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Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment.

Nobel YR, Cox LM, Kirigin FF, Bokulich NA, Yamanishi S, Teitler I, Chung J, Sohn J, Barber CM, Goldfarb DS, Raju K, Abubucker S, Zhou Y, Ruiz VE, Li H, Mitreva M, Alekseyenko AV, Weinstock GM, Sodergren E, Blaser MJ - Nat Commun (2015)

Bottom Line: Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development.Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic.This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.

ABSTRACT
Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

No MeSH data available.


Related in: MedlinePlus

Selection for antibiotic resistance genes in the intestinal metagenome.Frequency of specified antibiotic resistance genes (a–f) that were detected in dams, controls, amoxicillin and tylosin mice, shown in relation to the total number of sequence reads for that sample is shown. Dotted lines, antibiotic pulses; pink, HFD.
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f7: Selection for antibiotic resistance genes in the intestinal metagenome.Frequency of specified antibiotic resistance genes (a–f) that were detected in dams, controls, amoxicillin and tylosin mice, shown in relation to the total number of sequence reads for that sample is shown. Dotted lines, antibiotic pulses; pink, HFD.

Mentions: Multiple classes of antibiotic resistance-associated genes were examined by mapping the metagenomic reads to the resistance gene database. Among genes related to macrolide resistance, four—acrA, acrB, ant3Ia and ant2Ia—were present at very low frequency (<10−7) among dams (Fig. 7a–d). However, all three mice in the tylosin group showed blooms of these genes to ∼10−4, as did one of the mice receiving amoxicillin. No controls showed a change in frequency of these genes. The same mouse receiving amoxicillin and the three tylosin-receiving mice all had blooms of ampC, a beta-lactamase gene (Fig. 7e). For 15 tetracycline genes (Fig. 7f) and for hundreds of other genes in the metagenome, there were no differences between mothers, controls and antibiotic-receiving mice, indicating a lack of selection for their resistances.


Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment.

Nobel YR, Cox LM, Kirigin FF, Bokulich NA, Yamanishi S, Teitler I, Chung J, Sohn J, Barber CM, Goldfarb DS, Raju K, Abubucker S, Zhou Y, Ruiz VE, Li H, Mitreva M, Alekseyenko AV, Weinstock GM, Sodergren E, Blaser MJ - Nat Commun (2015)

Selection for antibiotic resistance genes in the intestinal metagenome.Frequency of specified antibiotic resistance genes (a–f) that were detected in dams, controls, amoxicillin and tylosin mice, shown in relation to the total number of sequence reads for that sample is shown. Dotted lines, antibiotic pulses; pink, HFD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4491183&req=5

f7: Selection for antibiotic resistance genes in the intestinal metagenome.Frequency of specified antibiotic resistance genes (a–f) that were detected in dams, controls, amoxicillin and tylosin mice, shown in relation to the total number of sequence reads for that sample is shown. Dotted lines, antibiotic pulses; pink, HFD.
Mentions: Multiple classes of antibiotic resistance-associated genes were examined by mapping the metagenomic reads to the resistance gene database. Among genes related to macrolide resistance, four—acrA, acrB, ant3Ia and ant2Ia—were present at very low frequency (<10−7) among dams (Fig. 7a–d). However, all three mice in the tylosin group showed blooms of these genes to ∼10−4, as did one of the mice receiving amoxicillin. No controls showed a change in frequency of these genes. The same mouse receiving amoxicillin and the three tylosin-receiving mice all had blooms of ampC, a beta-lactamase gene (Fig. 7e). For 15 tetracycline genes (Fig. 7f) and for hundreds of other genes in the metagenome, there were no differences between mothers, controls and antibiotic-receiving mice, indicating a lack of selection for their resistances.

Bottom Line: Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development.Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic.This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.

ABSTRACT
Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

No MeSH data available.


Related in: MedlinePlus