Oral and gut microbial biomarkers of susceptibility to respiratory tract infection in adults: A feasibility study

Study information

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Reviewed Marked as Reviewed by Svetlana up on 2025-3-31

study design

time series / longitudinal observational
prospective cohort

Citation

PMID PubMed identifier for scientific articles.

37593638

DOI Digital object identifier for electronic documents.

10.1016/j.heliyon.2023.e18610

URI

Authors

Woodall CA, Hammond A, Cleary D, Preston A, Muir P, Pascoe B, Sheppard SK, Hay AD

Journal

Heliyon

Year

2023

Keywords:

Community, Feasibility, Longitudinal, Microbial biomarkers, Respiratory tract infection

We conducted a feasibility cohort study which aimed to recruit and retain adults from the community to collect saliva (oral) and stool (gut) samples at three time points, at the start of the study (baseline), during a respiratory tract infection (RTI) and post-RTI. Community RTIs place a huge burden on health care services, and a non-invasive microbial diagnostic tool to predict the most vulnerable to respiratory infection would be ideal. To this aim, we analysed oral-gut baseline samples comparing those who reported RTI symptoms to those who remained healthy throughout the study for microbial biomarkers of respiratory susceptibility. Amplicon sequence variants (ASV) were identified by 16S sequence profiling to reveal oral-gut microbes. Reverse transcriptase-polymerase chain reaction (RT-PCR) was applied to target common respiratory microbes. Two general practices were recruited, and the participant recruitment rate was 1.3%. A total of 40 adult participants were retained, of which 19 acquired an RTI whereas 21 remained healthy. In healthy baseline oral and gut samples, ASVs from participants with RTI symptoms compared to those who remained healthy were similar with a high relative abundance of Streptococcus sp., and Blautia sp., respectively. Linear discriminant analysis effect size (LEfSe) revealed baseline oral microbes differed, indicating participants who suffered RTI symptoms had enhanced Streptococcus sobrinus and Megamonas sp., and depletion of Lactobacillus salivarius, Synergistetes, Verrucomicrobia and Dethiosulfovibrio. Furthermore, a random forest model ranked Streptococcus (4.13) as the highest mean decrease in accuracy (MDA) and RT-PCR showed a higher level of carriage of coagulase-negative Staphylococcus. Baseline core gut microbes were similar in both participant groups whereas LEfSe analysis revealed enhanced Veillonella, Rikenellaceae, Enhydobacteria, Eggerthella and Xanthomonsdales and depleted Desulfobulbus and Coprobacillus. Sutterella (4.73) had a high MDA value. Overall, we demonstrated the feasibility of recruiting and retaining adult participants from the community to provide multiple biological samples for microbial profiling. Our analyses identified potential oral-gut microbial biomarkers of respiratory infection susceptibility in otherwise healthy participants.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2025-3-31

Curated date: 2025/03/22

Curator: UtibeIta

Revision editor(s): UtibeIta, Joiejoie

Subjects

Location of subjects

United Kingdom

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

Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Respiratory tract infectious disease infection, respiratory tract,infections, respiratory,infections, respiratory tract,infections, upper respiratory,infections, upper respiratory tract,respiratory infection, upper,respiratory infections,respiratory tract infection,upper respiratory infections,upper respiratory tract infections,Respiratory tract infectious disease,respiratory tract infectious disease

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

respiratory tract infection(baseline)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

participants who acquired Respiratory Tract Infection symptoms at the baseline/start of the study

Group 0 sample size Number of subjects in the control (unexposed) group

21

Group 1 sample size Number of subjects in the case (exposed) group

19

Lab analysis

Sequencing type

16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

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)?

No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool

2

Alpha Diversity

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

unchanged

Chao1 Abundance-based estimator of species richness

unchanged

Signature 1

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Curator: UtibeIta

Revision editor(s): UtibeIta

Source: Figure 5

Description: Difference between microbial biomarkers in oral baseline samples from participants who acquired Respiratory Tract Infection symptoms compared to those who remained healthy.

Abundance in Group 1: increased abundance in respiratory tract infection(baseline)

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Megamonas
Megamonas sp.
Streptococcus sobrinus

Revision editor(s): UtibeIta

Signature 2

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Revision editor(s): UtibeIta

Source: Figure 5

Description: Difference between microbial biomarkers in oral baseline samples from participants who acquired Respiratory Tract Infection symptoms compared to those who remained healthy.

Abundance in Group 1: decreased abundance in respiratory tract infection(baseline)

NCBI	Quality Control	Links
Dethiosulfovibrio
Lactobacillus sp.
Ligilactobacillus salivarius
Synergistota
Verrucomicrobiota
uncultured Synergistia bacterium

Revision editor(s): UtibeIta

Experiment 2

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Curated date: 2025/03/22

Curator: UtibeIta

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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

Lab analysis

Statistical Analysis

Alpha Diversity

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

unchanged

Chao1 Abundance-based estimator of species richness

unchanged

Signature 1

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Curated date: 2025/03/25

Curator: UtibeIta

Revision editor(s): UtibeIta

Source: Figure 5

Description: Difference between microbial biomarkers in gut baseline samples from participants who acquired Respiratory Tract Infection symptoms compared to those who remained healthy.

Abundance in Group 1: increased abundance in respiratory tract infection(baseline)

NCBI	Quality Control	Links
Eggerthella sp.
Enhydrobacter
Enhydrobacter sp.
Lysobacteraceae
Lysobacterales
Rikenellaceae
Veillonella sp.

Revision editor(s): UtibeIta

Signature 2

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Curated date: 2025/03/25

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Revision editor(s): UtibeIta

Source: Figure 5

Description: Difference between microbial biomarkers in gut baseline samples from participants who acquired Respiratory Tract Infection symptoms compared to those who remained healthy.

Abundance in Group 1: decreased abundance in respiratory tract infection(baseline)

NCBI	Quality Control	Links
Coprobacillus sp.
Desulfobacterales
Desulfobulbaceae
Desulfobulbus
Desulfobulbus sp.

Revision editor(s): UtibeIta

Experiment 3

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Curated date: 2025/03/27

Curator: UtibeIta

Revision editor(s): UtibeIta

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology

Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva

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

respiratory tract infection(end of study)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

participants who acquired Respiratory Tract Infection symptoms at the end of study

Group 1 sample size Number of subjects in the case (exposed) group

17

Lab analysis

Statistical Analysis

Alpha Diversity

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

decreased

Chao1 Abundance-based estimator of species richness

decreased

Signature 1

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Reviewed Marked as Reviewed by Svetlana up on 2025-3-31

Curated date: 2025/03/27

Curator: UtibeIta

Revision editor(s): UtibeIta

Source: Figure S3A

Description: Difference between microbial biomarkers in oral end-of-study samples from participants who acquired Respiratory Tract Infection symptoms compared to those who remained healthy.

Abundance in Group 1: increased abundance in respiratory tract infection(end of study)

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Actinomycetales
Actinomycetota
Bacilli
Lactobacillus
Streptococcaceae
Streptococcus

Revision editor(s): UtibeIta

Signature 2

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Curated date: 2025/03/27

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Revision editor(s): UtibeIta

Source: Figure S3A

Description: Difference between microbial biomarkers in oral end-of-study samples from participants who acquired Respiratory Tract Infection symptoms compared to those who remained healthy.

Abundance in Group 1: decreased abundance in respiratory tract infection(end of study)

NCBI	Quality Control	Links
Clostridia
Eubacteriales
Oscillospiraceae

Revision editor(s): UtibeIta

Experiment 4

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Curated date: 2025/03/27

Curator: UtibeIta

Revision editor(s): UtibeIta

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

Lab analysis

Statistical Analysis

Alpha Diversity

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

unchanged

Chao1 Abundance-based estimator of species richness

unchanged

Signature 1

EditHistoryDelete

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Reviewed Marked as Reviewed by Svetlana up on 2025-3-31

Curated date: 2025/03/27

Curator: UtibeIta

Revision editor(s): UtibeIta, Aleru Divine

Source: Figure S3B

Description: Difference between microbial biomarkers in gut end-of-study samples from participants who acquired Respiratory Tract Infection symptoms compared to those who remained healthy.

Abundance in Group 1: increased abundance in respiratory tract infection(end of study)

NCBI	Quality Control	Links
Catenibacterium
Catenibacterium sp.
Clostridia
[Ruminococcus] torques
Clostridia bacterium

Revision editor(s): UtibeIta, Aleru Divine

Signature 2

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Reviewed Marked as Reviewed by Svetlana up on 2025-3-31

Curated date: 2025/03/27

Curator: UtibeIta

Revision editor(s): UtibeIta

Source: Figure S3B

Description: Difference between microbial biomarkers in gut end-of-study samples from participants who acquired Respiratory Tract Infection symptoms compared to those who remained healthy.

Abundance in Group 1: decreased abundance in respiratory tract infection(end of study)

NCBI	Quality Control	Links
Coprobacillus
Erysipelotrichales
Erysipelotrichaceae
Eubacterium
Eubacterium sp.
Holdemanella biformis

Revision editor(s): UtibeIta