Antibiotic resistance potential of the healthy preterm infant gut microbiome

Rose, Graham; Shaw, Alexander; Sim, Kathleen; Wooldridge, David; Li, Mingshi; Gharbia, Saheer E.; Misra, Raju; Kroll, J. Simon

doi:10.7717/peerj.2928

Cited by 38 publications

(41 citation statements)

References 48 publications

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“…Our results indicate that prolonged treatment with antibiotics or CPAP oxygen creates a hostile environment for C. perfringens in the preterm gut, reducing probability of carriage. C. perfringens may be particularly impacted by antibiotics due a rarity of multiple drug resistance genes [40] compared to other members of the neonatal gut microbiota [41]. A reduction in the abundance of C. perfringens in the preterm infant gut with antibiotic exposure has been observed in another cohort, although not reduced prevalence [16].…”

Section: Discussionmentioning

confidence: 91%

Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants

et al. 2020

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Background: Clostridium perfringens forms part of the human gut microbiota and has been associated with lifethreatening necrotising enterocolitis (NEC) in premature infants. Whether specific toxigenic strains are responsible is unknown, as is the extent of diversity of strains in healthy premature babies. We investigated the C. perfringens carrier status of premature infants in the neonatal intensive care unit, factors influence this status, and the toxic potential of the strains. Methods: C. perfringens was isolated by culture from faecal samples from 333 infants and their toxin gene profiles analysed by PCR. A survival analysis was used to identify factors affecting probability of carriage. Competitive growth experiments were used to explore the results of the survival analysis. Results: 29.4% of infants were colonized with C. perfringens before they left hospital. Three factors were inversely associated with probability of carriage: increased duration of maternal milk feeds, CPAP oxygen treatment and antibiotic treatment. C. perfringens grew poorly in breast milk and was significantly outperformed by Bifidobacterium infantis, whether grown together or separately. Toxin gene screening revealed that infants carried isolates positive for collagenase, perfringolysin O, beta 2, beta, becA/B, netB and enterotoxin toxin genes, yet none were observed to be associated with the development of NEC. Conclusions: Approximately a third of preterm infants are colonised 3 weeks after birth with toxin gene-carrying C. perfringens. We speculate that increased maternal breast milk, oxygen and antibiotic treatment creates an environment in the gut hostile to growth of C. perfringens. Whilst potentially toxigenic C. perfringens isolates were frequent, no toxin type was associated with NEC. Trial registration: clinicaltrials.gov NCT01102738, registered 13th April 2010.

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Section: Discussionmentioning

confidence: 91%

Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants

et al. 2020

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“…The differences in ARG profiles across body sites has significant implications for the characterisation and interpretation of resistome studies. Previous shotgun metagenomic studies have focused almost exclusively on the resistome from the human gut [2][3][4]6 . While the gut may be a diverse reservoir of ARGs, whether these genes are particularly prevalent or have the potential for expression sufficient to drive resistant infections at other body sites is not clear 41 .…”

Section: Comparisons Between Oral and Gut Resistomes Reveal Differencmentioning

confidence: 99%

Abundance and diversity of resistomes differ between healthy human oral cavities and gut

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Witherden

Lee

et al. 2019

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The global threat of the "antimicrobial resistance apocalypse" that has arisen in recent years has driven the use of high-throughput sequencing techniques to monitor the profile of resistance genes, known as the "resistome", in microbial populations. The human oral cavity contains a poorly explored reservoir of these genes, and little is known about their abundance and diversity, or how their profile compares with antimicrobial resistance genes in the gut. Here we analyse the resistome profiles of 788 oral cavities worldwide and compare these profiles with paired stool samples from shotgun metagenomic data. We find country and body site-specific differences in the prevalence of antimicrobial resistance genes, classes and mechanisms in oral and stool samples. However, the 1 1 abundance of these antimicrobial resistance classes do not correlate with antibiotic prescription rates. A greater similarity was found in interpersonal resistomes between the same body sites than intrapersonal resistomes across different body sites. Between individuals, the oral cavity contains the highest and lowest abundances of specific antimicrobial resistance genes, but a lower diversity of resistance genes compared to the gut, which is likely influenced by differences in microbial composition and exposure to antimicrobial selection pressures. Co-occurrence analysis shows contrasting ARG-species associations between saliva and stool samples. This is the first study to date that characterises the oral cavity resistome worldwide, identifying its distinctive signatures compared to the gut.Maintenance and persistence of antimicrobial resistance is likely to vary across different body sites. Thus, we highlight the importance of characterising the resistome across body sites to uncover the antimicrobial resistance potential in the human body.

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“…High-throughput next-generation sequencing technologies are beginning to be used as tools for screening ARGs for potential surveillance of antimicrobial resistance worldwide. Shotgun metagenomic data mapped against dedicated ARG reference databases are providing a wealth of insight into the resistomes of human [2][3][4][5][6][7] and animal guts 8,9 , as well as the wider environment [10][11][12][13] . However, no large studies have, to date, attempted to characterise the resistome profiles of the human oral cavity.…”

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confidence: 99%

Abundance and diversity of resistomes differ between healthy human oral cavities and gut

et al. 2020

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The global threat of antimicrobial resistance has driven the use of high-throughput sequencing techniques to monitor the profile of resistance genes, known as the resistome, in microbial populations. The human oral cavity contains a poorly explored reservoir of these genes. Here we analyse and compare the resistome profiles of 788 oral cavities worldwide with paired stool metagenomes. We find country and body site-specific differences in the prevalence of antimicrobial resistance genes, classes and mechanisms in oral and stool samples. Within individuals, the highest abundances of antimicrobial resistance genes are found in the oral cavity, but the oral cavity contains a lower diversity of resistance genes compared to the gut. Additionally, co-occurrence analysis shows contrasting ARG-species associations between saliva and stool samples. Maintenance and persistence of antimicrobial resistance is likely to vary across different body sites. Thus, we highlight the importance of characterising the resistome across body sites to uncover the antimicrobial resistance potential in the human body.

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Antibiotic resistance potential of the healthy preterm infant gut microbiome

Cited by 38 publications

References 48 publications

Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants

Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants

Abundance and diversity of resistomes differ between healthy human oral cavities and gut

Abundance and diversity of resistomes differ between healthy human oral cavities and gut

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