Milk Formula Diet Alters Bacterial and Host Protein Profile in Comparison to Human Milk Diet in Neonatal Piglet Model.
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SUBMITTER: Rosa F
PROVIDER: S-EPMC8618976 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNeonatal diet has a large influence on child health and might modulate changes in fecal microbiota and metabolites.ObjectivesThe aim is to investigate fecal microbiota and metabolites at different ages in infants who were breastfed (BF), received dairy-based milk formula (MF), or received soy-based formula (SF).MethodsFecal samples were collected at 3 (n = 16, 12, and 14, respectively), 6 (n = 20, 19, and 15, respectively), 9 (n = 12, 11, and 12, respectively), and 12 mo (n = 14, 14, and 15, respectively) for BF, MF, and SF infants. Infants that breastfed until 9 mo and switched to formula were considered as no longer breastfeeding at 12 mo. Microbiota data were obtained using 16S ribosomal RNA sequencing. Untargeted metabolomics was conducted using a Q-Exactive Hybrid Quadrupole-Orbitrap mass spectrometer. The data were analyzed using R (version 3.6.0) within the RStudio (version 1.1.463) platform.ResultsAt 3, 6, and 9 mo of age BF infants had the lowest α-diversity, SF infants had the highest diversity, and MF was intermediate. Bifidobacterium was 2.6- to 5-fold lower in SF relative to BF infants through 1 y of life. An unidentified genus from Ruminococcaceae higher in the SF (2%) than in the MF (0.4%) and BF (0.08%) infants at 3 mo of age was observed. In BF infants higher levels of butyric acid, d-sphingosine, kynurenic acid, indole-3-lactic acid, indole-3-acetic acid, and betaine were observed than in MF and SF infants. At 3 mo Ruminococcaceae was positively correlated to azelaic, gentisic, isocitric, sebacic, and syringic acids. At 6 mo Oscillospira was negatively correlated with 3-hydroxybutyric-acid, hydroxy-hydrocinnamic acid, and betaine whereas Bifidobacterium was negatively associated with 5-hydroxytryptamine. At 12 mo of age, Lachnospiraceae was negatively associated with hydroxyphenyllactic acid.ConclusionsInfant diet has a large impact on the fecal microbiome and metabolome in the first year of life.This study was registered at clinicaltrials.gov as NCT00616395.
| S-EPMC7266684 | biostudies-literature
Project description:Background:Neonatal diet impacts many physiological systems and can modify risk for developing metabolic disease and obesity later in life. Less well studied is the effect of postnatal diet (e.g., comparing human milk (HM) or milk formula (MF) feeding) on mitochondrial bioenergetics. Such effects may be most profound in splanchnic tissues that would have early exposure to diet-associated or gut microbe-derived factors. Methods:To address this question, we measured ileal and liver mitochondrial bioenergetics phenotypes in male piglets fed with HM or MF from day 2 to day 21 age. Ileal and liver tissue were processed for mitochondrial respiration (substrate only [pyruvate, malate, glutamate], substrate + ADP, and proton "leak" post-oligomycin; measured by Oroboros methods), mitochondrial DNA (mtDNA) and metabolically-relevant gene expression analyses. Results:No differences between the diet groups were observed in mitochondrial bioenergetics indices in ileal tissue. In contrast, ADP-dependent liver Complex I-linked OXPHOS capacity and Complex I?+?II-linked OXPHOS capacity were significantly higher in MF animals relative to HM fed piglets. Interestingly, p53, Trap1, and Ppar? transcript abundances were higher in MF-fed relative to HM-fed piglets in the liver. Mitochondrial DNA copy numbers (normalized to nuclear DNA) were similar within-tissue regardless of postnatal diet, and were ~?2-3 times higher in liver vs. ileal tissue. Conclusion:While mechanisms remain to be identified, the data indicate that neonatal diet can significantly impact liver mitochondrial bioenergetics phenotypes, even in the absence of a change in mtDNA abundance. Since permeabilized liver mitochondrial respiration was increased in MF piglets only in the presence of ADP, it suggests that formula feeding led to a higher ATP turnover. Specific mechanisms and signals involved with neonatal diet-associated differences in liver bioenergetics remain to be elucidated.
| S-EPMC7158137 | biostudies-literature
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.
| S-EPMC6888031 | biostudies-literature
Project description:Early nutrition plays a dominant role in infant development and health. It is now understood that the infant diet impacts the gut microbiota and its relationship with gut function and brain development. However, its impact on the microbiota-gut-brain axis has not been studied in an integrative way. The objective here was to evaluate the effects of human milk (HM) or cow's milk based infant formula (IF) on the relationships between gut microbiota and the collective host intestinal-brain axis. Eighteen 10-day-old Yucatan mini-piglets were fed with HM or IF. Intestinal and fecal microbiota composition, intestinal phenotypic parameters, and the expression of genes involved in several gut and brain functions were determined. Unidimensional analyses were performed, followed by multifactorial analyses to evaluate the relationships among all the variables across the microbiota-gut-brain axis. Compared to IF, HM decreased the α-diversity of colonic and fecal microbiota and modified their composition. Piglets fed HM had a significantly higher ileal and colonic paracellular permeability assessed by ex vivo analysis, a lower expression of genes encoding tight junction proteins, and a higher expression of genes encoding pro-inflammatory and anti-inflammatory immune activity. In addition, the expression of genes involved in endocrine function, tryptophan metabolism and nutrient transport was modified mostly in the colon. These diet-induced intestinal modifications were associated with changes in the brain tissue expression of genes encoding the blood-brain barrier, endocrine function and short chain fatty acid receptors, mostly in hypothalamic and striatal areas. The integrative approach underlined specific groups of bacteria (Veillonellaceae, Enterobacteriaceae, Lachnospiraceae, Rikenellaceae, and Prevotellaceae) associated with changes in the gut-brain axis. There is a clear influence of the infant diet, even over a short dietary intervention period, on establishment of the microbiota-gut-brain axis.
| S-EPMC9532976 | biostudies-literature
Project description:BackgroundSialyllactose (SL) is a highly abundant oligosaccharide in human milk that has been shown to influence intestinal maturation and cognitive development and exert bifidogenic effects on the gut microbiota. The SL content of infant formula is significantly less than that of human milk, therefore there is interest in determining the effect of supplementing SL to infant formula at the levels in human milk on neonatal outcomes.ObjectiveThe aim of this study was to investigate the effect of varying doses of dietary SL compared with a milk replacer formula on weight gain, gastrointestinal development, and microbiota composition in piglets.MethodsThirty-eight intact male piglets were randomly assigned to 1 of 4 experimental diets from 2 to 32-33 d of age. Diets were formulated to contain SL at 0 mg/L (CON), 130 mg/L (LOW), 380 mg/L (MOD), or 760 mg/L (HIGH). At 32-33 d of age, blood was collected for serum chemistry and blood cellular analyses, and coagulation time. Immediately after humane killing, the small intestine was excised and intestinal segments fixed for quantification of mucin-producing goblet cells and morphologic analysis. In addition, mucosal disaccharide activity was assessed. Colonic luminal contents and feces were collected for measurement of pH, dry matter, volatile fatty acids, and the microbiota.ResultsSL at ≤760 mg/L supported normal growth, intestinal development, and enzyme activity as well as serum chemistries and hematology (P > 0.05). In addition, SL supplementation did not affect overall microbiota structure and diversity in ascending colon contents and feces, but had minor effects on the relative abundances of specific microbes.ConclusionsThe findings in this study demonstrate that SL addition to a prebiotic-containing formula was well-tolerated by neonatal piglets, supported normal growth, and did not result in any adverse effects on serum chemistries or intestinal development.
| S-EPMC6226774 | biostudies-literature
Project description:Postnatal dietary modulation of microRNAs (miRNAs) and effects on miRNA-mRNA interactions in tissues remain unknown. This study aimed to investigate whether dietary factors (formula vs. breastfeeding) affect mammary miRNA expression and to determine if these changes are concurrent with developmental alterations of the mammary gland in neonatal piglets. Female Yorkshire/Duroc piglets were fed sow's milk or cow's milk- or soy-based infant formula (from postnatal day 2 to day 21; n=6/group). Differentially expressed miRNAs were determined using mammary miRNA profiling, followed by miRNA and mRNA expressions characterized by quantitative reverse-transcription polymerase chain reaction. Milk and soy formulas reduced expressions of miR-1, -128, -133a, -193b, -206 and -27a; miRNA down-regulation altered mRNA expressions of genes (e.g., Ccnd1, Tgfb3, Igf1r and Tbx3) that were consistent with enhanced cell proliferation and suppressed apoptotic processes in the developing mammary gland. Interestingly, down-regulation of miR-1, -128 and -27a also correlated with increased mRNA genes such as Hmgcs and Hmgcr encoding cholesterol synthesis in the mammary glands in response to lower circulating cholesterol levels. Infant formula feeding affected mammary miRNA profiles in neonatal piglets, concurrent with increased expression of cell proliferation and cholesterol synthesis genes, suggesting early nutritional modulation of miRNAs may contribute to regulation of proliferative status and cholesterol homeostasis of developing mammary glands during infancy.
| S-EPMC8208835 | biostudies-literature
Project description:The benefits of breastfeeding infants are well characterized, including those on the immune system. However, determining the mechanism by which human breast milk (HBM) elicits effects on immune response requires investigation in an appropriate animal model. In the current study we used neonatal piglets and compared their gut microbiome using mass spectrometry based metaproteomics
2021-11-03 | PXD025432 | Pride
Project description:Formula-fed infants present higher cholesterol synthesis rates and lower circulating cholesterol during the postnatal feeding period compared to breast-fed infants, though the mechanisms underlying this phenotype are not fully understood. Typical infant formulas contain vegetable-based fats, inherently including phytosterols (PS), which are structurally similar to cholesterol and may interfere with their absorption. A seven-day old piglets model was used to test the inhibitory effects of PS on cholesterol absorption during postnatal feeding. Following feeding for 21 days with milk-based formulas containing PS and cholesterol levels resembling those in formulas or human-milk, apparent cholesterol digestibility was analyzed in ileal digesta, and cholesterol, PS, and cholesterol synthesis markers were analyzed in plasma and liver samples. Ileal cholesterol digestibility content was increased in the piglets fed low PS formulas and the rate of the hepatic cholesterol synthesis, as determined by the lathosterol-to-cholesterol ratios (L:C), was decreased in the piglets fed LP-formulas and corresponded to reduced nuclear expression of SREBP2 relative to those fed HP-formulas. These results are consistent with the hypothesis that PS in formula can inhibit cholesterol absorption and enhance cholesterol synthesis. Whether or not this leads to entrainment of cholesterol synthesis later in life via early programming awaits further research.
| S-EPMC6316586 | biostudies-literature
Project description:The impact of human milk (HM) or dairy milk-based formula (MF) on the large intestine's metabolome was not investigated. Two-day old male piglets were randomly assigned to HM or MF diet (n = 26/group), from postnatal day (PND) 2 through 21 and weaned to a solid diet until PND 51. Piglets were euthanized at PND 21 and PND 51, luminal contents of the cecum, proximal (PC) and distal colons (DC), and rectum were collected and subjected to metabolomics analysis. Data analyses were performed using Metaboanalyst. In comparison to MF, the HM diet resulted in higher levels of fatty acids in the lumen of the cecum, PC, DC, and rectum at PND 21. Glutamic acid was greater in the lumen of cecum, PC, and DC relative to the MF group at PND 21. Also, spermidine was higher in the DC and rectal contents of HM relative to MF at PND 21. MF diet resulted in greater abundances of amino acids in the cecal lumen relative to HM diet at PND 21. Additionally, several sugar metabolites were higher in various regions of the distal gut of MF fed piglets relative to HM group at PND 21. In contrast, at PND 51, in various regions there were higher levels of erythritol, maltotriose, isomaltose in HM versus MF fed piglets. This suggests a post weaning shift in sugar metabolism that is impacted by neonatal diet. The data also suggest that infant diet type and host-microbiota interactions likely influence the lower gut metabolome.
| S-EPMC7750455 | biostudies-literature
Project description:BackgroundSoy infant formula contains isoflavones, which are able to bind to and activate estrogen receptor (ER) pathways. The mammary gland is sensitive to estrogens, raising concern that the use of soy formulas may promote premature development.ObjectiveWe aimed to determine if soy formula feeding increases mammary gland proliferation and differentiation in comparison to other infant postnatal diets.MethodsWhite-Dutch Landrace piglets aged 2 d received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17-beta-estradiol (2 mg/(kg·d); M + E2), or milk formula supplemented with genistein (84 mg/L of diet; M + G) until day 21. Mammary gland proliferation and differentiation was assessed by histology, and real-time RT-PCR confirmation of differentially expressed genes identified by microarray analysis.ResultsMammary terminal end bud numbers were 19-31% greater in the Milk, Soy, and M + G groups relative to the Sow and M + E2, P <0.05. Microarray analysis identified differentially expressed genes between each formula-fed group relative to the Sow (±1.7-fold, P <0.05). Real-time RT-PCR confirmed 2- to 4-fold increases in mRNA transcripts of genes involved in cell proliferation, insulin-like growth factor 1 (IGF1), fibroblast growth factor 10 (FGF10), and fibroblast growth factor 18 (FGF18), in all groups relative to the Sow, P <0.05. In contrast, genes involved in cell differentiation and ductal morphogenesis, angiotensin II receptor type 2 (AGTR2), microtubule associated protein 1b (MAP1B), and kinesin family member 26b (KIF26B), were significantly upregulated by 2-, 4-, and 13-fold, respectively, in the M + E2 group. Additionally, mRNA expression of ER-specific gene targets, progesterone receptor (PGR), was increased by 12-fold, and amphiregulin (AREG) and Ras-like estrogen regulated growth inhibitor (RERG) expression by 1.5-fold in the M + E2 group, P <0.05. In the soy and M + G groups, mRNA expressions of fatty acid synthesis genes were increased 2- to 4-fold.ConclusionsOur data indicate soy formula feeding does not promote ER-signaling in the piglet mammary gland. Infant formula feeding (milk- or soy-based) may initiate proliferative pathways independently of estrogenic signaling.
| S-EPMC7138673 | biostudies-literature