Metagenomics analysis of the neonatal intestinal resistome

Leo, Stefano; Cetiner, Omer Faruk; Pittet, Laure F; Messina, Nicole L.; Jakob, William; Falquet, Laurent; Curtis, Nigel; Zimmermann, Petra

doi:10.3389/fped.2023.1169651

Cited by 3 publications

(1 citation statement)

References 58 publications

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“…In addition, the majority (70%) of ARGs found in the infant gut at one month were associated with predominance of nonbifidobacteria species, in particular E. coli. The presence of antibiotic resistance in the newborn gut has been reported in previous studies 35,36,56 , with indications of resistance transmission from the maternal gut to the infant gut via mobile genetic elements 57 . Our results show a significant overlap between the resistome of infants and that of their mother's milk, and that this overlap was particularly pronounced when evidence of strain sharing was found.…”

Section: Discussionmentioning

confidence: 57%

Assembly, stability, and dynamics of the infant gut microbiome are linked to bacterial strains and functions in mother’s milk

Allert,

Ferretti,

Johnson

et al. 2024

Preprint

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The establishment of the gut microbiome in early life is critical for healthy infant development. Although human milk is recommended as the sole source of nutrition for the human infant, little is known about how variation in milk composition, and especially the milk microbiome, shapes the microbial communities in the infant gut. Here, we quantified the similarity between the maternal milk and the infant gut microbiome using 507 metagenomic samples collected from 195 mother-infant pairs at one, three, and six months postpartum. We found that the microbial taxonomic overlap between milk and the infant gut was driven by bifidobacteria, in particular byB. longum. Infant stool samples dominated byB. longumalso showed higher temporal stability compared to samples dominated by other species. We identified two instances of strain sharing between maternal milk and the infant gut, one involving a commensal (B. longum) and one a pathobiont (K. pneumoniae). In addition, strain sharing between unrelated infants was higher among infants born at the same hospital compared to infants born in different hospitals, suggesting a potential role of the hospital environment in shaping the infant gut microbiome composition. The infant gut microbiome at one month compared to six months of age was enriched in metabolic pathways associated with de-novo molecule biosynthesis, suggesting that early colonisers might be more versatile and metabolically independent compared to later colonizers. Lastly, we found a significant overlap in antimicrobial resistance genes carriage between the mother's milk and their infant's gut microbiome. Taken together, our results suggest that the human milk microbiome has an important role in the assembly, composition, and stability of the infant gut microbiome.

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Section: Discussionmentioning

confidence: 57%

Assembly, stability, and dynamics of the infant gut microbiome are linked to bacterial strains and functions in mother’s milk

Allert,

Ferretti,

Johnson

et al. 2024

Preprint

View full text Add to dashboard Cite

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A cohort study in family triads: impact of gut microbiota composition and early life exposures on intestinal resistome during the first two years of life

Jokela,

Pärnänen,

Ponsero

et al. 2024

Gut Microbes

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Antibiotic resistance genes (ARGs) are prevalent in the infant gut microbiota and make up the intestinal resistome, representing a community ARG reservoir. This study focuses on the dynamics and persistence of ARGs in the early gut microbiota, and the effect of early exposures therein. We leveraged 2,328 stool metagenomes from 475 children in the HELMi cohort and the available parental samples to study the diversity, dynamics, and intra-familial sharing of the resistome during the first two years of life. We found higher within-family similarity of the gut resistome composition and ARG load in infant-mother pairs, and between spouses, but not in father-infant pairs. Early gut microbiota composition and development correlated with the ARG load; Bacteroides correlated positively and Bifidobacterium negatively with the load, reflecting the typical resistance levels in these taxa. Caesarean delivered infants harbored lower ARG loads, partly reflecting the scarcity of Bacteroides compared to vaginally delivered. Exposure to intrapartum or post-natal antibiotics showed only modest associations with the ARG load and composition, mainly before 12 months. Our results indicate that the resistome is strongly driven by the normal development of the microbiota in early life, and suggest importance of longer evolution of ARGs over effects of recent antibiotic exposure.

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Increased antibiotic resistance in preterm neonates under early antibiotic use

Ojeda,

Akinsuyi,

McKinley

et al. 2024

mSphere

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The standard use of antibiotics in newborns to empirically treat early-onset sepsis can adversely affect the neonatal gut microbiome, with potential long-term health impacts. Research into the escalating issue of antimicrobial resistance in preterm infants and antibiotic practices in neonatal intensive care units is limited. A deeper understanding of the effects of early antibiotic intervention on antibiotic resistance in preterm infants is crucial. This retrospective study employed metagenomic sequencing to evaluate antibiotic resistance genes (ARGs) in the meconium and subsequent stool samples of preterm infants enrolled in the Routine Early Antibiotic Use in Symptomatic Preterm Neonates study. Microbial metagenomics was conducted using a subset of fecal samples from 30 preterm infants for taxonomic profiling and ARG identification. All preterm infants exhibited ARGs, with 175 unique ARGs identified, predominantly associated with beta-lactam, tetracycline, and aminoglycoside resistance. Notably, 23% of ARGs was found in preterm infants without direct or intrapartum antibiotic exposure. Post-natal antibiotic exposure increases beta-lactam/tetracycline resistance while altering mechanisms that aid bacteria in withstanding antibiotic pressure. Microbial profiling revealed 774 bacterial species, with antibiotic-naive infants showing higher alpha diversity ( P = 0.005) in their microbiota and resistome compared with treated infants, suggesting a more complex ecosystem. High ARG prevalence in preterm infants was observed irrespective of direct antibiotic exposure and intensifies with age. Prolonged membrane ruptures and maternal antibiotic use during gestation and delivery are linked to alterations in the preterm infant resistome and microbiome, which are pivotal in shaping the ARG profiles in the neonatal gut. This study is registered with ClinicalTrials.gov as NCT02784821 . IMPORTANCE A high burden of antibiotic resistance in preterm infants poses significant challenges to neonatal health. The presence of antibiotic resistance genes, along with alterations in signaling, energy production, and metabolic mechanisms, complicates treatment strategies for preterm infants, heightening the risk of ineffective therapy and exacerbating outcomes for these vulnerable neonates. Despite not receiving direct antibiotic treatment, preterm infants exhibit a concerning prevalence of antibiotic-resistant bacteria. This underscores the complex interplay of broader influences, including maternal antibiotic exposure during and beyond pregnancy and gestational complications like prolonged membrane ruptures. Urgent action, including cautious antibiotic practices and enhanced antenatal care, is imperative to protect neonatal health and counter the escalating threat of antimicrobial resistance in this vulnerable population.

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Metagenomics analysis of the neonatal intestinal resistome

Cited by 3 publications

References 58 publications

Assembly, stability, and dynamics of the infant gut microbiome are linked to bacterial strains and functions in mother’s milk

Assembly, stability, and dynamics of the infant gut microbiome are linked to bacterial strains and functions in mother’s milk

A cohort study in family triads: impact of gut microbiota composition and early life exposures on intestinal resistome during the first two years of life

Increased antibiotic resistance in preterm neonates under early antibiotic use

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