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Milk Fat Globule Membrane Supplementation in Formula Modulates the Neonatal Gut Microbiome and Normalizes Intestinal Development.

ABSTRACT: Breast milk has many beneficial properties and unusual characteristics including a unique fat component, termed milk fat globule membrane (MFGM). While breast milk yields important developmental benefits, there are situations where it is unavailable resulting in a need for formula feeding. Most formulas do not contain MFGM, but derive their lipids from vegetable sources, which differ greatly in size and composition. Here we tested the effects of MFGM supplementation on intestinal development and the microbiome as well as its potential to protect against Clostridium difficile induced colitis. The pup-in-a-cup model was used to deliver either control or MFGM supplemented formula to rats from 5 to 15 days of age; with mother's milk (MM) reared animals used as controls. While CTL formula yielded significant deficits in intestinal development as compared to MM littermates, addition of MFGM to formula restored intestinal growth, Paneth and goblet cell numbers, and tight junction protein patterns to that of MM pups. Moreover, the gut microbiota of MFGM and MM pups displayed greater similarities than CTL, and proved protective against C. difficile toxin induced inflammation. Our study thus demonstrates that addition of MFGM to formula promotes development of the intestinal epithelium and microbiome and protects against inflammation.

SUBMITTER: Bhinder G

PROVIDER: S-EPMC5368573 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Milk Fat Globule Membrane Supplementation in Formula Modulates the Neonatal Gut Microbiome and Normalizes Intestinal Development.

Bhinder Ganive G Allaire Joannie M JM Garcia Cyrielle C Lau Jennifer T JT Chan Justin M JM Ryz Natasha R NR Bosman Else S ES Graef Franziska A FA Crowley Shauna M SM Celiberto Larissa S LS Berkmann Julia C JC Dyer Roger A RA Jacobson Kevan K Surette Michael G MG Innis Sheila M SM Vallance Bruce A BA

Scientific reports 20170328

Breast milk has many beneficial properties and unusual characteristics including a unique fat component, termed milk fat globule membrane (MFGM). While breast milk yields important developmental benefits, there are situations where it is unavailable resulting in a need for formula feeding. Most formulas do not contain MFGM, but derive their lipids from vegetable sources, which differ greatly in size and composition. Here we tested the effects of MFGM supplementation on intestinal development and ...[more]

PMID: 28349941

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Project description:Milk fat globule membrane (MFGM), mainly comprising protein and fat, has been reported to have multiple biological functions for relieving intestinal inflammation and enhancing growth performance. We hypothesized that MFGM supplementation into sows' diet during late gestation can have a positive impact on the intestinal microecology of sows and their piglets, as well as on the growth of neonates. Therefore, the present study was conducted to investigate such effects and their potential mechanisms. Twenty-two pregnant sows were selected and randomly divided into the CON group (basal diet) and MFGM group (basal diet supplemented with 9.9 g per day MFGM). The feeding period began from d 85 of gestation and until farrowing. The concentrations of albumin (ALB), low-density lipoprotein cholesterol (LDL-C), and non-esterified fatty acids (NEFA) in plasma and short-chain fatty acids (SCFAs) in feces of sows from the MFGM group were determined. The concentrations of growth hormone (GH), immunoglobulin A (IgA), glucose (GLU), and NEFA in the umbilical cord blood in the MFGM group were significantly higher than those in the CON group. Piglets from the MFGM group showed improved growth performance, increased villus height in the jejunum, decreased crypt depth in the duodenum and jejunum, upregulated mRNA expressions of tight junctions (namely, Occludin; Claudin-1, Claudin-2, and Claudin-4; zonulin-1 (ZO-1)); mucins such as Mucin 2, Mucin 4, Mucin 13, and Mucin 20; and immune-related genes, such as tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-22 (IL-22), toll-like receptor 2 (TLR2), and toll-like receptor 4 (TLR4). In addition, the abundance of Prevotella in the feces of sows at farrowing and the abundance of Christensenellaceae_R-7_group in the feces of 21 day-old piglets from the MFGM group were significantly higher. Further correlation analysis revealed that the Christensenellaceae_R-7_group was positively correlated with the relative mRNA expressions of Occludin, Claudin-1, Claudin-2, Claudin-4, Mucin 13, TLR2, and TLR4. In conclusion, MFGM supplementation during late gestation improved the physiological status of sows by improving their plasma parameters and intestinal microecology. The improved provision of nutrients through the umbilical cord blood and optimized microbiota colonization in neonatal piglets were beneficial to the intestinal morphological structure and barrier functions, consequently improving the growth performance of neonates during lactation. These findings provide insights into the future applications of MFGM with regard to maternal-fetal nutrition and a new option for nutritional intervention of neonates through maternal dietary manipulation.

Project description:Impaired intestinal mucosal integrity and immunity are frequently observed in low-birth-weight (LBW) animals, which lead to inadequate growth and high neonatal mortality. However, the mechanisms of intestinal dysfunction in LBW animals are still unclear. Milk fat globule membrane (MFGM), a protein-lipid complex surrounding the fat globules in milk, has many healthful benefits for animals. Therefore, this study was conducted to explore the effect of MFGM supplementation on intestinal injury and inflammation in LBW mouse pups while being challenged with lipopolysaccharide (LPS). C57BL/6J LBW female neonatal mice were fed on breast milk and divided into four groups, including two normal diet groups (ND; CON group and LPS group) and the diet supplemented with two dosages of MFGM, namely, MFGM100 (ND plus MFGM at 100 mg/kg BW) and MFGM200 (ND plus MFGM at 200 mg/kg BW) from postnatal day (PND) 4 to PND 21. At PND21, pups from the LPS group, MFGM100 group, and MFGM200 group were injected intraperitoneally with LPS while the pups from the CON group were injected with equivalent volume of sterile saline. After 4 h of LPS administration, all pups were slaughtered and then the plasma, mid-ileum, and mid-colon tissue samples were collected. Our results showed that MFGM supplementation promoted the body weight from PND16 to PND21 and attenuated intestinal inflammation manifested by reduced histological damage, decreased secretion of TNF-α, IL-6, IFN-γ, and IL-1β, and improved oxidative stress characterized by increased SOD activity and decreased secretion of MDA. Expression of tight junction proteins (ZO-1, occludin, and claudin-1), MUC1, and MUC2 was increased in MFGM presupplemented groups compared to the LPS-challenged mice with normal diet. Meanwhile, the expression of proinflammatory cytokines and TLRs was decreased by MFGM presupplementation. Collectively, MFGM is a critical nutrient with an ability to improve the growth performance of LBW mouse pups, especially during the LPS challenge, by promoting the intestinal epithelial integrity and inhibiting inflammation through activating of TLR2 and TLR4 signals.

Project description:Exposure to adverse events in early life increases the risk of chronic metabolic disease in adulthood. The objective of this study was to determine the significance of milk fat globule membrane (MFGM)-mediated alterations in the gut microbiome to the metabolic health of offspring in the long-term. Female C57BL/6 mice were fed either a high-fat diet (HFD) or a control diet for 3 weeks before pregnancy and throughout pregnancy and lactation. During lactation, pups from the HFD group were breast-fed with or without 1,000 mg/kg BW/day MFGM supplementation (HFD and HFD-MS group, respectively). After weaning, the offspring in each group were divided into male and female subgroups. The weaned mice were then shifted to a control diet for 8 weeks. At the eleventh week, stool samples were collected for 16S rRNA gene sequencing. Serum biochemical parameters were analyzed, and intraperitoneal glucose and insulin tolerance tests were performed. Neonatal supplementation with MFGM ameliorated metabolic disorder and improved glucose tolerance in offspring exposed to maternal HFD in a sex-specific manner. Furthermore, maternal HFD induced gut microbiota perturbation in offspring in adulthood. Neonatal MFGM supplementation significantly enriched g-Parabacteroides, g-Bifidobacterium, g-Faecalibaculum, and g-Lactobacillus in male offspring exposed to maternal HFD, while significantly enriched g-Parabacteroides and g-Alistipes in female offspring exposed to maternal HFD. These bacteria may be associated with the favorable changes in metabolism that occur in adulthood. Sex differences in the changes of metagenomic pathways related to oxidative phosphorylation, citrate cycle, electron transfer carries, and ubiquinone biosynthesis were also observed in the offspring. Maternal HFD has an adverse effect on the metabolism of offspring in later life. Neonatal MFGM supplementation could modulate the structure of gut microbiota communities and may have long-term protective effects on lipid and glucose metabolism, but these effects are sex dimorphic.

Dataset Information

Milk Fat Globule Membrane Supplementation in Formula Modulates the Neonatal Gut Microbiome and Normalizes Intestinal Development.

Publications

Milk Fat Globule Membrane Supplementation in Formula Modulates the Neonatal Gut Microbiome and Normalizes Intestinal Development.

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