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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

Ecological outcomes from early-life PAT and response to dietary intervention.(a) Experimental design and timing of microbiota samples. (b) α-diversity measured at a coverage depth of 3,000 sequences per sample. (c) Differentiating bacterial families immediately before and after introduction of HFD. Area-under-curve (AUC) with 95% confidence intervals (grey lines) for differentiating pre-HFD and post-HFD mice is plotted by treatment group in major families (>1% relative abundance in at least one mouse). Significantly predictive results (Mann–Whitney test) after false-discovery rate correction (q<0.05) are indicated by grey-filled circles.
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f3: Ecological outcomes from early-life PAT and response to dietary intervention.(a) Experimental design and timing of microbiota samples. (b) α-diversity measured at a coverage depth of 3,000 sequences per sample. (c) Differentiating bacterial families immediately before and after introduction of HFD. Area-under-curve (AUC) with 95% confidence intervals (grey lines) for differentiating pre-HFD and post-HFD mice is plotted by treatment group in major families (>1% relative abundance in at least one mouse). Significantly predictive results (Mann–Whitney test) after false-discovery rate correction (q<0.05) are indicated by grey-filled circles.

Mentions: Microbiota composition was surveyed by sequencing the 16S rRNA gene from serial PAT and control pup faecal pellets and from representative mothers (Fig. 3a), yielding 2,683,548 quality-filtered sequences with a mean±s.d. depth of 6,899±3,009 sequences per sample. The richness and Shannon Index remained relatively constant in control mice, with α-diversity similar to their mothers; however, PAT decreased both richness and Shannon evenness even after one antibiotic pulse, with immediate and sustained reductions in diversity more pronounced following tylosin exposure (Fig. 3b). While amoxicillin resulted in milder reductions, there was a progressive loss with each dose, indicating the importance of both class and number of courses. Although the PAT groups largely converged with control over time, differences never fully resolved.


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)

Ecological outcomes from early-life PAT and response to dietary intervention.(a) Experimental design and timing of microbiota samples. (b) α-diversity measured at a coverage depth of 3,000 sequences per sample. (c) Differentiating bacterial families immediately before and after introduction of HFD. Area-under-curve (AUC) with 95% confidence intervals (grey lines) for differentiating pre-HFD and post-HFD mice is plotted by treatment group in major families (>1% relative abundance in at least one mouse). Significantly predictive results (Mann–Whitney test) after false-discovery rate correction (q<0.05) are indicated by grey-filled circles.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Ecological outcomes from early-life PAT and response to dietary intervention.(a) Experimental design and timing of microbiota samples. (b) α-diversity measured at a coverage depth of 3,000 sequences per sample. (c) Differentiating bacterial families immediately before and after introduction of HFD. Area-under-curve (AUC) with 95% confidence intervals (grey lines) for differentiating pre-HFD and post-HFD mice is plotted by treatment group in major families (>1% relative abundance in at least one mouse). Significantly predictive results (Mann–Whitney test) after false-discovery rate correction (q<0.05) are indicated by grey-filled circles.
Mentions: Microbiota composition was surveyed by sequencing the 16S rRNA gene from serial PAT and control pup faecal pellets and from representative mothers (Fig. 3a), yielding 2,683,548 quality-filtered sequences with a mean±s.d. depth of 6,899±3,009 sequences per sample. The richness and Shannon Index remained relatively constant in control mice, with α-diversity similar to their mothers; however, PAT decreased both richness and Shannon evenness even after one antibiotic pulse, with immediate and sustained reductions in diversity more pronounced following tylosin exposure (Fig. 3b). While amoxicillin resulted in milder reductions, there was a progressive loss with each dose, indicating the importance of both class and number of courses. Although the PAT groups largely converged with control over time, differences never fully resolved.

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