scholarly journals Stool pH and Short/Branched Chain Fatty Acids in Infants Receiving Extensively Hydrolyzed Formula, Amino Acid Formula, or Human Milk Through Two Months of Age (P11-076-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Car Reen Kok ◽  
Bradford Brabec ◽  
Maciej Chichlowski ◽  
Cheryl Harris ◽  
Nancy Moore ◽  
...  

Abstract Objectives Infant feeding influences early development of the gut microbiome, colonization pattern, and community structure. Metabolites, including short- and branched-chain fatty acids (S/BCFA) (e.g., butyrate, propionate), produced by colonic bacteria serve as signaling molecules, influence immunity, and reduce luminal pH in the gastrointestinal environment. The objective of this study was to evaluate stool S/BCFA and pH in infants fed with different sources of dietary protein. Methods In this multicenter, double-blind, controlled, parallel-group, pilot study, healthy term infants were randomized to receive one of two infant formulas (IF): amino-acid based (AAF; n = 25) or extensively hydrolyzed cow's milk protein (EHF; n = 28) from Baseline (1-7 days of age) up to 60 days of age. A human milk reference group (HM; n = 25) received mother's own milk over the same period. Diethyl ether extractions of S/BCFA from stool samples (Baseline, Day 30, and Day 60) were quantified by gas chromatography (Clarus 580; PerkinElmer) using a fused silica capillary column (Nukol 30m × 0.25mm id × 0.25μm film). Mean stool S/BCFA (μmol/g) and pH were analyzed by repeated measures analysis of variance (ANOVA). Results Complete stool data (all study time points) were available for 49 participants. Stool pH (∼6) was similar among groups at Baseline with no significant changes for HM and EHF groups through Day 60. The AAF group was significantly higher at Days 30 and 60 (Figure 1). Total SCFA were similar for all groups through Day 60. Butyrate increased significantly from Baseline to Day 60 in the EHF group (P = 0.026) and was significantly higher vs HM at Days 30 and 60 (P = 0.0009 and 0.0004 respectively). Butyrate was significantly higher for AAF vs HM at Day 60 only (P = 0.038). Propionate was significantly higher for EHF and AAF at Day 30 (P = 0.0009 and < 0.0001 respectively) and AAF only at Day 60 (P = 0.005) vs HM. Total and individual BCFA increased for AAF and EHF groups vs HM through Day 60. Conclusions Distinct patterns of pH and microbial metabolites were demonstrated for infants receiving mother's own milk compared to amino acid-based or extensively hydrolyzed protein formula. Providing different sources of dietary protein early in life may influence gut microbiota and metabolites. Funding Sources Mead Johnson Pediatric Nutrition Institute. Supporting Tables, Images and/or Graphs

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Car Reen Kok ◽  
Bradford Brabec ◽  
Maciej Chichlowski ◽  
Cheryl L. Harris ◽  
Nancy Moore ◽  
...  

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.


2018 ◽  
Author(s):  
Stefan Zdraljevic ◽  
Bennett W. Fox ◽  
Christine Strand ◽  
Oishika Panda ◽  
Francisco J. Tenjo ◽  
...  

AbstractWe find that variation in thedbt-1gene underlies natural differences inCaenorhabditis elegansresponses to the toxin arsenic. This gene encodes the E2 subunit of the branched-chain α-keto acid dehydrogenase (BCKDH) complex, a core component of branched-chain amino acid (BCAA) metabolism. We causally linked a non-synonymous variant in the conserved lipoyl domain of DBT-1 to differential arsenic responses. Using targeted metabolomics and chemical supplementation, we demonstrate that differences in responses to arsenic are caused by variation in iso-branched chain fatty acids. Additionally, we show that levels of branched chain fatty acids in human cells are perturbed by arsenic treatment. This finding has broad implications for arsenic toxicity and for arsenic-focused chemotherapeutics across human populations. Our study implicates the BCKDH complex and BCAA metabolism in arsenic responses, demonstrating the power ofC. elegansnatural genetic diversity to identify novel mechanisms by which environmental toxins affect organismal physiology.


2019 ◽  
Vol 85 (9) ◽  
Author(s):  
Xuedan Wang ◽  
Glenn R. Gibson ◽  
Adele Costabile ◽  
Manuela Sailer ◽  
Stephan Theis ◽  
...  

ABSTRACTMetabolism of protein by gut bacteria is potentially detrimental due to the production of toxic metabolites, such as ammonia, amines,p-cresol, and indole. The consumption of prebiotic carbohydrates results in specific changes in the composition and/or activity of the microbiota that may confer benefits to host well-being and health. Here, we have studied the impact of prebiotics on proteolysis within the gutin vitro. Anaerobic stirred batch cultures were inoculated with feces from omnivores (n = 3) and vegetarians (n = 3) and four protein sources (casein, meat, mycoprotein, and soy protein) with and without supplementation by an oligofructose-enriched inulin. Bacterial counts and concentrations of short-chain fatty acids (SCFA), ammonia, phenol, indole, andp-cresol were monitored during fermentation. Addition of the fructan prebiotic Synergy1 increased levels of bifidobacteria (P = 0.000019 and 0.000013 for omnivores and vegetarians, respectively). Branched-chain fatty acids (BCFA) were significantly lower in fermenters with vegetarians’ feces (P = 0.004), reduced further by prebiotic treatment. Ammonia production was lower with Synergy1. Bacterial adaptation to different dietary protein sources was observed through different patterns of ammonia production between vegetarians and omnivores. In volunteer samples with high baseline levels of phenol, indole,p-cresol, and skatole, Synergy1 fermentation led to a reduction of these compounds.IMPORTANCEDietary protein intake is high in Western populations, which could result in potentially harmful metabolites in the gut from proteolysis. In anin vitrofermentation model, the addition of prebiotics reduced the negative consequences of high protein levels. Supplementation with a prebiotic resulted in a reduction of proteolytic metabolites in the model. A difference was seen in protein fermentation between omnivore and vegetarian gut microbiotas: bacteria from vegetarian donors grew more on soy and Quorn than on meat and casein, with reduced ammonia production. Bacteria from vegetarian donors produced less branched-chain fatty acids (BCFA).


1972 ◽  
Vol 8 (1) ◽  
pp. 42-55 ◽  
Author(s):  
Heinz Egge ◽  
Uwe Murawski ◽  
Ragnar Ryhage ◽  
Paul György ◽  
Wirapong Chatranon ◽  
...  

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Stefan Zdraljevic ◽  
Bennett William Fox ◽  
Christine Strand ◽  
Oishika Panda ◽  
Francisco J Tenjo ◽  
...  

We find that variation in the dbt-1 gene underlies natural differences in Caenorhabditis elegans responses to the toxin arsenic. This gene encodes the E2 subunit of the branched-chain α-keto acid dehydrogenase (BCKDH) complex, a core component of branched-chain amino acid (BCAA) metabolism. We causally linked a non-synonymous variant in the conserved lipoyl domain of DBT-1 to differential arsenic responses. Using targeted metabolomics and chemical supplementation, we demonstrate that differences in responses to arsenic are caused by variation in iso-branched chain fatty acids. Additionally, we show that levels of branched chain fatty acids in human cells are perturbed by arsenic treatment. This finding has broad implications for arsenic toxicity and for arsenic-focused chemotherapeutics across human populations. Our study implicates the BCKDH complex and BCAA metabolism in arsenic responses, demonstrating the power of C. elegans natural genetic diversity to identify novel mechanisms by which environmental toxins affect organismal physiology.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1808
Author(s):  
Iris Trefflich ◽  
Stefan Dietrich ◽  
Annett Braune ◽  
Klaus Abraham ◽  
Cornelia Weikert

A vegan diet could impact microbiota composition and bacterial metabolites like short-chain (SCFA) and branched-chain fatty acids (BCFA). The aim of this study was to compare the concentrations of SCFA, BCFA, ammonia, and fecal pH between vegans and omnivores. In this cross-sectional study (vegans n = 36; omnivores n = 36), microbiota composition, fecal SCFA, BCFA, and ammonia concentrations and pH were analyzed in complete stool samples. A random forest regression (RFR) was used to identify bacteria predicting SCFA/BCFA concentrations in vegans and omnivores. No significant differences in SCFA and BCFA concentrations were observed between vegans and omnivores. Fecal pH (p = 0.005) and ammonia concentration (p = 0.01) were significantly lower in vegans than in omnivores, while fiber intake was higher (p < 0.0001). Shannon diversity was higher in omnivores compared to vegans on species level (p = 0.04) only. In vegans, a cluster of Faecalibacterium prausnitzii, Prevotella copri, Dialister spp., and Eubacterium spp. was predictive for SCFA and BCFA concentrations. In omnivores, Bacteroides spp., Clostridium spp., Ruminococcus spp., and Prevotella copri were predictive. Though SCFA and BCFA did not differ between vegans and omnivores, the results of the RFR suggest that bacterial functionality may be adapted to varying nutrient availability in these diets.


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