacterium
Lachnoclostridium
Mediterraneibacter gnavus
Parabacteroides
Sutterella
[Ruminococcus] torques
uncultured Firmicutes bacterium
Prevotella 2Prevotella 2
Prevotella 9Prevotella 9

Revision editor(s): Imaspecial

Experiment 5


Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Ileum , Feces Distal intestine,Intestinum ileum,Lower intestine,Posterior intestine,Ileum,ileum,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
Group 1 name Corresponds to the case (exposed) group for case-control studies
Samples of PLWH on ART
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Ileum vs Feces of people living with HIV on ART

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Source: Fig 4C

Description: Differential bacterial abundance between tissue and fecal samples on a logarithmic scale. Comparisons include colon vs. feces (red), ileum vs. feces (blue), and ileum vs. colon (green).

Abundance in Group 1: increased abundance in Samples of PLWH on ART

NCBI Quality ControlLinks
Agathobacter
Anaerobutyricum hallii
Anaerostipes
Blautia
Catenibacterium
Collinsella
Dorea
Fusicatenibacter
Holdemanella
Peptostreptococcaceae
Romboutsia
Ruminococcus gauvreauii
uncultured Erysipelotrichaceae bacterium
Ruminococcus 2Ruminococcus 2

Revision editor(s): Imaspecial

Signature 2

Needs review

Curated date: 2024/03/22

Curator: Imaspecial

Revision editor(s): Imaspecial

Source: Fig 4C

Description: Differential bacterial abundance between tissue and fecal samples on a logarithmic scale. Comparisons include colon vs. feces (red), ileum vs. feces (blue), and ileum vs. colon (green).

Abundance in Group 1: decreased abundance in Samples of PLWH on ART

NCBI Quality ControlLinks
Alistipes
Alloprevotella
Bacteroides
Enterobacteriaceae
Fusobacterium
Lachnoclostridium
Mediterraneibacter gnavus
Parabacteroides
Sutterella
[Ruminococcus] torques
Prevotella 2Prevotella 2
Prevotella 9Prevotella 9

Revision editor(s): Imaspecial