Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Brito Rodrigues P, de Rezende Rodovalho V, Sencio V, Benech N, Creskey M, Silva Angulo F, Delval L, Robil C, Gosset P, Machelart A, Haas J, Descat A, Goosens JF, Beury D, Maurier F, Hot D, Wolowczuk I, Sokol H, Zhang X, Ramirez Vinolo MA, Trottein F
Journal
Gut microbes
Year
2025
Keywords:
SARS-CoV-2, Viral pneumonia, aging, disease markers, gut microbiota, metabolomics, metagenomics
Aging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-old) and aged (22-month-old) hamsters, a valuable model of COVID-19. We show that age-related dysfunctions in the gut microbiota are linked to disease severity and long-term sequelae in older hamsters. Our data also reveal age-specific changes in the composition and metabolic activity of the gut microbiota during both the acute phase (day 7 post-infection, D7) and the recovery phase (D22) of infection. Aged hamsters exhibited the most notable shifts in gut microbiota composition and plasma metabolic profiles. Through an integrative analysis of metagenomics, metabolomics, and clinical data, we identified significant associations between bacterial taxa, metabolites and disease markers in the aged group. On D7 (high viral load and lung epithelial damage) and D22 (body weight loss and fibrosis), numerous amino acids, amino acid-related molecules, and indole derivatives were found to correlate with disease markers. In particular, a persistent decrease in phenylalanine, tryptophan, glutamic acid, and indoleacetic acid in aged animals positively correlated with poor recovery of body weight and/or lung fibrosis by D22. In younger hamsters, several bacterial taxa (Eubacterium, Oscillospiraceae, Lawsonibacter) and plasma metabolites (carnosine and cis-aconitic acid) were associated with mild disease outcomes. These findings support the need for age-specific microbiome-targeting strategies to more effectively manage acute viral pneumonia and long-term disease outcomes.

Experiment 1


Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Subjects

Location of subjects
France
Host species Species from which microbiome was sampled. Contact us to have more species added.
Mesocricetus auratus
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Caecum Blind intestine,Blindgut,Caeca,Caecum,Ceca,Cecum,Intestinum caecum,Intestinum crassum caecum,Intestinum crassum cecum,caecum
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Age Age,age
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Young Hamsters
Group 1 name Corresponds to the case (exposed) group for case-control studies
Aged Hamsters
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Hamsters in the aged group were 22 months old.
Group 0 sample size Number of subjects in the control (unexposed) group
3
Group 1 sample size Number of subjects in the case (exposed) group
6

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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
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)?
Yes

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 1C

Description: Differential abundance of taxa between Young and Aged hamsters analyzed with Maaslin2 (adjusted P-value < 0.05).

Abundance in Group 1: increased abundance in Aged Hamsters

NCBI Quality ControlLinks
Alistipes
Alistipes onderdonkii
Bifidobacterium animalis
Firmicutes bacterium CAG:95
Lactobacillales
Ligilactobacillus
Ligilactobacillus murinus
Paramuribaculum
Parasutterella sp.
Prevotella sp. CAG:873
uncultured Alistipes sp.
UBA7173UBA7173
Porphyromonadaceae bacterium UBA7173

Revision editor(s): MyleeeA

Signature 2

Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 1C

Description: Differential abundance of taxa between Young and Aged hamsters analyzed with Maaslin2 (adjusted P-value < 0.05).

Abundance in Group 1: decreased abundance in Aged Hamsters

NCBI Quality ControlLinks
Acetatifactor
Clostridium sp. CAG:127
Cutibacterium modestum
Ruminiclostridium ERuminiclostridium E
UBA9502UBA9502
Lachnospiraceae bacterium MD335
Lachnospiraceae bacterium

Revision editor(s): MyleeeA

Experiment 2


Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
SARS-CoV-2-related disease COVID-19-related disease,SARS-CoV-2-related disease,sARS-CoV-2-related disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Young and Aged D0 non-infected controls (Age effect)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Young and Aged D7 Infected (Age effect)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Young (2 months old) and Aged (22 months old) SARS-CoV-2-infected hamsters at Day 7 with age effect.
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 Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3C

Description: Differential abundance of taxa between Young and Aged D0 non-infected controls (Age effect) and Young and Aged D7 Infected (Age effect) hamsters analyzed with Maaslin2 (adjusted P-value < 0.05).

Abundance in Group 1: increased abundance in Young and Aged D7 Infected (Age effect)

NCBI Quality ControlLinks
Bacteroides
Bifidobacterium
Eggerthellaceae
Ligilactobacillus
Odoribacter
Rikenella
Streptococcus
NM07_P.09NM07_P.09
RIkenellaceae NOVRIkenellaceae NOV
Faecalibacterium

Revision editor(s): MyleeeA

Signature 2

Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3C

Description: Differential abundance of taxa between Young and Aged D0 non-infected controls (Age effect) and Young and Aged D7 Infected (Age effect) hamsters analyzed with Maaslin2 (adjusted P-value < 0.05).

Abundance in Group 1: decreased abundance in Young and Aged D7 Infected (Age effect)

NCBI Quality ControlLinks
Acetatifactor
Anaerostipes
Bacilli
Blautia
Eisenbergiella
Eubacterium sp. CAG:115
Eubacterium sp. CAG:180
Firmicutes bacterium CAG:475
Firmicutes bacterium CAG:582
Firmicutes bacterium CAG:822
Frisingicoccus
Granulicatella
Kineothrix
Lachnospiraceae bacterium
Roseburia
Roseburia sp. CAG:303
Turicimonas
unclassified Lachnospiraceae
UMGS1071UMGS1071
Erysipelotrichaceae NOVErysipelotrichaceae NOV
Helicobacter DHelicobacter D
Ruminococcus CRuminococcus C
UMGS1217UMGS1217
UBA7057UBA7057
Ruminiclostridium ERuminiclostridium E
Helicobacter AHelicobacter A
Helicobacter CHelicobacter C
Butyrivibrio AButyrivibrio A
CAG:518CAG:518

Revision editor(s): MyleeeA

Experiment 3


Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Young and Aged D0 non-infected controls (Time effect)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Young and Aged D7 Infected (Time effect)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Young (2 months old) and Aged (22 months old) SARS-CoV-2-infected hamsters at Day 7 of infection with time of infection effect.

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3C

Description: Differential abundance of taxa between Young and Aged D0 non-infected controls (Time effect) and Young and Aged D7 Infected (Time effect) hamsters analyzed with Maaslin2 (adjusted P-value < 0.05).

Abundance in Group 1: increased abundance in Young and Aged D7 Infected (Time effect)

NCBI Quality ControlLinks
Adlercreutzia
Bacteroides
Clostridium sp. CAG:273
Faecalibacterium sp. UBA7177
Firmicutes bacterium CAG:822
Limosilactobacillus
Parabacteroides
Phocaeicola
Ruthenibacterium
Thomasclavelia
UBA1820UBA1820
UBA2882UBA2882
UBA3789UBA3789
UBA1436UBA1436
CAG:776CAG:776
CAG:611 NOVCAG:611 NOV
UMGS995UMGS995
CAG:822 NOVCAG:822 NOV
UBA2730UBA2730
Christensenellales NOVChristensenellales NOV

Revision editor(s): MyleeeA

Signature 2

Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3C

Description: Differential abundance of taxa between Young and Aged D0 non-infected controls (Time effect) and Young and Aged D7 Infected (Time effect) hamsters analyzed with Maaslin2 (adjusted P-value < 0.05).

Abundance in Group 1: decreased abundance in Young and Aged D7 Infected (Time effect)

NCBI Quality ControlLinks
Acetobacter sp. CAG:267
Allobaculum
Angelakisella
Eubacterium sp. CAG:180
Frisingicoccus
Helicobacteraceae
Ileibacterium
Ligilactobacillus
Longicatena
Mucispirillum
Muribaculaceae
Prevotellamassilia
UBA7185UBA7185
Erysipelotrichaceae NOVErysipelotrichaceae NOV
Hungetella AHungetella A
UMGS1872UMGS1872
Butyricicoccaceae NOVButyricicoccaceae NOV
Eubacterium JEubacterium J
UBA1405UBA1405
Clostridium QClostridium Q
CAG:950CAG:950
Mycoplasmoidaceae NOVMycoplasmoidaceae NOV
Lachnospiraceae bacterium UBA7182

Revision editor(s): MyleeeA

Experiment 4


Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Young and Aged D0 non-infected controls (Age effect)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Young and Aged D22 Infected (Age effect)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Young (2 months old) and Aged (22 months old) SARS-CoV-2-infected hamsters at Day 22 with age effect.

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3D

Description: Differential abundance of taxa between Young and Aged D0 non-infected controls (Age effect) and Young and Aged D22 Infected (Age effect) hamsters analyzed with Maaslin2 (adjusted P-value < 0.05).

Abundance in Group 1: increased abundance in Young and Aged D22 Infected (Age effect)

NCBI Quality ControlLinks
Duncaniella
Eubacterium sp. CAG:180
Lachnospiraceae
Prevotella sp. CAG:873
Rikenella
Streptococcus
CAG:594CAG:594
Lachnospiraceae NOVLachnospiraceae NOV
X1XD42.69X1XD42.69
Muribaculaceae NOVMuribaculaceae NOV
Rikenellaceae NOVRikenellaceae NOV
UBA3263UBA3263
Anaerovoracaceae NOVAnaerovoracaceae NOV

Revision editor(s): MyleeeA

Signature 2

Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3D

Description: Differential abundance of taxa between Young and Aged D0 non-infected controls (Age effect) and Young and Aged D22 Infected (Age effect) hamsters analyzed with MaAslin2 (adjusted P-value < 0.05).

Abundance in Group 1: decreased abundance in Young and Aged D22 Infected (Age effect)

NCBI Quality ControlLinks
Clostridium sp. CAG:127
Clostridium sp. CAG:510
Lachnospiraceae bacterium

Revision editor(s): MyleeeA

Experiment 5


Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Young and Aged D0 non-infected controls (Time effect)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Young and Aged D22 Infected (Time effect)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Young (2 months old) and Aged (22 months old) SARS-CoV-2-infected hamsters at Day 22 of infection with time of infection effect.

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/05/04

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3D

Description: Differential abundance of taxa between Young and Aged D0 non-infected controls (Time effect) and Young and Aged D22 Infected (Time effect) hamsters analyzed with MaAslin2 (adjusted P-value < 0.05).

Abundance in Group 1: decreased abundance in Young and Aged D22 Infected (Time effect)

NCBI Quality ControlLinks
Allobaculum
Anaerotignum
Angelakisella
Dubosiella
Enterococcus
Leuconostoc
Longicatena
Mailhella
Muribaculaceae
Odoribacter
Parvibacter
Proteobacteria bacterium CAG:495
Paenibacillus APaenibacillus A
Marseile.P3106Marseile.P3106
Mycoplasmoidaceae NOVMycoplasmoidaceae NOV
Gastranaerophilales NOVGastranaerophilales NOV

Revision editor(s): MyleeeA