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Title:Dietary factors and early life development of the gut microbiota of preterm infants during hospitalization in the neonatal intensive care unit
Author(s):Aguilar Lopez, Miriam
Director of Research:Donovan, Sharon M
Doctoral Committee Chair(s):Swanson, Kelly
Doctoral Committee Member(s):Holscher, Hannah D; Teran-Garcia, Margarita
Department / Program:Nutritional Sciences
Discipline:Nutritional Sciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
gut microbiota
human milk
Abstract:In the United States, by 2018, 10% of the infants were born preterm (PT; <37 wks of gestation), with some as early as 23-24 weeks of gestation. Infants born PT are at higher risk of having short- and long-term complications. One of the most pressing challenges is how to feed these infants given their immature digestive and absorptive capacity and high nutrients needs. Furthermore, the gut microbiota of these infants has higher abundances of pathogenic bacteria and lower abundance of commensal bacteria. One of the major drivers of the gut microbiota is diet. Preterm infants can be fed different types of milk and milk fortifiers during their hospitalization period, which can influence the microbiota composition in different ways. Human milk is recommended compared to PT formula; however, it is not nutritionally adequate to meet the needs of infants. Thus, human milk is fortified with either a human milk- (HMF) or bovine milk-based fortifier (BMF). Furthermore, very few studies have investigated the effect of milk fortifiers on the gut microbiota of PT infants. This is significant given that human milk has to be fortified when fed to PT infants. In addition to diet, gut microbial colonization is known to be a multifactorial process, where different factors including genetics, environment, and other perinatal exposures play a role. Given the significant association between the gut microbiota and health, the overall goal of this dissertation research was to investigate how human milk in combination with either a HMF or a BMF milk fortifiers modulates gut microbial structure and function of hospitalized PT infants compared to PT formula consumption. Also, this dissertation analyzed how the gut bacterial characteristics are influenced by perinatal exposures, including the neonatal intensive care unit (NICU) environment, host genetics, and iron status. The central hypothesis was that the exposure to human milk or PT formula, with or without the addition of milk fortifiers during the NICU hospitalization will influence the structure and functional potential of the gut microbiota after birth. To test this hypothesis, four aims were undertaken: 1) Determine the characteristics of the gut microbiota of PT infants during hospitalization in the NICU in relation to dietary factors; 2) Examine the PT infant gut microbiota from multiplets and singletons admitted to two different NICUs after birth; 3) Evaluate the dynamics of iron status and its association with feeding type and gut microbial composition of PT infants hospitalized in the NICU; and, 4) Determine the effect of different feeding types on the functional potential of the gut microbiome of PT infants hospitalized in the NICU. Results of this dissertation were based on a longitudinal study of PT infants enrolled after birth and followed during the hospitalization period in the NICU. During this period, clinical data and feeding information was retrieved from the medical records. Stool samples were collected for each infant in weekly or bi-weekly basis. Additionally, a NICU from another hospital (Tampa General Hospital, FL) was also included as part of this study to determine the effect of different hospital settings. The V3-V4 region of the 16S rRNA gene were sequenced to determine the profile of the gut microbiota of PT infants. Analyses revealed that there were significant differences in the taxonomy of the gut microbiota of PT infants consuming human milk in combination with HMF or BMF fortifier. Moreover, the use of fortifiers, particularly BMF, was associated with a faster growth rate in PT infants consuming human milk. The gut microbiota of related PT infants (twins and triplets) significantly associated with alpha diversity and taxonomic composition. However, dietary and clinical factors such as BMF supplementation and weight seemed to significantly modify the gut microbiota regardless of infants being siblings or not, which suggest the strong effect of diet on modifications of the gut microbiota. Taxonomical differences were also found between the two different hospital settings. This highlights the effect of the environment in the gut microbiota colonization. Low iron status, which is a common feature of PT infants, was significantly associated with lower gestational age. When the relation between hemoglobin (Hb), feeding type and the gut microbiota characteristics were assessed, it was found that PT infants consuming human milk with a HMF, or infant formula had significantly lower Hb values than infants consuming human milk with BMF. There was a negative association between microbial richness and Hb status. Results from this study give an insight to the possible associations between Hb status and gut microbial composition, as well as the important effect of diet on iron status in PT infants. Lastly, the functional profile of the gut microbiome of PT infants fed their mother’s own milk (MOM) or infant formula was investigated. There were significant differences in metabolic pathways related to carbohydrate and fatty acid degradation, as well as in pathways for energy production. Taxonomically, the abundance of Bifidobacterium was higher in infants consuming MOM, compared to infants consuming infant formula. Particularly, Bifidobacterium longum had enriched metabolic pathways in the microbiome of infants consuming MOM. Overall, these findings suggest that milk fortifiers may play a greater role than human milk or infant formula in the colonization pattern of the gut microbiota of PT infants. The present study opens the door for future research aiming to develop targeted dietary strategies based on the use of HMF or BMF fortification in PT infants. Furthermore, clinical trials are needed to assess the differences in the gut microbial colonization of PT infants fed HMF or BMF. Additionally, more longitudinal studies are necessary to explore the long-term effects of the gut microbiota characteristics based on the feeding type after birth and how the gut microbiota could relate to the infant’s health status at a later life stage.
Issue Date:2021-07-12
Rights Information:Copyright 2021 Miriam Aguilar Lopez
Date Available in IDEALS:2022-01-12
Date Deposited:2021-08

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