High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin

From BugSigDB
Reviewed Marked as Reviewed by Chloe on 2021/11/18
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Fouhy F, Guinane CM, Hussey S, Wall R, Ryan CA, Dempsey EM, Murphy B, Ross RP, Fitzgerald GF, Stanton C, Cotter PD
Journal
Antimicrobial agents and chemotherapy
Year
2012
The infant gut microbiota undergoes dramatic changes during the first 2 years of life. The acquisition and development of this population can be influenced by numerous factors, and antibiotic treatment has been suggested as one of the most significant. Despite this, however, there have been relatively few studies which have investigated the short-term recovery of the infant gut microbiota following antibiotic treatment. The aim of this study was to use high-throughput sequencing (employing both 16S rRNA and rpoB-specific primers) and quantitative PCR to compare the gut microbiota of nine infants who underwent parenteral antibiotic treatment with ampicillin and gentamicin (within 48 h of birth), 4 and 8 weeks after the conclusion of treatment, relative to that of nine matched healthy controls. The investigation revealed that the gut microbiota of the antibiotic-treated infants had significantly higher proportions of Proteobacteria (P = 0.0049) and significantly lower proportions of Actinobacteria (P = 0.00001) (and the associated genus Bifidobacterium [P = 0.0132]) as well as the genus Lactobacillus (P = 0.0182) than the untreated controls 4 weeks after the cessation of treatment. By week 8, the Proteobacteria levels remained significantly higher in the treated infants (P = 0.0049), but the Actinobacteria, Bifidobacterium, and Lactobacillus levels had recovered and were similar to those in the control samples. Despite this recovery of total Bifidobacterium numbers, rpoB-targeted pyrosequencing revealed that the number of different Bifidobacterium species present in the antibiotic-treated infants was reduced. It is thus apparent that the combined use of ampicillin and gentamicin in early life can have significant effects on the evolution of the infant gut microbiota, the long-term health implications of which remain unknown.

Experiment 1


Reviewed Marked as Reviewed by Chloe on 2021/11/18

Curated date: 2021/10/01

Curator: Mmarin

Revision editor(s): WikiWorks, LGeistlinger, Mmarin, Peace Sandy

Subjects

Location of subjects
Ireland
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
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
Untreated controls (week 4)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Antibiotic treated (week 4)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Had received parenteral antibiotic treatment with a combination of ampicillin and gentamicin within 48 hours of birth
Group 0 sample size Number of subjects in the control (unexposed) group
9
Group 1 sample size Number of subjects in the case (exposed) group
9
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
excluded if they required oral antibiotics (no time frame given)

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
Roche454

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

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

Reviewed Marked as Reviewed by Chloe on 2021/11/18

Curated date: 2021/10/07

Curator: Mmarin

Revision editor(s): Mmarin

Source: Figure 1, Figure 2, Figure 3

Description: Figure 1: Microbial distributions at the phylum level in the samples from treated and control infants at week 4 and week 8. Statistically significant differences between treated infants and controls at week 4 are indicated by asterisks (P < 0.05). Percentages are based on proportions of assignable tags.

Figure 2: Microbial distributions at the family level in the samples from treated and control infants at week 4 and week 8. Statistically significant differences between treated infants and controls at week 4 are indicated by asterisks (P < 0.05). Percentages are based on proportions of assignable reads.

Figure 3: Microbial distributions at the genus level in the samples from treated and control infants at week 4 and week 8. Statistically significant differences between treated infants and controls at week 4 are indicated by asterisks (P < 0.05). Percentages are based on proportions of assignable reads.

Abundance in Group 1: increased abundance in Antibiotic treated (week 4)

NCBI Quality ControlLinks
Enterobacteriaceae
Lactobacillaceae
Peptostreptococcaceae
Pseudomonadota
unclassified Enterobacteriaceae

Revision editor(s): Mmarin

Signature 2

Reviewed Marked as Reviewed by Chloe on 2021/11/18

Curated date: 2021/10/07

Curator: Mmarin

Revision editor(s): Mmarin

Source: Figure 1, Figure 2, Figure 3

Description: Figure 1: Microbial distributions at the phylum level in the samples from treated and control infants at week 4 and week 8. Statistically significant differences between treated infants and controls at week 4 are indicated by asterisks (P < 0.05). Percentages are based on proportions of assignable tags.

Figure 2: Microbial distributions at the family level in the samples from treated and control infants at week 4 and week 8. Statistically significant differences between treated infants and controls at week 4 are indicated by asterisks (P < 0.05). Percentages are based on proportions of assignable reads.

Figure 3: Microbial distributions at the genus level in the samples from treated and control infants at week 4 and week 8. Statistically significant differences between treated infants and controls at week 4 are indicated by asterisks (P < 0.05). Percentages are based on proportions of assignable reads.

Abundance in Group 1: decreased abundance in Antibiotic treated (week 4)

NCBI Quality ControlLinks
Actinomycetota
Bifidobacteriaceae
Bifidobacterium
Lactobacillus

Revision editor(s): Mmarin

Experiment 2


Reviewed Marked as Reviewed by Chloe on 2021/11/18

Curated date: 2021/10/07

Curator: Mmarin

Revision editor(s): WikiWorks, LGeistlinger, Mmarin, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Untreated controls (week 8)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Antibiotic treated (week 8)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Received parenteral antibiotic treatment with a combination of ampicillin and gentamicin within 48 hours of birth

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

Reviewed Marked as Reviewed by Chloe on 2021/11/18

Curated date: 2021/10/07

Curator: Mmarin

Revision editor(s): Mmarin

Source: Figure 1, Figure 2, Figure 3

Description: Figure 1: Microbial distributions at the phylum level in the samples from treated and control infants at week 4 and week 8. Figure 2: Microbial distributions at the family level in the samples from treated and control infants at week 4 and week 8. Figure 3: Microbial distributions at the genus level in the samples from treated and control infants at week 4 and week 8.

Statistically significant differences between treated infants and controls at week 8 are indicated by asterisks. Percentages are based on proportions of assignable tags.

Abundance in Group 1: increased abundance in Antibiotic treated (week 8)

NCBI Quality ControlLinks
Enterobacteriaceae
Pseudomonadota
unclassified Enterobacteriaceae

Revision editor(s): Mmarin

Experiment 3


Reviewed Marked as Reviewed by Chloe on 2021/11/18

Curated date: 2021/10/07

Curator: Mmarin

Revision editor(s): WikiWorks, LGeistlinger, Mmarin, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Week 4 (treated)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Week 8 (treated)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Had received parenteral antibiotic treatment with a combination of ampicillin and gentamicin within 48 hours of birth

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Chloe on 2021/11/18

Curated date: 2021/10/07

Curator: Mmarin

Revision editor(s): Mmarin

Source: Figure 1, Figure 2, Figure 3

Description: Figure 1: Microbial distributions at the phylum level in the samples from treated and control infants at week 4 and week 8. Figure 2: Microbial distributions at the family level in the samples from treated and control infants at week 4 and week 8. Figure 3: Microbial distributions at the genus level in the samples from treated and control infants at week 4 and week 8.

A statistically significant difference between treated infants at week 4 and week 8 (i.e., the recovery of the treated infants) is indicated by a diamond. Percentages are based on proportions of assignable tags.

Abundance in Group 1: increased abundance in Week 8 (treated)

NCBI Quality ControlLinks
Actinomycetota
Bifidobacteriaceae
Bifidobacterium

Revision editor(s): Mmarin

Signature 2

Reviewed Marked as Reviewed by Chloe on 2021/11/18

Curated date: 2021/10/07

Curator: Mmarin

Revision editor(s): Mmarin

Source: Figure 1, Figure 2, Figure 3

Description: Figure 1: Microbial distributions at the phylum level in the samples from treated and control infants at week 4 and week 8. Figure 2: Microbial distributions at the family level in the samples from treated and control infants at week 4 and week 8. Figure 3: Microbial distributions at the genus level in the samples from treated and control infants at week 4 and week 8.

A statistically significant difference between treated infants at week 4 and week 8 (i.e., the recovery of the treated infants) is indicated by a diamond. Percentages are based on proportions of assignable tags.

Abundance in Group 1: decreased abundance in Week 8 (treated)

NCBI Quality ControlLinks
Enterobacteriaceae
Peptostreptococcaceae
Pseudomonadota
unclassified Enterobacteriaceae

Revision editor(s): Mmarin