BackgroundIdentification of factors that influence the neonatal gut microbiome is urgently needed to guide clinical practices that support growth of healthy preterm infants. Here, we examined the influence of nutrition and common practices on the gut microbiota and growth in a cohort of preterm infants.ResultsWith weekly gut microbiota samples spanning postmenstrual age (PMA) 24 to 46 weeks, we developed two models to test associations between the microbiota, nutrition and growth: a categorical model with three successive microbiota phases (P1, P2, and P3) and a model with two periods (early and late PMA) defined by microbiota composition and PMA, respectively. The more significant associations with phase led us to use a phase-based framework for the majority of our analyses. Phase transitions were characterized by rapid shifts in the microbiota, with transition out of P1 occurring nearly simultaneously with the change from meconium to normal stool. The rate of phase progression was positively associated with gestational age at birth, and delayed transition to a P3 microbiota was associated with growth failure. We found distinct bacterial metabolic functions in P1–3 and significant associations between nutrition, microbiota phase, and infant growth.ConclusionThe phase-dependent impact of nutrition on infant growth along with phase-specific metabolic functions suggests a pioneering potential for improving growth outcomes by tailoring nutrient intake to microbiota phase.Electronic supplementary materialThe online version of this article (10.1186/s40168-017-0377-0) contains supplementary material, which is available to authorized users.

BackgroundPostnatal development of early life microbiota influences immunity, metabolism, neurodevelopment, and infant health. Microbiome development occurs at multiple body sites, with distinct community compositions and functions. Associations between microbiota at multiple sites represent an unexplored influence on the infant microbiome. Here, we examined co-occurrence patterns of gut and respiratory microbiota in pre- and full-term infants over the first year of life, a period critical to neonatal development.ResultsGut and respiratory microbiota collected as longitudinal rectal, throat, and nasal samples from 38 pre-term and 44 full-term infants were first clustered into community state types (CSTs) on the basis of their compositional profiles. Multiple methods were used to relate the occurrence of CSTs to temporal microbiota development and measures of infant maturity, including gestational age (GA) at birth, week of life (WOL), and post-menstrual age (PMA). Manifestation of CSTs followed one of three patterns with respect to infant maturity: (1) chronological, with CST occurrence frequency solely a function of post-natal age (WOL), (2) idiosyncratic to maturity at birth, with the interval of CST occurrence dependent on infant post-natal age but the frequency of occurrence dependent on GA at birth, and (3) convergent, in which CSTs appear first in infants of greater maturity at birth, with occurrence frequency in pre-terms converging after a post-natal interval proportional to pre-maturity. The composition of CSTs was highly dissimilar between different body sites, but the CST of any one body site was highly predictive of the CSTs at other body sites. There were significant associations between the abundance of individual taxa at each body site and the CSTs of the other body sites, which persisted after stringent control for the non-linear effects of infant maturity. Canonical correlations exist between the microbiota composition at each pair of body sites, with the strongest correlations between proximal locations.ConclusionThese findings suggest that early microbiota is shaped by neonatal innate and adaptive developmental responses. Temporal progression of CST occurrence is influenced by infant maturity at birth and post-natal age. Significant associations of microbiota across body sites reveal distal connections and coordinated development of the infant microbial ecosystem.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0566-5) contains supplementary material, which is available to authorized users.

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Rationale Respiratory Syncytial Virus (RSV) is a leading cause of infant respiratory disease. Infant airway microbiota has been associated with respiratory disease risk and severity. The extent to which interactions between RSV and microbiota occur in the airway, and their impact on respiratory disease susceptibility and severity, are unknown. Objectives Characterize temporal associations between microbiota and RSV infection before, during, and after infants’ first respiratory illness. Methods 16S rRNA microbiota profiling of two infant cohorts in the first year of life: 1) a cross-sectional cohort of 89 RSV infected infants sampled during illness and 102 matched healthy controls, and 2) a matched longitudinal cohort of 12 infants who developed RSV infection and 12 who did not, sampled before, during, and after infection. Results We identified 12 taxa significantly associated with RSV infection. All 12 taxa were differentially abundant during infection, with 8 associated with disease severity. Nasal microbiota composition was more discriminative of healthy vs. infected than of disease severity. Conclusions Our findings elucidate the chronology of nasal microbiota dysbiosis and suggest an altered developmental trajectory associated with RSV infection. Microbial temporal dynamics reveal indicators of disease risk, correlates of illness and severity, and impact of RSV infection on microbiota composition.

27 28Background: Postnatal development of the microbiota in early life influences immunity, 29 metabolism, neurodevelopment and long-term infant health. Microbiome development occurs at 30 multiple body sites, each with distinct community compositions and functions. Associations 31 between microbiota at multiple sites represent an unexplored influence on the infant 32 microbiome. Here, we examined co-occurrence patterns of gut and respiratory microbiota in 33 pre-and full-term infants over the first year of life, a period critical to neonatal development and 34 risk of respiratory diseases. 35Results: Gut and respiratory microbiota collected as longitudinal rectal, throat and nasal 36 samples from 38 pre-term and 44 full-term infants were first clustered into community state 37 types (CSTs) on the basis of their composition. Multiple methods were used to relate the 38 occurrence of CSTs to several measures of infant maturity, including gestational age (GA) at 39 birth, week of life (WOL), and post menstrual age (PMA: equal to GA plus WOL). Manifestation 40 of CSTs followed one of three patterns with respect to infant maturity. First, chronological: 41 independent of infant maturity (GA) at birth, and strongly associated with post-natal age (WOL). 42 Second, idiosyncratic: primarily dependent on maturity (GA) at birth, with persistent differences 43 in CST occurrence between pre-and full-term infants through the first year of life. Third, 44 convergent: CSTs appear earlier in infants with greater maturity (GA) at birth, but after a 45 sufficient post-natal interval their occurrence in pre-term infants reaches parity with full-term 46 infants. The composition of CSTs was highly dissimilar between different body sites, but the 47 CST of any one body site was highly predictive of the CSTs at other body sites. There were 48 significant associations between the abundance of individual taxa at each body site and the 49