RESUMEN
The acquisition and development of the infant microbiome are key to establishing a healthy host-microbiome symbiosis. The maternal microbial reservoir is thought to play a crucial role in this process. However, the source and transmission routes of the infant pioneering microbes are poorly understood. To address this, we longitudinally sampled the microbiome of 25 mother-infant pairs across multiple body sites from birth up to 4 months postpartum. Strain-level metagenomic profiling showed a rapid influx of microbes at birth followed by strong selection during the first few days of life. Maternal skin and vaginal strains colonize only transiently, and the infant continues to acquire microbes from distinct maternal sources after birth. Maternal gut strains proved more persistent in the infant gut and ecologically better adapted than those acquired from other sources. Together, these data describe the mother-to-infant microbiome transmission routes that are integral in the development of the infant microbiome.
Asunto(s)
ADN Bacteriano/genética , Microbioma Gastrointestinal/genética , Tracto Gastrointestinal/microbiología , Relaciones Madre-Hijo , Adulto , Heces/microbiología , Femenino , Humanos , Lactante , Estudios Longitudinales , Metagenómica , Persona de Mediana Edad , Boca/microbiología , Piel/microbiología , Factores de Tiempo , Vagina/microbiologíaRESUMEN
The gut microbiome becomes shaped in the first days of life and continues to increase its diversity during the first months. Links between the configuration of the infant gut microbiome and infant health are being shown, but a comprehensive strain-level assessment of microbes vertically transmitted from mother to infant is still missing. We collected fecal and breast milk samples from multiple mother-infant pairs during the first year of life and applied shotgun metagenomic sequencing followed by computational strain-level profiling. We observed that several specific strains, including those of Bifidobacterium bifidum, Coprococcus comes, and Ruminococcus bromii, were present in samples from the same mother-infant pair, while being clearly distinct from those carried by other pairs, which is indicative of vertical transmission. We further applied metatranscriptomics to study the in vivo gene expression of vertically transmitted microbes and found that transmitted strains of Bacteroides and Bifidobacterium species were transcriptionally active in the guts of both adult and infant. By combining longitudinal microbiome sampling and newly developed computational tools for strain-level microbiome analysis, we demonstrated that it is possible to track the vertical transmission of microbial strains from mother to infants and to characterize their transcriptional activity. Our work provides the foundation for larger-scale surveys to identify the routes of vertical microbial transmission and its influence on postinfancy microbiome development. IMPORTANCE Early infant exposure is important in the acquisition and ultimate development of a healthy infant microbiome. There is increasing support for the idea that the maternal microbial reservoir is a key route of microbial transmission, and yet much is inferred from the observation of shared species in mother and infant. The presence of common species, per se, does not necessarily equate to vertical transmission, as species exhibit considerable strain heterogeneity. It is therefore imperative to assess whether shared microbes belong to the same genetic variant (i.e., strain) to support the hypothesis of vertical transmission. Here we demonstrate the potential of shotgun metagenomics and strain-level profiling to identify vertical transmission events. Combining these data with metatranscriptomics, we show that it is possible not only to identify and track the fate of microbes in the early infant microbiome but also to investigate the actively transcribing members of the community. These approaches will ultimately provide important insights into the acquisition, development, and community dynamics of the infant microbiome.
RESUMEN
BACKGROUND: The correct establishment of the human gut microbiota represents a crucial development that commences at birth. Different hypotheses propose that the infant gut microbiota is derived from, among other sources, the mother's fecal/vaginal microbiota and human milk. RESULTS: The composition of bifidobacterial communities of 25 mother-infant pairs was investigated based on an internal transcribed spacer (ITS) approach, combined with cultivation-mediated and genomic analyses. We identified bifidobacterial strains/communities that are shared between mothers and their corresponding newborns. Notably, genomic analyses together with growth profiling assays revealed that bifidobacterial strains that had been isolated from human milk are genetically adapted to utilize human milk glycans. In addition, we identified particular bacteriophages specific of bifidobacterial species that are common in the viromes of mother and corresponding child. CONCLUSIONS: This study highlights the transmission of bifidobacterial communities from the mother to her child and implies human milk as a potential vehicle to facilitate this acquisition. Furthermore, these data represent the first example of maternal inheritance of bifidobacterial phages, also known as bifidophages in infants following a vertical transmission route.
Asunto(s)
Bacteriófagos/fisiología , Bifidobacterium/genética , Bifidobacterium/fisiología , Bifidobacterium/virología , Microbioma Gastrointestinal , Madres , Bacteriófagos/genética , Bacteriófagos/aislamiento & purificación , Bifidobacterium/aislamiento & purificación , Lactancia Materna , Heces/microbiología , Humanos , Lactante , Recién Nacido , Leche Humana/microbiología , Polisacáridos/metabolismo , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: S. Chiara hospital is the only neonatal intensive care unit (NICU) in the Province of Trento (Italy). It serves a population of about 460000 people with about 5000 infants per year, admitting the totality of the inborn and outborn VLBWI of the province. The aim of this work is to compare mortality, morbidity and neonatal treatment of the very low birth weight infants (VLBWI) of Trento area with those recorded in the Vermont Oxford Network (VON) during 2004. METHODS: In this retrospective analysis, the rates of complications and related treatments reported in VLBWI admitted in the S. Chiara NICU during the period 2000-2005 were compared with those recorded in the VON in 2004. The analysis included both the total populations and different weight groups. RESULTS: The frequency of inborn infants was significantly higher in Trento than in VON: 91% vs 84% (MH 8.56; p-value 0.003). The administration of prenatal steroids (82% vs 74%; MH 7.47 and p-value 0.006) and caesarean section were significantly more frequent in the Trento area than in VON. In Trento significantly more VLBWI with BW = 1000 grams were given surfactant prophylaxis compared with VON and significantly fewer VLBWI in every Trento weight group developed RDS (MH 18.55; p-value 0.00001). Overall rates of complications (CLD, PDA, NEC, IVH) were significantly lower than in the Vermont Oxford Network. In CLD and PDA the differences were marked also in infants weighting less than 1000 grams. Overall rates of PNX, PVL, severe grade of ROP and mortality were similar in the two populations. In Trento, significantly more infants were discharged on human milk than in VON, in both the overall population and in BW sub-groups. CONCLUSION: On the basis of this analysis, a less aggressive therapeutic strategy based on perinatal prevention in global management, such as that employed in Trento area, may be associated with an improvement in clinical outcomes in very low birth weight infants.