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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

Effect of PAT on growth.(a) Timeline of antibiotic pulses and dietary changes. (b) Scale weight of mice. (c) Growth rates in early-, mid-, and late-life expressed as percent difference from control. (d–h) Dual energy X-ray absorptiometry measurements. (d–f) Total, lean and fat mass; (g) bone mineral content (BMC) and (h) bone area. (i) Calculated total body mass-to-bone area ratio is represented as a fraction of control. *P<0.05, **P<0.01, ANOVA with Dunnett's post test. (c–h) Bars represent standard error of the mean. Number of mice: control, n=6; amoxicillin, n=6; tylosin, n=7 and mixture, n=8.
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f1: Effect of PAT on growth.(a) Timeline of antibiotic pulses and dietary changes. (b) Scale weight of mice. (c) Growth rates in early-, mid-, and late-life expressed as percent difference from control. (d–h) Dual energy X-ray absorptiometry measurements. (d–f) Total, lean and fat mass; (g) bone mineral content (BMC) and (h) bone area. (i) Calculated total body mass-to-bone area ratio is represented as a fraction of control. *P<0.05, **P<0.01, ANOVA with Dunnett's post test. (c–h) Bars represent standard error of the mean. Number of mice: control, n=6; amoxicillin, n=6; tylosin, n=7 and mixture, n=8.

Mentions: Female C57BL/6J mice received three short courses of therapeutic-dose amoxicillin, tylosin, alternating courses of either antibiotic (mixture) or no antibiotics (control) (Fig. 1a and Supplementary Fig. 1). To mimic early life use by human children, the PAT was completed shortly after weaning, and then mice received high-fat chow to enhance metabolic phenotypes13. After one pulse, all mouse groups had identical weights on day 21 (Fig. 1b), but early-life PAT significantly increased the cumulative weight gain from 3 to 6 weeks, an effect continuing through late life in tylosin mice (Fig. 1c and Supplementary Fig. 1b).


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)

Effect of PAT on growth.(a) Timeline of antibiotic pulses and dietary changes. (b) Scale weight of mice. (c) Growth rates in early-, mid-, and late-life expressed as percent difference from control. (d–h) Dual energy X-ray absorptiometry measurements. (d–f) Total, lean and fat mass; (g) bone mineral content (BMC) and (h) bone area. (i) Calculated total body mass-to-bone area ratio is represented as a fraction of control. *P<0.05, **P<0.01, ANOVA with Dunnett's post test. (c–h) Bars represent standard error of the mean. Number of mice: control, n=6; amoxicillin, n=6; tylosin, n=7 and mixture, n=8.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Effect of PAT on growth.(a) Timeline of antibiotic pulses and dietary changes. (b) Scale weight of mice. (c) Growth rates in early-, mid-, and late-life expressed as percent difference from control. (d–h) Dual energy X-ray absorptiometry measurements. (d–f) Total, lean and fat mass; (g) bone mineral content (BMC) and (h) bone area. (i) Calculated total body mass-to-bone area ratio is represented as a fraction of control. *P<0.05, **P<0.01, ANOVA with Dunnett's post test. (c–h) Bars represent standard error of the mean. Number of mice: control, n=6; amoxicillin, n=6; tylosin, n=7 and mixture, n=8.
Mentions: Female C57BL/6J mice received three short courses of therapeutic-dose amoxicillin, tylosin, alternating courses of either antibiotic (mixture) or no antibiotics (control) (Fig. 1a and Supplementary Fig. 1). To mimic early life use by human children, the PAT was completed shortly after weaning, and then mice received high-fat chow to enhance metabolic phenotypes13. After one pulse, all mouse groups had identical weights on day 21 (Fig. 1b), but early-life PAT significantly increased the cumulative weight gain from 3 to 6 weeks, an effect continuing through late life in tylosin mice (Fig. 1c and Supplementary Fig. 1b).

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