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Stool microbiome, pH and short/branched chain fatty acids in infants receiving extensively hydrolyzed formula, amino acid formula, or human milk through two months of age.

ABSTRACT: BACKGROUND:Early infant feeding with intact or extensively hydrolyzed (EH) proteins or free amino acids (AA) may differentially affect intestinal microbiota composition and immune reactivity. This multicenter, double-blind, controlled, parallel-group, pilot study compared stool microbiota from Baseline (1-7?days of age) up to 60?days of age in healthy term infants who received mother's own milk (assigned to human milk [HM] reference group) (n?=?25) or were randomized to receive one of two infant formulas: AA-based (AAF; n?=?25) or EH cow's milk protein (EHF; n?=?28). Stool samples were collected (Baseline, Day 30, Day 60) and 16S rRNA genes were sequenced. Alpha (Shannon, Simpson, Chao1) and beta diversity (Bray Curtis) were analyzed. Relative taxonomic enrichment and fold changes were analyzed (Wilcoxon, DESEq2). Short/branched chain fatty acids (S/BCFA) were quantified by gas chromatography. Mean S/BCFA and pH were analyzed (repeated measures ANOVA). RESULTS:At baseline, alpha diversity measures were similar among all groups; however, both study formula groups were significantly higher versus the HM group by Day 60. Significant group differences in beta diversity at Day 60 were also detected, and study formula groups were compositionally more similar compared to HM. The relative abundance of Bifidobacterium increased over time and was significantly enriched at Day 60 in the HM group. In contrast, a significant increase in members of Firmicutes for study formula groups were detected at Day 60 along with butyrate-producing species in the EHF group. Stool pH was significantly higher in the AAF group at Days 30 and 60. Butyrate increased significantly from Baseline to Day 60 in the EHF group and was significantly higher in study formula groups vs HM at Day 60. Propionate was also significantly higher for EHF and AAF at Day 30 and AAF at Day 60 vs HM. Total and individual BCFA were higher for AAF and EHF groups vs HM through Day 60. CONCLUSIONS:Distinct patterns of early neonatal microbiome, pH, and microbial metabolites were demonstrated for infants receiving mother's own milk compared to AA-based or extensively hydrolyzed protein formula. Providing different sources of dietary protein early in life may influence gut microbiota and metabolites. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02500563 . Registered July 28, 2015.

SUBMITTER: Kok CR

PROVIDER: S-EPMC7650147 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Stool microbiome, pH and short/branched chain fatty acids in infants receiving extensively hydrolyzed formula, amino acid formula, or human milk through two months of age.

Kok Car Reen CR Brabec Bradford B Chichlowski Maciej M Harris Cheryl L CL Moore Nancy N Wampler Jennifer L JL Vanderhoof Jon J Rose Devin D Hutkins Robert R

BMC microbiology 20201109 1

<h4>Background</h4>Early infant feeding with intact or extensively hydrolyzed (EH) proteins or free amino acids (AA) may differentially affect intestinal microbiota composition and immune reactivity. This multicenter, double-blind, controlled, parallel-group, pilot study compared stool microbiota from Baseline (1-7 days of age) up to 60 days of age in healthy term infants who received mother's own milk (assigned to human milk [HM] reference group) (n = 25) or were randomized to receive one of tw ...[more]

PMID: 33167908

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Project description:BackgroundIn case of cow's milk allergy (CMA), pediatric guidelines recommend for children the use of extensively hydrolyzed formulas (eHFs) as elimination diet. According to the American Academy of Pediatrics, the hypoallergenicity of each specific eHF should be tested in subjects with CMA.MethodsA prospective, multicenter trial was performed to assess the tolerance/hypoallergenicity of a thickened casein-based eHF (eHCF, Allernova AR®, United Pharmaceuticals, France) in infants aged <12 months with CMA proven by a double-blind placebo-controlled food challenge. Its efficacy, measured through allergy symptoms monitoring and Cow's Milk-related Symptom Score (CoMiSS) calculation, and safety were evaluated during a 4-month feeding period. Growth z-scores were computed based on WHO anthropometric data.ResultsThirty infants (mean age: 4.8 ± 3.0 months) with CMA proven by a DBPCFC tolerated the eHCF during the 4-month study. The CoMiSS, crying and regurgitation scores significantly decreased by 4.2 ± 4.0, 0.9 ±1.2 and 0.7 ± 1.1 respectively, after 14 days of feeding (p < 0.001). The Scoring Atopic Dermatitis index, of 33.2 ± 14.8 at inclusion in 9 patients, significantly decreased by 15.5 ± 6.7 and 21.1 ± 11.2, after 14 and 45 days of feeding, respectively (p < 0.001). The percentage of infants having normal stool consistency (soft or formed stools) significantly improved from 66.7 % (20/30) at inclusion to 90.0 % (27/30) after 14 days of feeding (p = 0.020). The growth z-scores, negative at study inclusion, significantly improved over the 4-month study. No adverse event was related to the eHCF.ConclusionThe thickened eHCF was tolerated by more than 90 % of included allergic infants with 95 % confidence interval and can therefore be considered as hypoallergenic in accordance with current guidelines. The improvement of growth indices and absence of related adverse events confirmed its safety. Results of this trial back the use of the tested thickened eHCF as an efficient and safe alternative in children with CMA.Trial registrationClinicalTrials.gov, number NCT02351531 , registered on 27 January 2015.

Project description:Abstract Objectives The first year of life is a critical window for appropriate enteric microbiome development. Variations in infant diets have persistent effects on gut microbial ecology. Compared to intact protein formulas (IPF), partially hydrolyzed infant formulas (PHF) contain broken down milk proteins and may impact development of atopic conditions in high-risk infants. However, the effects of PHFs on the developing gut microbiome are not known. Methods This study was a secondary analysis of the GLOWING study (ClinicalTrials.gov NCT01131117). Infant stool samples were collected at 6 months of age and microbial composition was examined via 16S rRNA amplicon sequencing (V4 region) using standardized methods. Samples were grouped by primary feeding type: Exclusive breastfeeding (BF; n = 42), IPF (n = 17), or PHF (n = 12). We used linear models to examine the effects of feeding type adjusting for lifetime breastfeeding exposure at 6 mo. Group differences in α-diversity (richness and diversity) and relative abundances were assessed by ANOVA or t-test. Between-specimen diversity (β-diversity) was assessed using Bray − Curtis dissimilarities. Results Total breast milk exposure did not differ between PHF and IPF (mean 32.3% of feeds from human milk, p = 0.08). Analysis of α-diversity showed higher evenness (Shannon, Simpson) in IPF and higher richness (Chao1, Observed OTU) in PHF. However, these differences were no longer significant after adjusting for breastmilk exposure. β-diversity did not differ between groups. At the genus level compared to BF, infants fed IPF had higher abundance of Parabacteroides, while those fed PHF had higher Erwinia and Clostridium. Peptostreptococcaceae family was also increased in PHF fed infants. Compared to IPF, the PHF group had higher abundance of Clostridium genus, and Peptostreptococcaceae and Enterobacteriaceae families. Elevated Enterobacteriaceae and Clostridiales have previously been found in children with food allergies. Conclusions Our results suggest that partially hydrolyzed infant formulas may have modest impacts on the gut microbiome compared to intact protein formulas. Larger samples sizes are needed to fully characterize these differences and potential influence on long-term health. Funding Sources U.S. Department of Agriculture, NIDDK.

Dataset Information

Stool microbiome, pH and short/branched chain fatty acids in infants receiving extensively hydrolyzed formula, amino acid formula, or human milk through two months of age.

Publications

Stool microbiome, pH and short/branched chain fatty acids in infants receiving extensively hydrolyzed formula, amino acid formula, or human milk through two months of age.

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