scholarly journals Galactose and Sialo-galactose Modifications in Glycoproteins on the Surface of Bovine Milk Exosome Are Essential for Exosome Uptake in Non-bovine Species (OR34-07-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sonal Sukreet ◽  
Bruno Vieira Resende E Silva ◽  
Jiri Adamec ◽  
Juan Cui ◽  
Janos Zempleni
Keyword(s):  
Binding Sites ◽  
Bovine Milk ◽  
Surface Proteins ◽  
Conditional Knockout ◽  
Funding Sources ◽  
Eastern Blotting ◽  
Gates Foundation ◽  
Distribution Studies ◽  
Bovine Species ◽  
Human Intestinal Cells

Abstract Objectives Exosomes are natural nanoparticles that can be found in most body fluids including milk. Bovine milk exosomes (BME) are bioavailable and transfer cargos such as RNAs, lipids and proteins across species boundaries. Previous competitor studies implicated galactose-modifications in exosome surface proteins in exosome transport. The objectiveof our study was to assess the importance of glycan modifications in BME surface glycoproteins for BME uptake and distribution in human intestinal cells (FHs cells) and mice. Methods BME were isolated from milk by differential centrifugation (Fig. 1). Putative glycan binding sites on the surfaces of BME were identified by LC/MS-MS and bioinformatics protocols and confirmed by eastern blotting. Surface glycans were altered using proteases, glycosidases and blocking of glycans with lectins for subsequent transport and distribution studies (Table 1). The uptake of BME by FHs cells was assessed using membrane and RNA cargo-labeled BME. The distribution of BME in mice was assessed using BME transfected with fluorophore (IRDye)-labeled synthetic miR-320a in C57BL/6 mice and MGAT-1 tamoxifen inducible conditional knockout (CKO) mice ages 5–8 weeks. One-way ANOVA and Bonferroni's multiple comparison were used for statistical analyses; P < 0.05 was considered significant. Results We identified 49 (N), 13 (O) and 13 (C) putative glycan binding sites on the BME surface, and confirmed the presence of mannose, galactose, N-acetylgalactose, fucose and neuraminate (Fig. 2). Galactose and N-acetylgalactosamine residues on the surface of BME were of particular importance for their uptake by FHs cells, whereas N-acetylglucosamine on the surface of FHs cells was more important than other glycans for BME uptake (Fig. 3). Enzymatic and genetic removal of glycans in BME and MGAT-1 CKO, respectively, caused a loss of BME accumulation in murine livers and pancreas (Fig. 4). Conclusions Distinct glycan features are essential for the uptake of BME in mice. The study laid a foundation to assess the importance of glycan modifications in infant formulas and the homing of drug-loaded exosomes to sites of disease. Funding Sources NIFA, NIH, Bill & Melinda Gates Foundation, PureTech Health, and USDA Hatch & Multistate. J.Z. is a consultant for PureTech. Supporting Tables, Images and/or Graphs

scholarly journals Bovine mRNAs in Cow's Milk Exosomes Are Bioavailable and Translated into Peptides in Non-bovine Systems (P06-030-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Di Wu ◽  
Jiang Shu ◽  
Camila Braga Pereira ◽  
Juan Cui ◽  
Jiri Adamec ◽  
...  
Keyword(s):  
Bovine Milk ◽  
Cell Communication ◽  
Mrna Translation ◽  
Amino Acid Sequences ◽  
Food Allergies ◽  
Two Dimensional ◽  
Two Dimensional Gel Electrophoresis ◽  
Funding Sources ◽  
Rabbit Reticulocyte Lysate System ◽  
Gates Foundation

Abstract Objectives Exosomes are natural nanoparticles that participate in cell-to-cell communication by transferring regulatory molecules such as microRNAs from donor cells to recipient cells. Previously, we have demonstrated that exosomes and microRNAs are not exclusively obtained from endogenous synthesis but may also be absorbed from milk. We assessed whether 1) exosomes contain mRNAs (i.e., RNAs other than microRNAs), 2) mRNAs are bioavailable in mice, and 3) bovine mRNAs are translated into peptides. Methods For mRNA analysis, exosomes were isolated from bovine milk using differential ultracentrifugation, and RNA cargos were analyzed by RNA-sequencing. For bioavailability analysis, a synthetic fragment of fluorophore (IRDye)-labeled bovine CSN3 mRNA was transfected into bovine milk exosomes, which were administered to Balb/c mice by oral gavage. Tissues distribution of CSN3 mRNA was assessed 24 h after gavage by using a LiCor Odyssey CLx imager. For analysis of mRNA translation, mRNA from bovine milk exosomes were translated using the rabbit reticulocyte lysate system and BODIPY-labeled lysine. Peptides were separated by two-dimensional gel electrophoresis and fluorescence was visualized using a Typhoon FLA 7000 scanner. Statistical analysis, NA. Results We detected > 3600 bovine mRNAs in exosomes. Most mRNAs were truncated; 107 mRNAs contained their natural ATG start codons. Thirteen of these mRNAs, including CSN3, encoded bovine proteins and peptides with amino acid sequences distinct from those in human and murine orthologs (Table 1). Mice absorbed CSN3 mRNA encapsulated in milk exosomes, which accumulated primarily in the liver (Fig. 1). Nine bovine peptide spots were detected by two-dimensional electrophoresis (Fig. 2). Conclusions Bovine milk exosomes contain mRNAs which are bioavailable and translated into peptides in non-bovine systems. We speculate that food mRNAs might play a role in food allergies and immune tolerance. Future studies: Identification of peptides by LC/MS-MS is in progress. We will assess the relevance of mRNA translation for allergies and tolerance in animal models. Funding Sources NIFA, NIH, Gates Foundation, PureTech, Inc. and USDA Hatch and Multistate. J.Z. is a consultant for PureTech. Supporting Tables, Images and/or Graphs

scholarly journals Sonication and Short-term Incubation Alter the Content of Bovine Milk Exosome Cargos and Exosome Bioavailability (OR26-08-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sonal Sukreet ◽  
Bruno Vieira Resende E Silva ◽  
Jiri Adamec ◽  
Juan Cui ◽  
Janos Zempleni
Keyword(s):  
Bovine Milk ◽  
Cell Communication ◽  
Intestinal Transport ◽  
Small Rna Sequencing ◽  
Short Term ◽  
Funding Sources ◽  
Marker Proteins ◽  
Donor Cells ◽  
Significant Difference ◽  
Gates Foundation

Abstract Objectives Exosomes are endogenous nanoparticles that participate in cell-to-cell communication through the transfer of cargos such RNAs, lipids and proteins from donor cells to recipient cells. Previously, we showed that mammals absorb exosomes from milk. Ultrasonication causes a transient disruption of the exosome membranes, leading to loss of microRNAs. When mice were fed diets based on the AIN-93G formulation, modified to contain a physiological amount of milk exosomes (exosome and RNA-sufficient diet, ERS) or sonicated exosomes (exosome and RNA-depleted diet, ERD), we observed a loss of circulating and tissue microRNAs and phenotypes such as aberrant purine metabolism. The objective of this study was to conduct a comprehensive analysis ofthe effects of sonication on exosomes cargos and bioavailability, thereby generating insights into mechanisms through which ERD elicits phenotypes. Methods Exosomes were isolated from ultrasonicated (USE) and non-sonicated (NSE) bovine milk by ultracentrifugation and authenticated following guidelines of the International Society for Extracellular Vesicles. MicroRNAs were analyzed by small RNA-sequencing. Lipids and proteins were analyzed by LC/MS-MS. Intestinal transport was assessed using FM 4-64-labeled exosomes in primary human small intestine cells (FHs cells). Bioavailability of exosomes transfected with IRDye-labeled miR-320a was assessed using oral gavage in C57BL/6 mice.The unpaired t-test was used for statistical analysis P < 0.05 was considered statistically significant. Results Ultrasonication affected the vesicle count and exosome morphology. Western blot analysis detected marker proteins only in NSE. The content of microRNAs was about 93% lower in USE than NSE. Significant difference was noted for lipid and protein identities between NSE and USE. Reduced uptake of USE by intestinal cells and loss of cargo accumulation in murine livers and pancreas for USE compared to NSE (Fig. 1-5). Conclusions Ultrasonication causesa loss of microRNAs in milk exosomes. The unique patterns of proteins and lipids likely is due to an exchangeof membranes between exosomes and other vesicles during ultrasonication, which might explain the lower bioavailability of USE compared to NSE. We currently test the exchange of lipids during ultrasonication. Funding Sources NIFA, NIH, Gates Foundation, PureTech, Inc. and USDA Hatch and Multistate. J.Z. is a consultant for PureTech. Supporting Tables, Images and/or Graphs

scholarly journals Fibrinolysis: A Primordial System Linked to the Immune Response

2021 ◽  
Vol 22 (7) ◽  
pp. 3406
Author(s):  
Robert L. Medcalf ◽  
Charithani B. Keragala
Keyword(s):  
Binding Sites ◽  
Defense Mechanisms ◽  
Immune Cell ◽  
Immune Defense ◽  
Surface Proteins ◽  
Cell Behavior ◽  
Phylogenetic Studies ◽  
Blood Clots ◽  
Lower Vertebrates ◽  
Almost All

The fibrinolytic system provides an essential means to remove fibrin deposits and blood clots. The actual protease responsible for this is plasmin, formed from its precursor, plasminogen. Fibrin is heralded as it most renowned substrate but for many years plasmin has been known to cleave many other substrates, and to also activate other proteolytic systems. Recent clinical studies have shown that the promotion of plasmin can lead to an immunosuppressed phenotype, in part via its ability to modulate cytokine expression. Almost all immune cells harbor at least one of a dozen plasminogen receptors that allows plasmin formation on the cell surface that in turn modulates immune cell behavior. Similarly, a multitude of pathogens can also express their own plasminogen activators, or contain surface proteins that provide binding sites host plasminogen. Plasmin formed under these circumstances also empowers these pathogens to modulate host immune defense mechanisms. Phylogenetic studies have revealed that the plasminogen activating system predates the appearance of fibrin, indicating that plasmin did not evolve as a fibrinolytic protease but perhaps has its roots as an immune modifying protease. While its fibrin removing capacity became apparent in lower vertebrates these primitive under-appreciated immune modifying functions still remain and are now becoming more recognised.

scholarly journals Interaction of single-chain urokinase with its receptor induces the appearance and disappearance of binding epitopes within the resultant complex for other cell surface proteins

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 542-551 ◽  
Author(s):  
AA Higazi ◽  
RH Upson ◽  
RL Cohen ◽  
J Manuppello ◽  
J Bognacki ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Surface ◽  
Binding Sites ◽  
Ldl Receptor ◽  
Cell Types ◽  
Surface Proteins ◽  
Single Chain ◽  
Cell Surface Proteins ◽  
Functional Changes ◽  
And Migration

Binding of urokinase-type plasminogen activator (uPA) to its glycosylphosphatidylinositol-anchored receptor (uPAR) initiates signal transduction, adhesion, and migration in certain cell types. To determine whether some of these activities may be mediated by associations between the uPA/uPAR complex and other cell surface proteins, we studied the binding of complexes composed of recombinant, soluble uPA receptor (suPAR) and single chain uPA (scuPA) to a cell line (LM-TK- fibroblasts) that does not express glycosylphosphatidylinositol (GPI)-anchored proteins to eliminate potential competition by endogenous uPA receptors. scuPA induced the binding of suPAR to LM-TK- cells. Binding of labeled suPAR/scuPA was inhibited by unlabeled complex, but not by scuPA or suPAR added separately, indicating cellular binding sites had been formed that are not present in either component. Binding of the complex was inhibited by low molecular weight uPA (LMW-uPA) indicating exposure of an epitope found normally in the isolated B chain of two chain uPA (tcuPA), but hidden in soluble scuPA. Binding of LMW-uPA was independent of its catalytic site and was associated with retention of its enzymatic activity. Additional cell binding epitopes were generated within suPAR itself by the aminoterminal fragment of scuPA, which itself does not bind to LM-TK- cells. When scuPA bound to suPAR, a binding site for alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP) was lost, while binding sites for cell-associated vitronectin and thrombospondin were induced. In accord with this, the internalization and degradation of cell-associated tcuPA and tcuPA-PAI- 1 complexes proceeded less efficiently in the presence of suPAR. Further, little degradation of suPAR was detected, suggesting that cell- bound complex dissociated during the initial stages of endocytosis. Thus, the interaction of scuPA with its receptor causes multiple functional changes within the complex including the dis-appearance of an epitope in scuPA involved in its clearance from the cell surface and the generation of novel epitopes that promote its binding to proteins involved in cell adhesion and signal transduction.

scholarly journals Harmonization of Maternal Nutrition Trials – Finding and Creating Similarities in Protocols and Outcomes

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1738-1738
Author(s):  
Alison Gernand ◽  
Yemane Berhane ◽  
Nita Bhandari ◽  
Ranadip Chowdhury ◽  
Fyezah Jehan ◽  
...  
Keyword(s):  
Data Analysis ◽  
Gestational Age ◽  
Maternal Nutrition ◽  
Time Frame ◽  
Protein Supplementation ◽  
Fetal Biometry ◽  
Funding Sources ◽  
Biospecimen Collection ◽  
Gates Foundation ◽  
Meta Analyses

Abstract Objectives Public health and clinical recommendations should be based on results from multiple studies, however trials often have outcomes that are not defined in the same way. This project aims to harmonize selected protocols, outcome definitions, and data analysis across five randomized trials of antenatal balanced energy-protein supplementation being conducted in Burkina Faso, Ethiopia, India, Nepal, and Pakistan. Methods Harmonization efforts include a range of activities from reviewing detailed protocols, biospecimen collection plans, data dictionaries, and data analysis plans to proposing best practices and acceptable practices based on field limitations. Most studies have not begun or are early in enrollment, an ideal time frame to make changes. A two-day workshop of lead investigators, content experts and advisors will be held in late February, and harmonization activities will continue thereafter. Results All studies are examining anthropometry at birth as a primary outcome, however the timing of birth measurements (hours since birth) and types of measurements taken differ across trials. All studies are estimating gestational age by ultrasound measurements, but the gestational age at ultrasound differs (in part due to differences in timing of antenatal care by country) as well as the number of fetal biometry measures. Finally, stillbirth is a key outcome across trials, but initial definitions had slight differences that will now be harmonized. We are also able to add new, important maternal and child health outcomes to each trial that will have the same protocols from inception (e.g., microbiome). Conclusions Efforts thus far have resulted in communication between study investigators, consideration of improved protocols, and addition of new outcomes to collect across all sites. Further results are forthcoming after the February workshop, which will include documentation of how much definitions vary across studies and the challenges of standardization. We expect the harmonization process to improve overall reporting within each study and provide opportunities for better meta-analyses. Funding Sources The Bill and Melinda Gates Foundation.

scholarly journals Nutritional Iron Deficiency and Malaria: Impact of a Public-Private Partnership

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 837-837
Author(s):  
Patricia Haggerty ◽  
Daniel Raiten
Keyword(s):  
Iron Deficiency ◽  
Public Private Partnership ◽  
Lessons Learned ◽  
The Novel ◽  
Private Partnership ◽  
Funding Sources ◽  
Novel Approach ◽  
Research Track ◽  
Gates Foundation ◽  
The Impact

Abstract Objectives Background: In 2007 the Bill and Melinda Gates Foundation (BMGF) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) collaborated to address concerns about the safety and efficacy of interventions to prevent and treat nutritional iron deficiency (NID) particularly in the context of malaria. The “Iron and Malaria Project” (IMP) addressed how iron might not be safe, iron assessment, and the value of interventions to address NID. This presentation will: Describe the novel approach used to achieve the IMP goals, describe the IMP accomplishments and impacts, and summarize lessons learned. Methods The IMP had: 1) Research Track: NICHD initiated 2 funding opportunity announcements resulting in 10 funded projects; 2) Translation Track: a) consultations with global stakeholders; b) risk: benefit analyses on the use of interventions to prevent and treat NID; c) a collaboration with the CDC to develop standards for a sTfR assay; d) the BOND project to harmonize the process for discovery, development and deployment of nutrient biomarkers; e) the INSPIRE project, a review of extant evidence on reciprocal relationships between nutrition and inflammation; and f) the BRINDA project, a collaboration with the CDC, GAIN, and WHO to study the impact of inflammation on interpretation of biomarkers of iron and other determinants of anemia and develop approaches to account for this interaction. Results Funded grants included 4 basic science projects exploring mechanisms to explain iron and malaria interactions and 6 clinical studies addressing various aspects of the iron malaria relationship. To date, 72 journal publications have resulted. Using the NIH Relative Citation Ratio metric, 2/3 have scientific influence scores ≥the 50th percentile of all NIH-funded research publications and 15 have scores ≥ the 90th percentile. Conclusions The IMP leveraged the attributes of this public-private partnership between BMGF and NICHD/NIH to accomplish its goals. The partnership's complementarity and synergy resulted in broad traction and collaboration with a global community invested in solving the challenges of iron and malaria. Funding Sources BMGF $9.3 million, NIH Office of Dietary Supplements $1.3 million.

scholarly journals Assessing the Coverage of Biofortified Foods: Development and Testing of Methods and Indicators in Musanze, Rwanda

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1833-1833
Author(s):  
Nicolai Petry ◽  
James Wirth ◽  
Valerie Friesen ◽  
Fabian Rohner ◽  
Arcade Nkundineza ◽  
...  
Keyword(s):  
Urban Areas ◽  
Large Scale ◽  
Household Survey ◽  
Test Methods ◽  
Food Fortification ◽  
Program Performance ◽  
Sweet Potatoes ◽  
Cross Sectional ◽  
Funding Sources ◽  
Gates Foundation

Abstract Objectives Biofortification is a promising approach to increase micronutrient intakes, especially among populations that are hard to reach with other interventions. Information on the coverage of biofortified foods is needed to ascertain potential for impact, understand program performance, and identify bottlenecks. In this study, we aimed to develop and test methods and indicators for assessing household coverage of biofortified foods. Methods We developed five recall-based indicators of household coverage to assess biofortification programs building on approaches previously used to assess targeted and large-scale food fortification programs. These were: 1) consumption of the food; 2) awareness of the biofortified food; 3) availability of the biofortified food; 4) consumption of the biofortified food (ever); and 5) consumption of the biofortified food (current). We tested these indicators in a cross-sectional, cluster, household survey in 20 rural and five peri-urban areas in Musanze, Rwanda where two biofortification programs, i.e., biofortified beans and orange fleshed sweet potatoes (OFSP), were implemented. Results Among the 242 households surveyed, consumption of beans and sweet potatoes was high (99% and 96%, respectively) while awareness of biofortified beans or OFSP was 66% and 49%, respectively, and availability was 24% and 11%, respectively. Overall, 15% and 11% of households had ever consumed biofortified beans and OFSP, respectively, and 10% and 2% of households were currently consuming them, respectively. The major bottlenecks to coverage were awareness and availability of the biofortified foods. Conclusions The proposed methods and indicators fill a gap in the availability of tools to assess biofortification program coverage and the results of the survey highlight their utility for assessing program performance and identifying bottlenecks. Further testing is warranted to confirm the generalizability of the coverage indicators and inform their operationalization when deployed in different contexts. Funding Sources Bill & Melinda Gates Foundation.

scholarly journals Quadruple Fortification of Salt with Iodine, Iron, Vitamins B9 and B12 to Reduce Maternal and Neonatal Mortality by Reducing Anemia and Nutritional Deficiency Prevalence (P24-041-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Venkatesh Mannar ◽  
Levente Diosady
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Pilot Scale ◽  
Iron Core ◽  
Ferrous Fumarate ◽  
Funding Sources ◽  
Spray Solution ◽  
Solid Iron ◽  
Gates Foundation ◽  
Average Size

Abstract Objectives To develop a quadruple fortified salt(QFS) formulation that provides100 + % of RDA for iodine and vitamin B12 and 30–50% of RDA for iron and folic acid in forms that are organoleptically stable, bioavailable and acceptable to consumers Methods Iodine was sprayed onto salt as an aqueous solution of potassium iodate. Iron was admixed as a solid premix, which was colour masked with TiO2 and encapsulated in soy stearine to provide a water-impervious coating. The iron core was made of ferrous fumarate, which was agglomerated to an average size matching salt grain, i.e., 300–500 µm. Folic acid and vitamin B12 were added either in the iodate spray solution or in the solid iron premix. The premixes and salt were stored at 25, 35 and 45°C at 65% RH for up to a year. The loss of iodine, folic acid and vitamin B12 were monitored. An optimized formulation was tested on the pilot scale at JVS Foods Pvt, Jaipur, India. Results Folic acid can be stabilized in the iodine spray solution, and triple fortified salt containing iodine, folic acid and encapsulated ferrous fumarate retained >90% of both the added iodine and folic acid for 6 months. Stable QFS was made by incorporating vitamin B12 in the solid iron premix at a 1:200 ratio. The process was scaled up to produce some 25 kg of iron and B12premix, sufficient for 5 tons of salt, or 500,000 daily doses of salt. Organoleptic testing of Indian meals produced with quadruple fortified salt were found to be acceptable by a consumer panel at the University of Delhi. Conclusions Stable quadruple fortified salt that can provide up to 50% of RDA of folic acid and iron and 100 + % of RDA of vitamin B12 and iodine has been developed. The product was pilot tested and had high consumer acceptability. The formulation could reduce the incidence of maternal and infant mortality at a cost of less than 20¢/annum. Funding Sources This research was funded by Grand Challenges Canada through the Saving Lives at Birth program, and by the Bill and Melinda Gates Foundation.

scholarly journals Maternal Characteristics Affect Fetal Growth Response to Maternal Supplements in the Women First Preconception Trial (WF) (P10-017-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Michael Hambidge ◽  
Carla Bann ◽  
Elizabeth McClure ◽  
Jamie Westcott ◽  
Ana Garces ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Maternal Nutrition ◽  
Secondary Analysis ◽  
Effect Modifier ◽  
Mixed Effect ◽  
Maternal Characteristics ◽  
Funding Sources ◽  
Effect Regression ◽  
Female Effect ◽  
Gates Foundation

Abstract Objectives Determine if maternal characteristics modified newborn anthropometric outcomes in the WF trial (ClinicalTrials.gov NCT01883193). Methods Secondary analysis included combined data for all 1465 maternal infant dyads in WF sites in Guatemala, India, and Pakistan who had 1st trimester ultrasounds and newborn anthropometry with the three WF arms maintained: Arm 1 commenced a comprehensive nutrition supplement ≥3 months prior to conception; Arm 2 commenced the same supplement in the 1st trimester, and Arm 3 received no trial supplements. Maternal characteristics included were: baseline, BMI, hemoglobin, age, education, SES, and parity plus newborn sex. Newborn outcomes were Z-scores for length (LAZ), weight (WAZ), and weight-to-length ratio (WLRZ). Mixed effect regression models were fit for each outcome, including treatment arm, effect modifier, and treatment arm x effect modifier interaction as predictors and controlling for study site, maternal characteristics, and newborn sex. Results Parity, anemia and newborn sex were significant effect modifiers favoring para 0 vs para ≥1, anemia vs non anemia, and newborn male vs female. Effect of Arm 1 vs 3 was significantly larger for para 0 vs ≥1 women on length and weight (Table). Arm 2 vs 3 was not associated with improvements for para 0 in weight (P = 0.273) or WLRZ (P = 0.710). Arms 1 and 2 (vs 3) were associated with significantly higher length, weight, and WLRZ for anemic women. For parity and anemia, effect sizes for Arm 1 were greater than for Arm 2 for WAZ and WLZ (P < 0.05), but not LAZ. Arm 1 and 2 were associated with significantly higher weight and WLRZ for male vs female newborn. Conclusions In diverse low resource populations, impaired fetal growth (weight and length) is substantially improved in nulliparous and in anemic women but minimally or not at all in parous and in non-anemic women. Correction of weight decrements is most pronounced with improvement in maternal nutrition commencing prior to conception. Funding Sources Bill & Melinda Gates Foundation; NIH, NICHD and ODS. Supporting Tables, Images and/or Graphs

scholarly journals Differences in the Fecal Metabolome and Microbiome Between Exclusive and Partial Breastfed Infants are More Pronounced at 2 Months Compared to 5 Months

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1097-1097 ◽  
Author(s):  
Aidong Wang ◽  
Aly Diana ◽  
Sofa Rahmannia ◽  
Rosalind Gibson ◽  
Lisa Houghton ◽  
...  
Keyword(s):  
Exclusive Breastfeeding ◽  
Feeding Practices ◽  
Illumina Miseq ◽  
Short Chain Fatty Acids ◽  
P Value ◽  
Fecal Samples ◽  
Breastfed Infants ◽  
Funding Sources ◽  
Gates Foundation ◽  
The Impact

Abstract Objectives This study aimed to characterize the impact of feeding practices on the infant fecal metabolome and microbiome at 2 months and 5 months of age in exclusive breastfeeding (EBF) and partial breastfeeding (PBF) infants. Methods Fecal samples were collected from infants at 2 months and 5 months of age from Bandung, Indonesia. Exclusive breastfeeding was determined using the stable isotope deuterium dose-to-mother (DTM) technique. Fecal metabolites were extracted using Dulbecco's phosphate-buffered saline, and analyzed using NMR spectroscopy. Fecal microbial DNA was extracted at the same time using the MoBio PowerLyzer PowerSoil DNA isolation kit (MoBio, Carlsbad, CA). The V4 region of 16SrRNA was targeted. The DNA library sample was analyzed via 300-bp paired-end sequencing on the Illumina MiSeq platform. Results Fecal samples from EBF infants at 2 months of age revealed significantly higher human milk oligosaccharides (HMOs), short-chain fatty acids and related metabolites compared to PBF infants. However, fecal samples from infants at 5 months of age revealed no differences in metabolome between EBF and PBF after p-value adjustment for multiple comparisons. Gut microbes, especially Bifidobacterium were higher in EBF infants at age 2 months even though not statistically significant. However, this difference was eliminated at age 5 months. Conclusions In the present study, infant feeding practices had a stronger influence on the infant fecal metabolome and microbiome at the age of 2 months as compared to 5 months. Funding Sources 2014 Bill & Melinda Gates Foundation. CS would also like to acknowledge funding from the Kinsella endowed chair in Food, Nutrition, and health as well as USDA-NIFA Hatch project 1,021,411.

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