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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

Dynamics of disruption, recovery and response to HFD.(a) Community structure over time within the four clusters identified by Calinski analysis shown for mothers and for pups at selected representative time points: after the first, second and third antibiotic pulses and after starting HFD. (b) Cluster assignment by mouse and time point. a, antibiotic group; c, cage (bars indicate mice in the same cage); m, mouse. Time points 1–14 correspond to sequential samples (correlating with increasing day of life). (c) Microbiota transition map, circles and lines are scaled to represent number of mice in each cluster (circle) or transitioning (line) between clusters. (d,e), Body composition grouped by day 50 cluster type at ∼50 days of life (d) and at ∼135 days of life (e). *P<0.05, **P<0.01, ***P<0.001, ANOVA with Tukey-post test. C, control; A, amoxicillin; T, tylosin; M, mother.
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f5: Dynamics of disruption, recovery and response to HFD.(a) Community structure over time within the four clusters identified by Calinski analysis shown for mothers and for pups at selected representative time points: after the first, second and third antibiotic pulses and after starting HFD. (b) Cluster assignment by mouse and time point. a, antibiotic group; c, cage (bars indicate mice in the same cage); m, mouse. Time points 1–14 correspond to sequential samples (correlating with increasing day of life). (c) Microbiota transition map, circles and lines are scaled to represent number of mice in each cluster (circle) or transitioning (line) between clusters. (d,e), Body composition grouped by day 50 cluster type at ∼50 days of life (d) and at ∼135 days of life (e). *P<0.05, **P<0.01, ***P<0.001, ANOVA with Tukey-post test. C, control; A, amoxicillin; T, tylosin; M, mother.

Mentions: Grouping samples by composition facilitates characterization of microbiota perturbations. Following evidence that human microbiota may segregate into clusters20, we asked whether the PAT-induced microbial shifts could be similarly characterized, and found that four distinct groups best captured the taxonomic variation (Supplementary Fig. 6a). Offspring control microbiota stably clustered with the maternal samples initially (cluster 1), then shifted to a new community state (cluster 4) immediately following introduction of HFD (Fig. 5a). Amoxicillin samples showed mild disruptions for half of the mice after at least two pulses, but converged with controls in cluster 4 shortly after HFD introduction. In tylosin and mixture mice, one tylosin pulse immediately disrupted microbiota, shifting samples to cluster 2 (mildly altered state) or cluster 3 (markedly altered from control). All samples shifted to cluster 3 following at least two doses of tylosin. As with amoxicillin, the samples eventually converged in cluster 4 following HFD, but this recovery was delayed and followed a distinct trajectory (Fig. 5b,c). These community dynamics indicate that sequential antibiotic treatments were more disruptive than single antibiotic exposure, show that tylosin had greater effect on the gut microbiota than amoxicillin and confirm the strong effect of diet on the microbiota19.


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)

Dynamics of disruption, recovery and response to HFD.(a) Community structure over time within the four clusters identified by Calinski analysis shown for mothers and for pups at selected representative time points: after the first, second and third antibiotic pulses and after starting HFD. (b) Cluster assignment by mouse and time point. a, antibiotic group; c, cage (bars indicate mice in the same cage); m, mouse. Time points 1–14 correspond to sequential samples (correlating with increasing day of life). (c) Microbiota transition map, circles and lines are scaled to represent number of mice in each cluster (circle) or transitioning (line) between clusters. (d,e), Body composition grouped by day 50 cluster type at ∼50 days of life (d) and at ∼135 days of life (e). *P<0.05, **P<0.01, ***P<0.001, ANOVA with Tukey-post test. C, control; A, amoxicillin; T, tylosin; M, mother.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Dynamics of disruption, recovery and response to HFD.(a) Community structure over time within the four clusters identified by Calinski analysis shown for mothers and for pups at selected representative time points: after the first, second and third antibiotic pulses and after starting HFD. (b) Cluster assignment by mouse and time point. a, antibiotic group; c, cage (bars indicate mice in the same cage); m, mouse. Time points 1–14 correspond to sequential samples (correlating with increasing day of life). (c) Microbiota transition map, circles and lines are scaled to represent number of mice in each cluster (circle) or transitioning (line) between clusters. (d,e), Body composition grouped by day 50 cluster type at ∼50 days of life (d) and at ∼135 days of life (e). *P<0.05, **P<0.01, ***P<0.001, ANOVA with Tukey-post test. C, control; A, amoxicillin; T, tylosin; M, mother.
Mentions: Grouping samples by composition facilitates characterization of microbiota perturbations. Following evidence that human microbiota may segregate into clusters20, we asked whether the PAT-induced microbial shifts could be similarly characterized, and found that four distinct groups best captured the taxonomic variation (Supplementary Fig. 6a). Offspring control microbiota stably clustered with the maternal samples initially (cluster 1), then shifted to a new community state (cluster 4) immediately following introduction of HFD (Fig. 5a). Amoxicillin samples showed mild disruptions for half of the mice after at least two pulses, but converged with controls in cluster 4 shortly after HFD introduction. In tylosin and mixture mice, one tylosin pulse immediately disrupted microbiota, shifting samples to cluster 2 (mildly altered state) or cluster 3 (markedly altered from control). All samples shifted to cluster 3 following at least two doses of tylosin. As with amoxicillin, the samples eventually converged in cluster 4 following HFD, but this recovery was delayed and followed a distinct trajectory (Fig. 5b,c). These community dynamics indicate that sequential antibiotic treatments were more disruptive than single antibiotic exposure, show that tylosin had greater effect on the gut microbiota than amoxicillin and confirm the strong effect of diet on the microbiota19.

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