Infant Metabolome Research Articles

Impact of two human milk oligosaccharides and lactose on the faecal microbiome of infants with probable cow's milk allergy.

Cow's milk protein allergy (CMPA) in infancy is associated with intestinal microbial dysbiosis, characterised by low Bifidobacteriaceae levels. The present study aimed to investigate the impact of two human milk oligosaccharides (HMO), lactose (L), and their combination on the faecal microbiome and metabolome of infants with CMPA. Stool samples of 12 term infants with probable CMPA (mean age 4.3 months) were analysed using a validated intestinal fermentation assay (SIFR® technology). For each substrate (i.e. HMO (2'-fucosyllactose [2'-FL] and lacto-N-neotetraose [LNnT]), L and HMO + L), taxonomic microbiome characterisation and untargeted metabolite profiling were performed at multiple timepoints. At baseline, the tested faecal microbiota overall displayed low abundances of Bifidobacteriaceae. Fermentation with either HMO or lactose significantly enriched Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium pseudocatenulatum and, for HMO + L, also Bifidobacterium bifidum. The increase in HMO-utilising bifidobacteria was associated with a significant rise in levels of short-chain fatty acids, aromatic lactic acids and N-acetylated amino acids, with additive effects being observed for HMO + L. The above data suggest that the combination of 2'-FL, LNnT and lactose helps to alleviate the previously reported CMPA-associated intestinal bacterial dysbiosis and induces the production of several beneficial metabolites. The clinical significance of these findings for infants with CMPA requires further investigation.

Urinary metabolome of infants with colic treated with Lactobacillus reuteri DSM 17938: a pilot randomized trial.

Lactobacillus reuteri DSM 17938 is the only probiotic recommended for treatment of colicky infants, but its mechanism of action is not clear. The study aim was to examine urinary metabolomic fingerprint of colicky breastfed infants before and after 1 month of orally administered Lactobacillus reuteri DSM 17938 or placebo. This randomized, blinded, placebo-controlled clinical trial was carried out with a well-documented probiotic. Thirty-two infants were enrolled, 16 in the probiotic group and 16 in the placebo group. Urine samples were collected from each subject before starting supplementation and at the end of the study period. Metabolomic profiles were obtained using a gas chromatography/mass spectrometry instrument. Subsequently, to compare groups before and after probiotic supplementation, univariate and multivariate statistical analysis were performed. In the L. reuteri treated group all metabolites for all class of nutrients (sugars, amino acids, carboxylic acids) resulted more abundant after the study period. The comparison with a control group (placebo treated), confirmed this effect on urines. The metabolomic analysis of urine samples from infants treated with L. reuteri DSM 17938 allowed to detect some interesting features related to the effect of this treatment on urinary metabolome. To validate the results, a test on a larger cohort is required.

Longitudinal dynamics of the gut microbiome and metabolome in peanut allergy development

Rising rates of peanut allergy (PA) motivate investigations of its development to inform prevention and therapy. Microbiota and the metabolites they produce shape food allergy risk. We sought to gain insight into gut microbiome and metabolome dynamics in the development of PA. We performed a longitudinal, integrative study of the gut microbiome and metabolome of infants with allergy risk factors but no PA from a multicenter cohort followed through mid-childhood. We performed 16S rRNA sequencing, short chain fatty acid measurements, and global metabolome profiling of fecal samples at infancy and at mid-childhood. In this longitudinal, multicenter sample (n= 122), 28.7% of infants developed PA by mid-childhood (mean age 9 years). Lower infant gut microbiome diversity was associated with PA development (P= .014). Temporal changes in the relative abundance of specific microbiota and gut metabolite levels significantly differed in children who developed PA. PA-bound children had different abundance trajectories of Clostridium sensu stricto 1 sp (false discovery rate (FDR)= 0.015) and Bifidobacterium sp (FDR= 0.033), with butyrate (FDR= 0.045) and isovalerate (FDR= 0.036) decreasing over time. Metabolites associated with PA development clustered within the histidine metabolism pathway. Positive correlations between microbiota, butyrate, and isovalerate and negative correlations with histamine marked the PA-free network. The temporal dynamics of the gut microbiome and metabolome in early childhood are distinct for children who develop PA. These findings inform our thinking on the mechanisms underlying and strategies for potentially preventing PA.

Protocol for a prospective cohort study exploring the gut microbiota of infants with congenital heart disease undergoing cardiopulmonary bypass (the GuMiBear study)

IntroductionThe gut microbiota develops from birth and matures significantly during the first 24 months of life, playing a major role in infant health and development. The composition of the gut...

Interstage Single Ventricle Heart Disease Infants Show Dysregulation in Multiple Metabolic Pathways: Targeted Metabolomics Analysis

BackgroundInfants with SVHD experience morbidity related to pulmonary vascular inadequacy. Metabolomic analysis involves a systems biology approach to identifying novel biomarkers and pathways in complex diseases. The metabolome of infants with SVHD is not well understood and no prior study has evaluated the relationship between serum metabolite patterns and pulmonary vascular readiness for staged SVHD palliation. ObjectivesThe purpose of this study was to evaluate the circulating metabolome of interstage infants with single ventricle heart disease (SVHD) and determine whether metabolite levels were associated with pulmonary vascular inadequacy. MethodsThis was a prospective cohort study of 52 infants with SVHD undergoing Stage 2 palliation and 48 healthy infants. Targeted metabolomic phenotyping (175 metabolites) was performed by tandem mass spectrometry on SVHD pre-Stage 2, post-Stage 2, and control serum samples. Clinical variables were extracted from the medical record. ResultsRandom forest analysis readily distinguished between cases and controls and preoperative and postoperative samples. Seventy-four of 175 metabolites differed between SVHD and controls. Twenty-seven of 39 metabolic pathways were altered including pentose phosphate and arginine metabolism. Seventy-one metabolites differed in SVHD patients between timepoints. Thirty-three of 39 pathways were altered postoperatively including arginine and tryptophan metabolism. We found trends toward increased preoperative methionine metabolites in patients with higher pulmonary vascular resistance and higher postoperative tryptophan metabolites in patients with greater postoperative hypoxemia. ConclusionsThe circulating metabolome of interstage SVHD infants differs significantly from controls and is further disrupted after Stage 2. Several metabolites showed trends toward association with adverse outcomes. Metabolic dysregulation may be an important factor in early SVHD pathobiology.

Abstract 13196: Inter-Stage Infants With Single Ventricle Heart Disease Show Prominent Dysregulation in Multiple Metabolic Pathways: A Targeted Metabolomics Analysis

Objectives: To evaluate the circulating metabolome of interstage infants with single ventricle heart disease (SVHD) and determine whether metabolite levels were associated with pulmonary vascular inadequacy. Background: Infants with SVHD experience morbidity related to pulmonary vascular inadequacy. Metabolomic analysis involves a systems biology approach to identifying novel biomarkers and pathways in complex diseases. The metabolome of infants with SVHD is not well understood and no prior study has evaluated the relationship between metabolite levels and pulmonary vascular readiness for staged SVHD palliation. Methods: Prospective cohort study of 52 infants with SVHD undergoing Stage 2 palliation and 48 healthy infants. Targeted metabolomic phenotyping (n=175 metabolites) performed by tandem mass spectrometry on SVHD pre-Stage 2, post-Stage 2, and control serum samples. Clinical variables were extracted from the medical record. Results: Random Forest analysis readily distinguished between cases and controls (Figure), and pre-op and post-op samples. Seventy-four of 175 metabolites differed between SVHD and controls. Twenty-seven of 39 metabolic pathways were altered including pentose phosphate and arginine metabolism. Seventy-one metabolites differed in SVHD patients between timepoints. Thirty-three of 39 pathways were altered post-operatively including arginine and tryptophan metabolism. We found trends towards increased pre-operative methionine metabolites in patients with higher pulmonary vascular resistance and higher post-operative tryptophan metabolites in patients with greater post-operative hypoxemia. Conclusions: The circulating metabolome of interstage SVHD infants differs significantly from controls and is further disrupted after Stage 2. Several metabolites showed promising trends towards association with adverse outcomes. Metabolic dysregulation may be an important factor in early SVHD pathobiology.

Impact of Maternal Obesity on the Gestational Metabolome and Infant Metabolome, Brain, and Behavioral Development in Rhesus Macaques.

Maternal gestational obesity is associated with elevated risks for neurodevelopmental disorder, including autism spectrum disorder. However, the mechanisms by which maternal adiposity influences fetal developmental programming remain to be elucidated. We aimed to understand the impact of maternal obesity on the metabolism of both pregnant mothers and their offspring, as well as on metabolic, brain, and behavioral development of offspring by utilizing metabolomics, protein, and behavioral assays in a non-human primate model. We found that maternal obesity was associated with elevated inflammation and significant alterations in metabolites of energy metabolism and one-carbon metabolism in maternal plasma and urine, as well as in the placenta. Infants that were born to obese mothers were significantly larger at birth compared to those that were born to lean mothers. Additionally, they exhibited significantly reduced novelty preference and significant alterations in their emotional response to stress situations. These changes coincided with differences in the phosphorylation of enzymes in the brain mTOR signaling pathway between infants that were born to obese and lean mothers and correlated with the concentration of maternal plasma betaine during pregnancy. In summary, gestational obesity significantly impacted the infant systemic and brain metabolome and adaptive behaviors.

Longitudinal Serum Metabolomics in Extremely Premature Infants: Relationships With Gestational Age, Nutrition, and Morbidities.

An increasing number of extremely premature infants survive the neonatal period and beyond. Little is known about the maturation of the preterm infant’s metabolome and its relation to the development of morbidities. Using 1H-NMR, we investigated the serum metabolic profile of 87 infants born at a gestational age (GA) <28 weeks [mean GA (SD) 25.4 (1.4) weeks] in samples longitudinally collected from birth to term equivalent age. The infant metabolome was analyzed in relation to GA, postnatal age, nutrition, and preterm morbidities. At postnatal day 1, low GA correlated with high levels of 3-hydroxyisobutyrate, acetate, acetoacetate, acetone, formate, glucose, and valine. Nearly all quantified metabolites displayed postnatal concentration changes. For example, the two phospholipid-related metabolites myo-inositol and ethanolamine displayed a similar decline from birth over the first weeks of life, irrespectively of GA. The proportion of enteral/parenteral energy intake in the first 28 days significantly correlated with mean levels of 52% of the analyzed metabolites. Low enteral energy intake was associated with high serum levels of 3-hydroxyisobutyrate, creatinine, glucose, glycerol, histidine, lactate, leucine, lysine, methionine, ornithine, phenylalanine, proline, threonine, and uridine. There were also significant correlations between high enteral intake and high serum levels of isoleucine and tyrosine. Retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) outcomes were not significantly associated with metabolite levels in the neonatal period after correcting for multiple testing. In conclusion, the serum metabolome of extremely premature infants changes substantially in the neonatal period, largely driven by the gradual transfer from total parenteral nutrition to full enteral feeding. Further studies are needed to disentangle the intricate relationships between the metabolome, nutritional management, GA, and the development of preterm morbidities.

Infant Metabolome in Relation to Prenatal DHA Supplementation and Maternal Single-Nucleotide Polymorphism rs174602: Secondary Analysis of a Randomized Controlled Trial in Mexico

BackgroundAlthough DHA (22:6n–3) is critical for fetal development, results from randomized controlled trials (RCTs) of prenatal DHA supplementation report inconsistent effects on offspring health. Variants in fatty acid desaturase (FADS) genes that regulate the conversion of n–3 and n–6 essential fatty acids into their biologically active derivatives may explain this heterogeneity. ObjectivesWe investigated the effect of prenatal DHA supplementation on the offspring metabolome at age 3 mo and explored differences by maternal FADS single-nucleotide polymorphism (SNP) rs174602. MethodsData were obtained from a double-blind RCT in Mexico [POSGRAD (Prenatal Omega-3 Fatty Acid Supplementation and Child Growth and Development)] in which women (18–35 y old) received DHA (400 mg/d) or placebo from mid-gestation until delivery. Using high-resolution MS with LC, untargeted metabolomics was performed on 112 offspring plasma samples. Discriminatory metabolic features were selected via linear regression (P < 0.05) with false discovery rate (FDR) correction (q = 0.2). Interaction by SNP rs174602 was assessed using 2-factor ANOVA. Stratified analyses were performed, where the study population was grouped into carriers (TT, TC; n = 70) and noncarriers (CC; n = 42) of the minor allele. Pathway enrichment analysis was performed with Mummichog (P < 0.05). ResultsAfter FDR correction, there were no differences in metabolic features between infants whose mothers received prenatal DHA (n = 58) and those whose mothers received placebo (n = 54). However, we identified 343 differentially expressed features in the interaction analysis after FDR correction. DHA supplementation positively enriched amino acid and aminosugars metabolism pathways and decreased fatty acid metabolism pathways among offspring of minor allele carriers and decreased metabolites within the tricarboxylic acid cycle and galactose metabolism pathways among offspring of noncarriers. ConclusionsOur findings demonstrate differences in infant metabolism in response to prenatal DHA supplementation by maternal SNP rs174602 and further support the need to incorporate genetic analysis of FADS polymorphisms into DHA supplementation trials.This trial was registered at http://clinicaltrials.gov as NCT00646360.

Urinary metabolome of infants with colic treated with Lactobacillus reuteri DSM 17938: a pilot randomized trial.

Lactobacillus reuteri DSM 17938 is the only probiotic recommended for treatment of colicky infants, but its mechanism of action is not clear. The study aim was to examine urinary metabolomic fingerprint of colicky breastfed infants before and after 1 month of orally administered Lactobacillus reuteri DSM 17938 or placebo. This randomized, blinded, placebo-controlled clinical trial was carried out with a well-documented probiotic. Thirty-two infants were enrolled, 16 in the probiotic group and 16 in the placebo group. Urine samples were collected from each subject before starting supplementation and at the end of the study period. Metabolomic profiles were obtained using a gas chromatography/mass spectrometry instrument. Subsequently, to compare groups before and after probiotic supplementation, univariate and multivariate statistical analysis were performed. In the L. reuteri treated group all metabolites for all class of nutrients (sugars, amino acids, carboxylic acids) resulted more abundant after the study period. The comparison with a control group (placebo treated), confirmed this effect on urines. The metabolomic analysis of urine samples from infants treated with L. reuteri DSM 17938 allowed to detect some interesting features related to the effect of this treatment on urinary metabolome. To validate the results, a test on a larger cohort is required.

Urinary Metabolomic Profile of Preterm Infants Receiving Human Milk with Either Bovine or Donkey Milk-Based Fortifiers.

Fortification of human milk (HM) for preterm and very low-birth weight (VLBW) infants is a standard practice in most neonatal intensive care units. The optimal fortification strategy and the most suitable protein source for achieving better tolerance and growth rates for fortified infants are still being investigated. In a previous clinical trial, preterm and VLBW infants receiving supplementation of HM with experimental donkey milk-based fortifiers (D-HMF) showed decreased signs of feeding intolerance, including feeding interruptions, bilious gastric residuals and vomiting, with respect to infants receiving bovine milk-based fortifiers (B-HMF). In the present ancillary study, the urinary metabolome of infants fed B-HMF (n = 27) and D-HMF (n = 27) for 21 days was analyzed by 1H NMR spectroscopy at the beginning (T0) and at the end (T1) of the observation period. Results showed that most temporal changes in the metabolic responses were common in the two groups, providing indications of postnatal adaptation. The significantly higher excretion of galactose in D-HMF and of carnitine, choline, lysine and leucine in B-HMF at T1 were likely due to different formulations. In conclusion, isocaloric and isoproteic HM fortification may result in different metabolic patterns, as a consequence of the different quality of the nutrients provided by the fortifiers.

The Effect of Maternal Fatty Acid Desaturase Single Nucleotide Polymorphism rs174602 and Prenatal Supplementation with Docosahexaenoic Acid on the Offspring Metabolome

Abstract Objectives To assess if maternal fatty acid desaturase (FADS) single nucleotide polymorphism (SNP) rs174602 modifies the effect of prenatal DHA supplementation on the offspring metabolome at age 3 months. Methods Data were obtained from POSGRAD, a double-blind randomized controlled trial in Mexico in which 1094 women received 400 mg/day of algal DHA or a placebo (corn and soy oil) from mid-gestation until delivery. Genotyping was performed using maternal blood samples collected from women at baseline. Using liquid chromatography with high-resolution mass spectrometry, untargeted metabolomics was performed on plasma samples obtained from a random subsample of 112 offspring of POSGRAD participants at 3 months of age. Discriminatory metabolic features were selected via linear regression (P &amp;lt; 0.05); false discovery rate (FDR) was controlled for using the Benjamini-Hochberg method (q = 0.2). Analyses were adjusted for infant sex. Effect modification by FADS SNP rs174602 was assessed using two-way analysis of variance. Pathway enrichment analysis was performed with Mummichog (P &amp;lt; 0.05). Subgroup analyses were performed by rs174602, where the study population was grouped into carriers (TT, TC; n = 70) and non-carriers (CC; n = 42) of the minor allele. Results We identified 279 metabolic features that differed significantly between infants whose mothers received prenatal DHA (n = 59) versus placebo (n = 53); however, zero features remained significant after FDR correction. In the DHA * SNP rs174602 interaction analysis, following FDR correction, 346 differentially expressed features were identified. In the subgroup analysis, positively enriched fatty acid metabolism and decreased amino acid and vitamin B3 metabolism pathways were seen among carriers in the DHA group compared to placebo, whereas differentially enriched TCA cycle and omega-6 fatty acid metabolism pathways were observed by treatment group among non-carriers. Conclusions Maternal SNP rs174602 modified the effect of prenatal DHA supplementation on the infant metabolome at 3 months of age, particularly with regards to fatty acid metabolism. These findings provide additional support for the suggestion that differences in FADS genotype may explain inconsistent results observed across DHA supplementation trials. Funding Sources NIH, Nutricia Foundation, Laney Graduate School, and Conacyt, Mexico.

Plasma metabolomic profiles associated with infant food allergy with further consideration of other early life factors

BackgroundFatty acids have been implicated in early life immune development. Food allergy provides a clear phenotype of early allergic disease. Fish oil and vitamin D have immune-modulating properties. We aimed to identify the metabolomic profile of (i) infant food allergy and (ii) factors linked to food allergy in past studies such as fish oil supplementation and serum 25OHD3 levels in early life. MethodsNMR was used to quantify 73 metabolites in plasma of 1 year old infants from the Barwon Infant Study (n=485). Logistic regression models were used to examine associations between infant metabolome and food allergy in infants. Linear regression models were used to describe associations between maternal fish oil supplementation and 25OHD3 levels with infant metabolites. ResultsA higher linoleic acid: total fatty acid (FA) ratio and phenylalanine level were associated with higher odds of food allergy. Antenatal fish oil supplementation was positively associated with docosahexaenoic acid (DHA) and omega-3 related metabolite levels. Postnatal 25OHD3 levels at 1 year of age were positively associated with several FA measures and creatinine and inversely with the saturated FA: total FA ratio. Only the postnatal 25OHD3 patterns persisted after adjustment for multiple comparisons. ConclusionsInfants with food allergy had altered fatty acid profiles at one year. Fish oil supplementation in pregnancy was associated with higher DHA and omega-3 related metabolites at 1 year of age. Associations were modest and the most robustly altered metabolomic profiles were with postnatal 25OHD3 levels.

Fecal microbiome and metabolome of infants fed bovine MFGM supplemented formula or standard formula with breast-fed infants as reference: a randomized controlled trial

Human milk delivers an array of bioactive components that safeguard infant growth and development and maintain healthy gut microbiota. Milk fat globule membrane (MFGM) is a biologically functional fraction of milk increasingly linked to beneficial outcomes in infants through protection from pathogens, modulation of the immune system and improved neurodevelopment. In the present study, we characterized the fecal microbiome and metabolome of infants fed a bovine MFGM supplemented experimental formula (EF) and compared to infants fed standard formula (SF) and a breast-fed reference group. The impact of MFGM on the fecal microbiome was moderate; however, the fecal metabolome of EF-fed infants showed a significant reduction of several metabolites including lactate, succinate, amino acids and their derivatives from that of infants fed SF. Introduction of weaning food with either human milk or infant formula reduces the distinct characteristics of breast-fed- or formula-fed- like infant fecal microbiome and metabolome profiles. Our findings support the hypothesis that higher levels of protein in infant formula and the lack of human milk oligosaccharides promote a shift toward amino acid fermentation in the gut. MFGM may play a role in shaping gut microbial activity and function.

Association of infant formula composition and anthropometry at 4 years: Follow-up of a randomized controlled trial (BeMIM study).

The relationships between nutrition, metabolic response, early growth and later body weight have been investigated in human studies. The aim of this follow-up study was to assess the long-term effect of infant feeding on growth and to study whether the infant metabolome at the age of 4 months might predict anthropometry at 4 years of age. The Belgrade-Munich infant milk trial (BeMIM) was a randomized controlled trial in which healthy term infants received either a protein-reduced infant formula (1.89 g protein/100 kcal) containing alpha-lactalbumin enriched whey and long-chain polyunsaturated fatty acids (LC-PUFA), or a standard formula (2.2 g protein/100 kcal) without LC-PUFA, focusing on safety and suitability. Non-randomized breastfed infants were used as a reference group. Of the 259 infants that completed the BeMIM study at the age of 4 months (anthropometry assessment and blood sampling), 187 children participated in a follow-up visit at 4 years of age. Anthropometry including weight, standing height, head circumference, and percent body fat was determined using skinfolds (triceps, subscapular) and bioelectrical impedance analysis. Plasma metabolite concentration, collected in samples at the age of 4 months, was measured using flow-injection tandem mass spectrometry. A linear regression model was applied to estimate the associations between each metabolite and growth with metabolites as an independent variable. At 4 years of age, there were no significant group differences in anthropometry and body composition between formula groups. Six metabolites (Asn, Lys, Met, Phe, Trp, Tyr) measured at 4 months of age were significantly associated with changes in weight-for-age z-score between 1 to 4 months of age and BMI-for-age z-score (Tyr only), after adjustment for feeding group. No correlation was found between measured metabolites and long-term growth (up to 4 years of age). No long-term effects of early growth patterns were shown on anthropometry at 4 years of age. The composition of infant formula influences the metabolic profile and early growth, while long-term programming effects were not observed in this study.

Effects of Early Nutrition on the Infant Metabolome.

Breastfeeding induces a different metabolic and endocrine response than feeding conventional infant formula, and it has also been associated with slower weight gain and reduced disease risk in later life. The underlying programming mechanisms remain to be explored. Breastfeeding has been reported to induce lower levels of insulin, insulin-like growth factor-1 and some amino acids (AAs) than formula feeding. In the Childhood Obesity Project (CHOP), infants fed a conventional protein-rich formula had a higher BMI at 2 and 6 years than those fed a protein-reduced formula. At 6 months, higher protein intakes induced increased plasma concentrations of branched-chain AAs (BCAAs) and their oxidation products, short-chain acylcarnitines. With increasing BCAA levels, these short-chain acylcarnitines increased proportionally only until a break point was reached, after which BCAAs seemed to escape their degradation. The resulting marked elevation in BCAA levels with high-protein (HP) intakes appears to contribute to increased insulin levels and to affect β-oxidation of fatty acids. The ratios of long-chain acylcarnitines to free carnitine decreased in infants who received a HP formula, which indicates a reduced initiation of β-oxidation. We conclude that HP intakes inducing high BCAA plasma levels may inhibit fat oxidation and thereby enhance body fat deposition and adiposity.

Effect of lactose on gut microbiota and metabolome of infants with cow’s milk allergy

Allergic infants have an unusual gastrointestinal microbiota with low numbers of Bifidobacterium/Lactobacilli and high levels of Clostridium, staphylococci and Escherichia coli. Hydrolyzed formula used to treat these infants is deprived of lactose that instead may influence the gut microbial composition. The aim of the present study is to investigate the influence of lactose on the composition of the gut microbiota and metabolome of infants with cow's milk allergy. Infants prospectively enrolled received an extensively hydrolyzed formula with no lactose for 2 months followed by an identical lactose-containing formula for an additional 2 months. Healthy, age-gender-matched infants were used as controls. The following determinations were performed before and after the introduction of lactose in the diet: enumeration of cells present in the feces using FISH, counts of viable bacterial cells and gas-chromatography mass spectrometry/solid-phase microextraction analysis. The addition of lactose to the diet significantly increases the counts of Bifidobacteria and lactic acid bacteria (p < 0.01), decreases that of Bacteroides/clostridia (p < 0.05) reaching counts found in healthy controls; lactose significantly increases the concentration of total short-chain fatty acids (p < 0.05). The addition of lactose to an extensively hydrolyzed formula is able to positively modulate the composition of gut microbiota by increasing the total fecal counts of Lactobacillus/Bifidobacteria and decreasing that of Bacteroides/Clostridia. The positive effect is completed by the increase of median concentration of short chain fatty acids, especially for acetic and butyric acids demonstrated by the metabolomic analysis.

Developmental origins of obesity: Early feeding environments, infant growth, and the intestinal microbiome

Pediatric overweight and obesity are growing problems worldwide, with increasing prevalence among even infants and young children. The refractory nature of early overweight necessitates identifying the factors contributing to early excess weight gain for successful intervention. Early feeding practices may be particularly important in shaping long-term vulnerability to obesity. How and what infants are fed can influence weight gain, adiposity, and energy metabolism during infancy and across the life course through a number of interacting physiological and behavioral pathways. This article argues that these biological mechanisms interact with the social and behavioral context of infant feeding to create differential vulnerability to later obesity. This article reviews recent research on the potential mechanisms linking infant feeding and risk of later obesity, focusing on the emerging role of microflora colonization. The nutritive and non-nutritive components of breastmilk, formula and solid foods and the practices surrounding feeding shape the infant metabolome, programming growth rates and body composition, altering metabolism and physiology, promoting differential microfloral colonization, and shaping behavioral responses to foods and eating. The occurrence of chronic disease precursors at increasingly younger ages and the tendency of overweight young children to become overweight adolescents and adults underscore the importance of understanding this complex early exposure and intervening early to prevent the development of obesity in increasingly weight-promoting environments.