Dynamics of Gut Microbiota Recovery after Antibiotic Exposure in Young and Old Mice (A Pilot Study)

Study information

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

33804656

DOI Digital object identifier for electronic documents.

10.3390/microorganisms9030647

URI

Authors

Laubitz D, Typpo K, Midura-Kiela M, Brown C, Barberán A, Ghishan FK, Kiela PR

Journal

Microorganisms

Year

2021

Keywords:

16S, aging, antibiotics, bacteria, ciprofloxacin, metronidazole

Antibiotics have improved survival from previously deadly infectious diseases. Antibiotics alter the microbial composition of the gut microbiota, and these changes are associated with diminished innate immunity and decline in cognitive function in older adults. The composition of the human microbiota changes with age over the human lifespan. In this pilot study, we sought to identify if age is associated with differential recovery of the microbiota after antibiotic exposure. Using 16S rRNA gene sequencing, we compared recovery of the gut microbiota after the 10-day broad-spectrum antibiotic treatment in wild-type C57BL/six young and older mice. Immediately after antibiotic cessation, as expected, the number of ASVs, representing taxonomic richness, in both young and older mice significantly declined from the baseline. Mice were followed up to 6 months after cessation of the single 10-day antibiotic regimen. The Bray-Curtis index recovered within 20 days after antibiotic cessation in young mice, whereas in older mice the microbiota did not fully recover during the 6-months of follow-up. Bifidobacterium, Dubosiella, Lachnospiraceae_NK4A136_group became dominant in older mice, whereas in young mice, the bacteria were more evenly distributed, with only one dominant genus of Anaeroplasma. From 45 genera that became extinct after antibiotic treatment in young mice, 31 (68.9%) did not recover by the end of the study. In older mice, from 36 extinct genera, 27 (75%) did not recover. The majority of the genera that became extinct and never recovered belonged to Firmicutes phylum and Clostridiales family. In our study, age was a factor associated with the long-term recovery of the gut microbiota after the 10-day antibiotic treatment.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/27

Curator: Gina

Revision editor(s): WikiWorks, LGeistlinger, Claregrieve1, Gina, Peace Sandy

Subjects

Location of subjects

United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.

Mus musculus

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

Antimicrobial agent antibiotic,antibiotics,Antibiotika,Antibiotikum,antibiotique,antimicrobial,antimicrobial agents,microbicide,microbicides,Antimicrobial agent,antimicrobial agent

Group 0 name Corresponds to the control (unexposed) group for case-control studies

7 week old (young) mice before antibiotic treatment

Group 1 name Corresponds to the case (exposed) group for case-control studies

7 week old (young) mice 10 days after antibiotic treatments

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

7-week old mice (young mice) administered treated with broad-spectrum antibiotics metronidazole (500 mg/L) and ciprofloxacin (200 mg/L) for 10 days.

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

5

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

5

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)

Mice were not previously given antibiotics before the study

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)?

Yes

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment

sex

Alpha Diversity

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

decreased

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

decreased

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/27

Curator: Gina

Revision editor(s): Gina

Source: Figure 5

Description: Linear discriminant analysis (LDA) effect size (LEfSe) of differentially abundant bacterial taxa between young mice after 10 days of antibiotic treatment

Abundance in Group 1: increased abundance in 7 week old (young) mice 10 days after antibiotic treatments

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Enterococcaceae
Lactobacillales
Enterococcus

Revision editor(s): Gina

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/28

Curator: Gina

Revision editor(s): Gina

Source: Figure 5

Description: Linear discriminant analysis (LDA) effect size (LEfSe) of differentially abundant bacterial taxa between young after 10 days of Abx treatment

Abundance in Group 1: decreased abundance in 7 week old (young) mice 10 days after antibiotic treatments

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Candidatus Stoquefichus
Clostridiales Family XIII bacterium
Erysipelotrichaceae
Erysipelotrichales
Faecalibaculum
Peptostreptococcaceae
Romboutsia
Clostridiales bacterium

Revision editor(s): Gina

Experiment 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/29

Curator: Gina

Revision editor(s): WikiWorks, LGeistlinger, Claregrieve1, Gina, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

7 week old (young) mice 6 months after antibiotic treatments

Lab analysis

Statistical Analysis

Alpha Diversity

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

decreased

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

decreased

Signature 1

EditHistoryDelete

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/29

Curator: Gina

Revision editor(s): Gina

Source: Figure 5

Description: Linear discriminant analysis (LDA) effect size (LEfSe) of differentially abundant bacterial taxa between young after 6 months of recovery

Abundance in Group 1: increased abundance in 7 week old (young) mice 6 months after antibiotic treatments

NCBI	Quality Control	Links
Romboutsia
Peptostreptococcaceae
Dubosiella

Revision editor(s): Gina

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/29

Curator: Gina

Revision editor(s): Gina

Source: Figure 5

Description: Linear discriminant analysis (LDA) effect size (LEfSe) of differentially abundant bacterial taxa between young after 6 months of recovery (lower panels)

Abundance in Group 1: decreased abundance in 7 week old (young) mice 6 months after antibiotic treatments

NCBI	Quality Control	Links
Clostridiales Family XIII bacterium
Candidatus Stoquefichus

Revision editor(s): Gina

Experiment 3

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/29

Curator: Gina

Revision editor(s): WikiWorks, LGeistlinger, Claregrieve1, Gina, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

40 week old (old) mice before antibiotic treatment

Group 1 name Corresponds to the case (exposed) group for case-control studies

40 week old (old) mice 10 days after antibiotic treatments

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

40-week old mice (old) administered treated with broad-spectrum antibiotics metronidazole (500 mg/L) and ciprofloxacin (200 mg/L) for 10 days.

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

Signature 1

EditHistoryDelete

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/29

Curator: Gina

Revision editor(s): Gina

Source: Figure 5

Description: Linear discriminant analysis (LDA) effect size (LEfSe) of differentially abundant bacterial taxa between older mice (right panels) after 10 days of Abx treatment

Abundance in Group 1: increased abundance in 40 week old (old) mice 10 days after antibiotic treatments

NCBI	Quality Control	Links
Bacteroidales

Revision editor(s): Gina

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/29

Curator: Gina

Revision editor(s): Gina

Source: Figure 5

Description: Linear discriminant analysis (LDA) effect size (LEfSe) of differentially abundant bacterial taxa between older mice (right panels) after 10 days of Abx treatment.

Abundance in Group 1: decreased abundance in 40 week old (old) mice 10 days after antibiotic treatments

NCBI	Quality Control	Links
Romboutsia
Peptostreptococcaceae
Faecalibaculum
Erysipelotrichaceae
Erysipelotrichales

Revision editor(s): Gina

Experiment 4

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/29

Curator: Gina

Revision editor(s): WikiWorks, LGeistlinger, Claregrieve1, Gina, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

40 week old (old) mice 6 months after antibiotic treatments

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

Signature 1

EditHistoryDelete

Flag for review

Your review change was submitted

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/29

Curator: Gina

Revision editor(s): Gina

Source: Figure 5

Description: Linear discriminant analysis (LDA) effect size (LEfSe) of differentially abundant bacterial taxa between older mice (right panels) after 6 months of recovery (lower panels).

Abundance in Group 1: decreased abundance in 40 week old (old) mice 6 months after antibiotic treatments

NCBI	Quality Control	Links
Bacteroidales
Faecalibaculum
Muribaculaceae
Muribaculum
Peptostreptococcaceae
Romboutsia
Clostridiales bacterium

Revision editor(s): Gina

Signature 2

EditHistoryDelete

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/27

Curated date: 2021/09/29

Curator: Gina

Revision editor(s): Gina

Source: Figure 5

Description: Linear discriminant analysis (LDA) effect size (LEfSe) of differentially abundant bacterial taxa between older mice after 6 months of recovery

Abundance in Group 1: increased abundance in 40 week old (old) mice 6 months after antibiotic treatments

NCBI	Quality Control	Links
Dubosiella
Erysipelotrichaceae
Erysipelotrichales

Revision editor(s): Gina