Knowledge-Formula-Milk-Simulate-Effects-Breast-Milk-e

Human Milk Oligosaccharides in Maternal Serum Respond to Oral Glucose Load and Are Associated with Insulin Sensitivity.Weiser-Fuchs MT(1)(2), Maggauer E(1), van Poppel MNM(3)(4), Csapo B(1), Desoye G(1)(2), Köfeler HC(4)(5), Groselj-Strele A(6), Trajanoski S(6), Fluhr H(1)(2), Obermayer-Pietsch B(7)(8), Jantscher-Krenn E(1)(2)(4).University of Graz, 36 Graz, Austria.Medical University of Graz, 36 Graz, Austria.Medical University of Graz, 36 Graz, Austria.suboptimal adaptations can lead to gestational diabetes mellitus (GDM).

Human milk oligosaccharides (HMOs) circulate in maternal blood in pregnancy and are altered with GDM, suggesting influence of glucose homeostasis on HMOs. Lactose-N-neotetraose assessed the HMO response to glucose load during an oral glucose tolerance test sensitivity in healthy pregnant women. (2) Methods Serum of 99 women, collected at h, 1 h and 2 h during a 75 g OGTT at 24-28 gestational weeks was analyzed for HMOs (2'FL, 3'SLN, LDFT, 3'SL) by HPLC; plasma glucose, insulin and C-peptide were analyzed by standard biochemistry methods. (3) Results Serum 3'SL concentrations significantly increased from fasting to 1 h after glucose load, while concentrations of the other HMOs were unaltered. Higher 3'SL at all OGTT time points was associated with a generally more diabetogenic profile, with higher hepatic insulin resistance (HOMA-IR), lower insulin sensitivity (Matsuda index) and higher insulin secretion (C-peptide index 1). (4) Conclusions Rapid increase in serum 3'SL post-oral glucose load (fasted-fed transition) indicates utilization of plasma glucose, potentially for sialylation of lactose. Associations of sialylated HMOs with a more diabetogenic profile suggest sustained adaptations to impaired glucose homeostasis in pregnancy.

Underlying Fucosylated oligosaccharides or potential consequences of observed HMO changes remain to be Conflict of interest statement The authors declare no conflict of interest.The human milk oligosaccharide 2'-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation.He Y(1), Liu S(2), Kling DE(3), Leone S(3), Lawlor NT(3), Huang Y(3), Feinberg Harvard Medical School, Charlestown, Massachusetts, USA Program in Glycobiology, Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA.Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, BACKGROUND A major cause of enteric infection, Gram-negative pathogenic bacteria activate mucosal inflammation through lipopolysaccharide (LPS) binding to intestinal toll-like receptor 4 (TLR4). Breast feeding lowers risk of disease, and human milk modulates inflammation.OBJECTIVE This study tested whether human milk oligosaccharides (HMOSs) influence pathogenic Escherichia coli-induced interleukin (IL)-8 release by intestinal epithelial cells (IECs), identified specific proinflammatory signalling molecules modulated by HMOSs, specified the active HMOS and METHODS Models of inflammation were IECs invaded by type 1 pili enterotoxigenic E. coli (ETEC) in vitro T84 modelled mature, and H4 modelled immature IECs.

LPS-induced signalling molecules co-varying with IL-8 release in the presence or absence of HMOSs were identified. Knockdown and overexpression verified signalling mediators. The oligosaccharide responsible for altered signalling was RESULTS HMOSs attenuated LPS-dependent induction of IL-8 caused by ETEC, uropathogenic E. coli, and adherent-invasive E. coli (AIEC) infection, and suppressed CD14 transcription and translation. CD14 knockdown recapitulated HMOS-induced attenuation. Overexpression of CD14 increased the inflammatory response to ETEC and sensitivity to inhibition by HMOSs.

2'-fucosyllactose suppress CD14 expression, and protected AIEC-infected mice.CONCLUSIONS HMOSs and 2'-FL directly inhibit LPS-mediated inflammation during ETEC invasion of T84 and H4 IECs through attenuation of CD14 induction. CD14 expression mediates LPS-TLR4 stimulation of portions of the 'macrophage migration inhibitory factors' inflammatory pathway via suppressors of cytokine signalling 2signal transducer and activator of transcription 3NF-κB. HMOS direct inhibition of inflammation supports its functioning as an innate immune system whereby the mother protects her vulnerable neonate through her milk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to httpwww.bmj.

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