Abstract

The human microbiome has been implicated in affecting health outcomes in premature infants, but the ecological processes governing early life microbiome assembly remain poorly understood. Here, we investigated microbial community assembly and dynamics in extremely low birth weight infants (ELBWI) over the first 2 weeks of life. We profiled the gut, oral cavity and skin microbiomes over time using 16S rRNA gene amplicon sequencing and evaluated the ecological forces shaping these microbiomes. Though microbiomes at all three body sites were characterized by compositional instability over time and had low body-site specificity (PERMANOVA, r2 = 0.09, p = 0.001), they could nonetheless be clustered into four discrete community states. Despite the volatility of these communities, deterministic assembly processes were detectable in this period of initial microbial colonization. To further explore these deterministic dynamics, we developed a probabilistic approach in which we modeled microbiome state transitions in each ELBWI as a Markov process, or a “memoryless” shift, from one community state to another. This analysis revealed that microbiomes from different body sites had distinctive dynamics as well as characteristic equilibrium frequencies. Time-resolved microbiome sampling of premature infants may help to refine and inform clinical practices. Additionally, this work provides an analysis framework for microbial community dynamics based on Markov modeling that can facilitate new insights, not only into neonatal microbiomes but also other human-associated or environmental microbiomes.

Highlights

  • Preterm birth remains one of the major risk factors for acute as well as long-term adverse health outcomes

  • We found that very abundant amplicon sequence variant (ASV) are likely to be present in all sampled sites from the same patient, which is consistent with the neutral theory of community assembly (Volkov et al, 2003)

  • In order to better understand the implications of these community state transitions, we evaluated the long-term consequences of these dynamics by calculating their steady-state probabilities using Markov chain theory

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Summary

Introduction

Preterm birth remains one of the major risk factors for acute as well as long-term adverse health outcomes. Afonso and Blot, 2017), bronchopulmonary dysplasia (BPD) (Thekkeveedu et al, 2017), retinopathy of prematurity (ROP) (Quimson, 2015) and intraventricular hemorrhage (IVH) (Poryo et al, 2018). These complications are an acute risk, but can lead to lasting neurodevelopmental impairment (Stoll et al, 2004). Microbial colonization plays a key role in the maturation and function of the immune system (Geva-Zatorsky et al, 2017) This is important for extremely preterm infants, as they are frequently exposed to invasive procedures such as catheterization, intubation and assisted ventilation, which are potent sources of nosocomial infections during intensive care (Ramasethu, 2017)

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