Background: An urgent need exists for evidence-based dietary guidance early in life, particularly regarding protein intake. However, a significant knowledge gap exists in the effects of protein-rich foods on growth and development during early complementary feeding.Methods: This is a randomized controlled trial of infant growth and gut health (primary outcomes). We directly compare the effects of dietary patterns with common protein-rich foods (meat, dairy, plant) on infant growth trajectories and gut microbiota development (monthly assessments) during early complementary feeding in both breast- and formula-fed infants. Five-month-old infants (up to n = 300) are randomized to a meat-, dairy-, plant-based complementary diet or a reference group (standard of care) from 5 to 12 months of age, with a 24-month follow-up assessment. Infants are matched for sex, mode of delivery and mode of feeding using stratified randomization. Growth assessments include length, weight, head circumference and body composition. Gut microbiota assessments include both 16S rRNA profiling and metagenomics sequencing. The primary analyses will evaluate the longitudinal effects of the different diets on both anthropometric measures and gut microbiota. The secondary analysis will evaluate the potential associations between gut microbiota and infant growth.Discussion: Findings are expected to have significant scientific and health implications for identifying beneficial gut microbial changes and dietary patterns and for informing dietary interventions to prevent the risk of overweight and later obesity, and promote optimal health.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT05012930.
Background: Research is limited in evaluating the mechanisms responsible for infant growth in response to different protein-rich foods; Methods: Targeted and untargeted metabolomics analysis were conducted on serum samples collected from an infant controlled-feeding trial that participants consumed a meat- vs. dairy-based complementary diet from 5 to 12 months of age, and followed up at 24 months. Results: Isoleucine, valine, phenylalanine increased and threonine decreased over time among all participants; Although none of the individual essential amino acids had a significant impact on changes in growth Z scores from 5 to 12 months, principal component heavily weighted by BCAAs (leucine, isoleucine, valine) and phenylalanine had a positive association with changes in length-for-age Z score from 5 to 12 months. Concentrations of acylcarnitine-C4, acylcarnitine-C5 and acylcarnitine-C5:1 significantly increased over time with the dietary intervention, but none of the acylcarnitines were associated with infant growth Z scores. Quantitative trimethylamine N-oxide increased in the meat group from 5 to 12 months; Conclusions: Our findings suggest that increasing total protein intake by providing protein-rich complementary foods was associated with increased concentrations of certain essential amino acids and short-chain acyl-carnitines. The sources of protein-rich foods (e.g., meat vs. dairy) did not appear to differentially impact serum metabolites, and comprehensive mechanistic investigations are needed to identify other contributors or mediators of the diet-induced infant growth trajectories.
ObjectiveThis project aimed to evaluate the impact of meat- vs. dairy-based complementary foods on gut microbiota and whether it relates to growth.DesignFull-term, formula-fed infants were recruited from the metro Denver area (Colorado, US) and randomized to a meat- or dairy-based complementary diet from 5 to 12 months of age. Infant’s length and weight were measured, and stool samples were collected at 5, 10, and 12 months for 16S rRNA gene sequencing and short-chain fatty acids (SCFAs) quantification.ResultsSixty-four infants completed the dietary intervention (n = 32/group). Weight-for-age Z (WAZ) scores increased in both groups and length-for-age Z scores (LAZ) increased in the meat group only, which led to a significant group-by-time interaction (P = 0.02) of weight-for-length Z (WLZ) score. Microbiota composition (Beta-diversity) differed between groups at 12 months (weighted PERMANOVA P = 0.01) and had a group-by-time interaction of P = 0.09. Microbial community richness (Chao1) increased in the meat group only. Genus Akkermansia had a significant group-by-time interaction and increased in the dairy group and decreased in the meat group. A significant fold change of butyric acid from 5 to 12 months was found in the meat group (+1.75, P = 0.011) but not in the dairy group. Regression analysis showed that Chao1 had a negative association with WLZ and WAZ. Several genera also had significant associations with all growth Z scores.ConclusionComplementary feeding not only impacts infant growth but also affects gut microbiota maturation. Complementary food choices can affect both the gut microbiota diversity and structures and these changes in gut microbiota are associated with infant growth.
Objectives Growth and shifts of gut microbiota during infancy are greatly influenced by diet. Our objective is to both compare and characterize the gut microbiota and growth status according to feeding type in healthy U.S. infants. Methods Infants (4–5 months old) who were either exclusively breastfed or exclusively formula-fed infants were recruited from the metro Denver area. Stool samples along with the length and weight measurements, were collected from these infants, and fecal 16S rRNA gene-based profiling was conducted. Alpha diversity indices measured for the gut microbiota were tested using the Mann-Whitney statistic. Differences in microbiota composition (beta-diversity) were assessed by permutational ANOVA, using Aitchison dissimilarity scores. Individual taxa differing between groups were identified using the ANOVA-like Differential Expression tool (ALDEx2) to centered-log ratio transformed count data. Associations between gut microbial taxa and anthropometric Z scores were assessed by Spearman's rank correlation test. Length- and weight-for-age z-scores, and weight/length z-scores (LAZ, WAZ, WLZ) were assessed. Results 115 infants (breastfed n = 54; formula-fed n = 61) between the ages of 4 and 5 months were studies. Formula-fed infants had higher WAZ and WLZ than breastfed infants (p < 0.05). Although not statistically significant, LAZ was also higher in formula-fed compared to breastfed infants. (p = 0.14). Significant differences were observed in both the alpha and beta diversity and composition of fecal microbiota between breastfed and formula-fed infants. The breastfed cohort had lower alpha diversity than the formula-fed cohort. Bifidobacterium was the most abundant bacteria among all participants. Abundances of Bifidobacterium and Lactobacillus were greater in the breastfed group compared to the formula-fed group. Formula-fed infants tended to have a higher relative abundance of the unclassified Ruminococcaceae, which was associated with a higher WAZ (p < 0.001) and LAZ (p < 0.01), while Lactobacillus was associated with a statistically higher WAZ (p < 0.05). Conclusions The gut microbiota differences by feeding mode may contribute to differences in growth between breastfed and formula-fed infants. Funding Sources NIDDK, AHA, NPB, NCBA.
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