Dataset Information

New generation lipid emulsions increase brain DHA and improve body composition, but not short-term neurodevelopment in parenterally-fed preterm piglets.

ABSTRACT: New generation, multicomponent parenteral lipid emulsions provide key fatty acids for brain growth and development, such as docosahexaenoic acid (DHA) and arachidonic acid (AA), yet the content may be suboptimal for preterm infants. Our aim was to test whether DHA and AA-enriched lipid emulsions would increase activity, growth, and neurodevelopment in preterm piglets and limit brain inflammation. Cesarean-delivered preterm pigs were given three weeks of either enteral preterm infant formula (ENT) or TPN with one of three parenteral lipid emulsions: Intralipid (IL), SMOFlipid (SMOF) or an experimental emulsion (EXP). Activity was continuously monitored and weekly blood sampling and behavioral field testing performed. At termination of the study, whole body and tissue metrics were collected. Neuronal density was assessed in sections of hippocampus (HC), thalamus, and cortex. Frontal cortex (FC) and HC tissue were assayed for fatty acid profiles and expression of genes of neuronal growth and inflammation. After 3?weeks of treatment, brain DHA content in SMOF, EXP and ENT pigs was higher (P?

SUBMITTER: Molina TL

PROVIDER: S-EPMC6813879 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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New generation lipid emulsions increase brain DHA and improve body composition, but not short-term neurodevelopment in parenterally-fed preterm piglets.

Molina Tiffany L TL Stoll Barbara B Mohammad Mahmoud M Mohila Carrie A CA Call Lee L Cui Liwei L Guthrie Gregory G Kunichoff Dennis D Lin Sen S Welch-Jernigan Rebecca R Nielsen Jon J Premkumar Muralidhar M Robinson Jason J Smith Victoria V Teets Haley H Obelitz-Ryom Karina K Hagan Joseph J Cruz Stephanie S Lau Patricio P Puyau Maurice M Shypailo Roman R Manjarin Rodrigo R Butte Nancy N Fang Zhengfeng Z Olutoye Oluyinka O Thymann Thomas T Sangild Per P Burrin Douglas D

Brain, behavior, and immunity 20190424

New generation, multicomponent parenteral lipid emulsions provide key fatty acids for brain growth and development, such as docosahexaenoic acid (DHA) and arachidonic acid (AA), yet the content may be suboptimal for preterm infants. Our aim was to test whether DHA and AA-enriched lipid emulsions would increase activity, growth, and neurodevelopment in preterm piglets and limit brain inflammation. Cesarean-delivered preterm pigs were given three weeks of either enteral preterm infant formula (ENT ...[more]

PMID: 31026499

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Project description:BACKGROUND:Early infant diet influences postnatal gut microbial development, which in turn can modulate the developing immune system. OBJECTIVES:The aim of this study was to characterize diet-specific bioregional microbiota differences in piglets fed either human breast milk (HM) or infant formula. METHODS:Male piglets (White Dutch Landrace Duroc) were raised on HM or cow milk formula (MF) from postnatal day (PND) 2 to PND 21 and weaned to an ad libitum diet until PND 51. Piglets were euthanized on either PND 21 or PND 51, and the gastrointestinal contents were collected for 16s RNA sequencing. Data were analyzed using the Quantitative Insight into Microbial Ecology. Diversity measurements (Chao1 and Shannon) and the Wald test were used to determine relative abundance. RESULTS:At PND 21, the ileal luminal region of HM-fed piglets showed lower Chao1 operational taxonomic unit diversity, while Shannon diversity was lower in cecal, proximal colon (PC), and distal colon (DC) luminal regions, relative to MF-fed piglets. In addition, at PND 51, the HM-fed piglets had lower genera diversity within the jejunum, ileum, PC, and DC luminal regions, relative to MF-fed piglets. At PND 21, Turicibacter was 4- to 5-fold lower in the HM-fed piglets' ileal, cecal, PC, and DC luminal regions, relative to the MF-fed piglets. Campylobacter is 3- to 6-fold higher in HM-fed piglets duodenal, ileal, cecal, PC, and DC luminal regions, in comparison to MF-fed piglets. Furthermore, the large intestine (cecum, PC, and rectum) luminal region of HM-fed piglets showed 4- to 7-fold higher genera that belong to class Bacteroidia, in comparison to MF-fed piglets at PND 21. In addition, at PND 51 distal colon lumen of HM-fed piglets showed 1.5-fold higher genera from class Bacteroidia than the MF-fed piglets. CONCLUSIONS:In the large intestinal regions (cecum, PC, and rectum), MF diet alters microbiota composition, relative to HM diet, with sustained effects after weaning from the neonatal diet. These microbiota changes could impact immune system and health outcomes later in life.

Project description:BackgroundEffects of diet on the structure and function of gut microbial communities in newborn infants are poorly understood. High-resolution molecular studies are needed to definitively ascertain whether gut microbial communities are distinct in milk-fed and formula-fed infants.Methodology/principal findingsPyrosequencing-based whole transcriptome shotgun sequencing (RNA-seq) was used to evaluate community wide gut microbial gene expression in 21 day old neonatal piglets fed either with sow's milk (mother fed, MF; n = 4) or with artificial formula (formula fed, FF; n = 4). Microbial DNA and RNA were harvested from cecal contents for each animal. cDNA libraries and 16S rDNA amplicons were sequenced on the Roche 454 GS-FLX Titanium system. Communities were similar at the level of phylum but were dissimilar at the level of genus; Prevotella was the dominant genus within MF samples and Bacteroides was most abundant within FF samples. Screened cDNA sequences were assigned functional annotations by the MG-RAST annotation pipeline and based upon best-BLASTX-hits to the NCBI COG database. Patterns of gene expression were very similar in MF and FF animals. All samples were enriched with transcripts encoding enzymes for carbohydrate and protein metabolism, as well as proteins involved in stress response, binding to host epithelium, and lipopolysaccharide metabolism. Carbohydrate utilization transcripts were generally similar in both groups. The abundance of enzymes involved in several pathways related to amino acid metabolism (e.g., arginine metabolism) and oxidative stress response differed in MF and FF animals.Conclusions/significanceAbundant transcripts identified in this study likely contribute to a core microbial metatranscriptome in the distal intestine. Although microbial community gene expression was generally similar in the cecal contents of MF and FF neonatal piglets, several differentially abundant gene clusters were identified. Further investigations of gut microbial gene expression will contribute to a better understanding of normal and abnormal enteric microbiology in animals and humans.

Project description:Preterm infants born with immature organ systems, which can impede normal development, can also be highly sensitive to different biological and/or environmental factors. Animal models could aid in investigating and understanding the effects of different conditions on the health of these immunocompromised infants. The epitheliochorial placentation of the pig prevents the prenatal transfer of protective colostral immunoglobulins. Surgical colostrum-deprived piglets are free of maternal immunoglobulins, and the cells that are normally provided via colostrum. We bred preterm germ-free piglets in sterile conditions and compared them with their term counterparts. Enterocyte development and intestinal morphology, tight junction proteins claudin-1 and occludin, pattern-recognizing receptors, adaptor molecules and coreceptors (RAGE, TLR2, TLR4, TLR9, MyD88, TRIF, MD2, and CD14), and inflammasome NLRP3 transcription were all evaluated. The production of inflammatory mediators IFN-α, IL-4, IL-6, IL-8, IL-10, IL-12/23 p40, TNF-α, IFN-γ, and high mobility group box 1 (HMGB1) in the intestine of germ-free piglets was also assessed. In the preterm germ-free piglets, the ileum showed decreased lamina propria cellularity, reduced villous height, and thinner and less distinct stratification - especially muscle layer, in comparison with their term counterparts. Claudin-1 transcription increased in the intestine of the preterm piglets. The transcription levels of pattern-recognizing receptors and adaptor molecules showed ambiguous trends between the groups. The levels of IL-6, IL-8, IL-10, and TNF-α were increased in the preterm ileum numerically (though not significantly), with statistically significant increases in the colon. Additionally, IL-12/23 p40 and IFN-γ were statistically significantly higher in the preterm colon. Both blood plasma and intestinal HMGB1 levels were nonsignificantly higher in the preterm group. We propose that the intestine of the preterm germ-free piglets showed "mild inflammation in sterile conditions." This model, which establishes preterm, hysterectomy-derived germ-free piglets, without protective maternal immunoglobulins, can be used to study influences of microbiota, nutrition, and therapeutic interventions on the development and health of vulnerable immunocompromised preterm infants.

Dataset Information

New generation lipid emulsions increase brain DHA and improve body composition, but not short-term neurodevelopment in parenterally-fed preterm piglets.

Publications

New generation lipid emulsions increase brain DHA and improve body composition, but not short-term neurodevelopment in parenterally-fed preterm piglets.

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