Human milk oligosaccharides protect against the development of autoimmune diabetes in NOD-mice

Scientific Reports
Ling XiaoGert Folkerts

Abstract

Development of Type 1 diabetes (T1D) is influenced by non-genetic factors, such as optimal microbiome development during early life that "programs" the immune system. Exclusive and prolonged breastfeeding is an independent protective factor against the development of T1D, likely via bioactive components. Human Milk Oligosaccharides (HMOS) are microbiota modulators, known to regulate immune responses directly. Here we show that early life provision (only for a period of six weeks) of 1% authentic HMOS (consisting of both long-chain, as well as short-chain structures), delayed and suppressed T1D development in non-obese diabetic mice and reduced development of severe pancreatic insulitis in later life. These protective effects were associated with i) beneficial alterations in fecal microbiota composition, ii) anti-inflammatory microbiota-generating metabolite (i.e. short chain fatty acids (SCFAs)) changes in fecal, as well as cecum content, and iii) induction of anti-diabetogenic cytokine profiles. Moreover, in vitro HMOS combined with SCFAs induced development of tolerogenic dendritic cells (tDCs), priming of functional regulatory T cells, which support the protective effects detected in vivo. In conclusion, HMOS present in huma...Continue Reading

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Citations

Mar 23, 2019·European Journal of Immunology·Ling XiaoBelinda Van't Land
Mar 14, 2019·Journal of Diabetes·Ahmed M Abdellatif, Nora E Sarvetnick
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Datasets Mentioned

BETA
PRJNA362610
GM-CSF

Methods Mentioned

BETA
amplicon sequencing
NMR
flow cytometry
Assay
FACS

Software Mentioned

R
vegan
QIIME
uclust
PICRUSt ( Phylogenetic Investigation of Communities by Reconst...
SPSS
PICRUSt
FACS Diva
KEGG Mapper
FACS

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