Ecological Processes Shaping Microbiomes of Extremely Low Birthweight Infants

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.

A Scoping Review of the Oral Microbiome in Preterm Infants

“…One study reported an association with IVH, but only 15 infants were included in their analysis. 22 No specific ASVs were identified, though a larger sample size may help identify pathogens associated with the oral microbiome and IVH. 22 The gut-brain axis may be associated with neurodevelopmental outcomes in preterm infants as certain gram-negative bacteria, may alter immunologic responses which result in neuroinflammation, and thus, may worsen neurological outcomes.…”

“…25 Likewise, one study reported the oral microbiome was more similar to the gut 14 and one study found amplicon sequencing variants (ASVs) to be more similar in the oral cavity and gut in comparison to other body sites, indicating site similarity due to proximity and/or environmental factors. 22…”

“…Two studies evaluated whether oral microbiome composition was associated with infant health outcomes. 14,22 Zioutis et al 22 reported oral microbiome composition was significantly associated with intraventricular hemorrhage (IVH), but no associated ASVs were identified. Young et al 14 found no association between oral microbiome composition and either NEC or late-onset sepsis.…”

Lysogeny destabilizes computationally simulated microbiomes

“…Our study does not answer that question. We studied return times from single disturbances, but real systems are likely to experience repeated disturbances [52, 53]. These could be stochastic [53] or predictable over time (e.g., due to diurnal cycles or regulation by the host immune system) [52].…”

“…We studied return times from single disturbances, but real systems are likely to experience repeated disturbances [52, 53]. These could be stochastic [53] or predictable over time (e.g., due to diurnal cycles or regulation by the host immune system) [52]. In the presence of repeated disturbances, it is not clear whether faster return to mean densities or faster dampening of cycles will keep systems closer to their equilibria, and the answer may depend on the disturbance regime.…”