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Infant diet interventions: effects on the gastrointestinal microbiota
Date
2024
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Early diet shapes the function, composition, and diversity of bacterial communities of the gastrointestinal (gut) microbiome. In the context of the liquid diet of infancy, pre-, pro-, and synbiotics have been added to infant formula in an effort to more closely resemble human milk (HM) and its beneficial health properties. With the introduction of solid foods, commonly known as weaning, there is a paucity of literature regarding the impact of individual first foods on the gut microbiota. To this end, the objectives of this dissertation were to: 1) synthesize the literature surrounding the effects of prebiotics, probiotics, and synbiotics on the infant gut microbiome and other health outcomes; 2) evaluate the feasibility of a short-term vegetable feeding intervention on the infant gut microbiota and microRNA (miRNA) expression; 3) evaluate the effect of different first food types (i.e., grain, meat, vegetable, and fruit) on the gut microbiota of exclusively HM fed infants. ☐ To address the first objective, a systematic review was conducted to evaluate the efficacy of pre-, pro-, and synbiotics in infant formula; 32 randomized, controlled trials (RCTs) were identified for inclusion. Among them, the methods utilized to measure the gut microbiota varied (e.g., colony plating, fluorescence in situ hybridization, quantitative polymerase chain reaction, 16S sequencing). The totality of the evidence revealed a consistent trend wherein Bifidobacterium levels increased with supplementation of pre- and synbiotics, but not pro-biotics. Pro- and synbiotic supplementation generally led to increased levels of the bacterial strain supplemented in the formula. Fecal pH was lower and stool consistency was softer with the addition of certain pre- and synbiotics. Further studies of pro- and synbiotic supplementation, utilizing advanced sequencing methodologies for a more comprehensive analysis, are warranted. ☐ For the second objective, a feasibility study of healthy infants (n=11) was conducted to evaluate the relationships among vegetable consumption, gut microbiota, and miRNA expression. Infants were randomized to one of three arms: control, broccoli, or carrot. The control group maintained their liquid milk diet only, while the other groups consumed broccoli or carrot purees on days 1-3 in addition to their liquid milk diet. Stool samples were collected on days 0, 2, 4, and 6; genomic DNA and total RNA were extracted from stool samples to measure microbiota and miRNA outcomes. Compared to control, a trend towards a decrease in alpha diversity (Shannon index) was observed in the carrot group on days 2 and 4 and beta diversity (weighted Unifrac) differed between the carrot and broccoli groups. Streptococcus was increased at day 4 in the carrot compared to control group. For the miRNA, a decrease in expression of miR-217 and miR-590-5p was observed in both the broccoli and carrot groups compared to control, whereas an increase in eight and two different miRNAs were observed in carrot and broccoli groups, respectively. This study demonstrated the feasibility for short-term feeding interventions to investigate effects on and the relationship between microbial communities and miRNA expression. ☐ To address the third objective, a pilot RCT was conducted to investigate the effect of common first food types on the gut microbiome. Vaginally delivered, exclusively HM fed infants (n=41) that had not yet begun consuming solid foods were randomized to one of four groups: oatmeal cereal, beef, carrot, or prune, and were fed their randomized food 3x/day, 2oz each feeding, along with HM, for one week, followed by oatmeal cereal and HM for a second week. Stool samples were collected and diet intake was recorded. Genomic DNA was extracted from stool samples and the 16S gene (V1-V9 regions) was sequenced. This study is currently ongoing, with analyses conducted exclusively on participants completed to date (n=22). Focusing on the effects of time only, as expected, microbial diversity increased, and the relative abundance of bacterial taxa (genus level) also changed over time. Specific to the feeding intervention, preliminary results suggest that the introduction of meat resulted in a microbial profile characterized by lower alpha diversity in comparison to feeding cereal, fruit, or vegetables, and these latter three groups exhibited microbial profiles of equal alpha diversity. In these preliminary data, there were no differences by feeding group for beta diversity. Moreover, the feeding of prune appears to result in an increase in Klebsiella compared to feeding beef and carrot. Upon ceasing feeding of the first food, feeding oatmeal cereal further increased alpha diversity in infants previously fed meat as their first food. Beta diversity indices indicated a difference between the continuation of oatmeal cereal compared to the introduction of oatmeal cereal after prune. However, no differences were found in relative abundance. These analyses will be repeated, in a blinded manner, with the completion of the RCT to elucidate differential effects of first foods on the gut microbiome and contribute to the literature on optimal first foods. The value of this research may provide justification for the consideration of gut health in addition to nutritional requirements as part of infant feeding recommendations. ☐ In summary, variations in both liquid and complementary diet composition result in distinct impacts on the gut microbiota which in turn may influence host health. The results of this research establish the effects of short-term feeding interventions on gut microbial composition and emphasize the importance of the gut microbial profile as a consideration when formulating first food recommendations for infants.
Description
Keywords
Synbiotics, Gastrointestinal microbiome, Human milk, Bifidobacterium, Broccoli groups