Graduation Date

Spring 5-6-2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Dr. Ann Anderson-Berry

Second Advisor

Dr. Corrine Hanson

Third Advisor

Dr. Sathish Kumar Natarajan

Fourth Advisor

Dr. Melissa Thoene

Abstract

The gastrointestinal microbiome in preterm infants bears significant influence on optimal outcomes – dysbiosis is shown to substantially increase the risk of the life-threatening necrotizing enterocolitis, whereas optimal microbiome composition improves nutrient digestion and immune function. Iron is a vital nutrient especially during the perinatal window of rapid hemoglobin production, tissue growth, and foundational neurological development. However, excess colonic iron exhibits potent oxidation capacity and alters the competitive environment of microbes – potentially facilitating the proliferation of pathological bacterial strains in the gut. Of note, breastfed preterm infants routinely receive iron fortification starting at 14 days of life and are highly vulnerable to morbidities associated with gastrointestinal dysbiosis. Therefore, we set out to determine if routine iron fortification after two weeks of life shifted the preterm infant gut microbiome towards pathologic bacterial strains and assessed secondary measures of gastrointestinal inflammation. After IRB approval, we enrolled 14 infants bornfirst, second, and fourth week of life to assess gut microbiome composition at each timepoint. We observed no significant difference in phyla relative abundance nor key genera relative abundance in pre- and post-iron specimens. Gestational age at birth approached a significant correlation with Bifidobacteria relative abundance, and similarly Bifidobacteria relative abundance was higher among vaginally-delivered infants – though this difference only approached significance. Fecal calprotectin did not differ between pre- and post-iron specimens, nor did calprotectin correlate with relative abundance of any phyla or genera assessed. We observed notable seasonal shifts in infant microbiome composition, with infants delivered in Winter exhibiting significantly higher abundance of beneficial strains (Actinobacteria, Firmicutes) and Spring-born infants having higher proliferation of pathologic Proteobacteria (though only approaching significance). Though no obvious indication of iron-induced dysbiosis was observed in this unique study in the setting of prematurity, further investigation in a larger sample size is warranted to fully understand the impact of excess colonic iron on the gastrointestinal milieu.

Comments

2023 Copyright, the authors

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