Notes

Milk Components Growth Components Milk Oligosaccharides Immunoglobulins Development
In an attempt to encourage the formation of a healthy gut microbiome comparable to that of a breastfed infant, manufacturers often supplement infant formula with prebiotics or probiotics, which are known to have a bifidogenic effect and can modulate the immune system. This review aims to elucidate the roles of human milk and formula milk on infants' gut and health.Conflict of interest statement The authors declare no conflict of interest.Novel Genes and Metabolite Trends in Bifidobacterium longum subsp. infantis Bi-26 Metabolism of Human Milk Oligosaccharide 2'-fucosyllactose.Zabel B(1), Yde CC(2), Roos P(3), Marcussen J(2), Jensen HM(2), Salli K(4), Human milk oligosaccharides (HMOs) function as prebiotics for beneficial bacteria in the developing gut, often dominated by Bifidobacterium spp.

To understand the relationship between bifidobacteria utilizing HMOs and how the metabolites that are produced could affect the host, we analyzed the metabolism of HMO 2'-fucosyllactose (2'-FL) in Bifidobacterium longum subsp. infantis Bi-26. RNA-seq and metabolite analysis (NMRGCMS) was performed on samples at early (A0 =5), mid-log ) and late-log phases (1-2) of growth. Transcriptomic analysis revealed many gene clusters including three novel ABC-type sugar transport clusters to be upregulated in Bi-26 involved in processing of 2'-FL along with metabolism of its monomers glucose, fucose and galactose. Metabolite data confirmed the production of formate, acetate, 1,2-propanediol, lactate and cleaving of fucose from 2'-FL. The formation of acetate, formate, and lactate showed how the cell uses metabolites during fermentation to produce higher levels of ATP (mid-log compared to other stages) or generate cofactors to balance redox. We concluded that 2'-FL metabolism is a complex process involving multiple gene clusters, that produce a more diverse metabolite profile compared to lactose.

These results provide valuable insight on the mode-of-action of 2'-FL utilization by Bifidobacterium longum subsp. Conflict of interest statement B.Z., C.C.Y., P.

R., W.M., J.M., H.M.

J., K.S., J.H. and A.C.

O. are all employees of DuPont, which manufactures and sells Bifidobacterium longum subsp. infantis Bi-26 and 2′-FL. Funding was provided by DuPont Nutrition & Health. The authors declare no non-financial competing A Novel Role for Necroptosis in the Pathogenesis of Necrotizing Enterocolitis.Werts AD(1), Fulton WB(2), Ladd MR(2), Saad-Eldin A(2), Chen YX(2), Kovler ML(2), Jia H(2), Banfield EC(3), Buck RH(4), Goehring K(4), Prindle T Jr(2), University School of Medicine, Baltimore, Maryland.University School of Medicine, Baltimore, Maryland.

School of Medicine, Baltimore, Maryland.University School of Medicine, Baltimore, Maryland; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Cell Mol Gastroenterol Hepatol. ;9(3)549-5.BACKGROUND & AIMS Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by Toll-like receptor 4 (TLR4)-dependent intestinal inflammation and enterocyte death. Given that necroptosis is a proinflammatory cell death process that is linked to bacterial signaling, we investigated its potential role in NEC, and the mechanisms involved.METHODS Human and mouse NEC intestine were analyzed for necroptosis gene expression (ie, RIPK1, RIPK3, and MLKL), and protein activation (phosphorylated RIPK3). To evaluate a potential role for necroptosis in NEC, the effects of genetic (ie, Ripk3 knockout or Mlkl knockout) or pharmacologic (ie, Nec1s) inhibition of intestinal inflammation were assessed in a mouse NEC model, and a possible upstream role of TLR4 was assessed in Tlr4-deficient mice.

The NEC-protective effects of human breast milk and its constituent milk oligosaccharides on necroptosis were assessed in a NEC-in-a-dish model, in which mouse intestinal organoids were cultured as either undifferentiated or differentiated epithelium in the presence of NEC bacteria and hypoxia.RESULTS Necroptosis was activated in the intestines of human and mouse NEC in a TLR4-dependent manner, and was up-regulated specifically in differentiated epithelium of the immature ileum. Inhibition of necroptosis genetically and pharmacologically reduced intestinal-epithelial cell death and mucosal inflammation in experimental NEC, and ex vivo in the NEC-in-a-dish system. Strikingly, the addition of human breast milk, or the human milk oligosaccharide 2 fucosyllactose in the ex vivo system, reduced necroptosis and inflammation.
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