TY - JOUR
T1 - Human milk oligosaccharides protect against the development of autoimmune diabetes in NOD-mice
AU - Xiao, Ling
AU - Van't Land, Belinda
AU - Engen, Phillip A.
AU - Naqib, Ankur
AU - Green, Stefan J.
AU - Nato, Angie
AU - Leusink-Muis, Thea
AU - Garssen, Johan
AU - Keshavarzian, Ali
AU - Stahl, Bernd
AU - Folkerts, Gert
N1 - Funding Information:
The authors gratefully acknowledge A. P. Vos for support in design and planning of the animal experiment and interpretation of the outcomes. The DNA Services Facility, Research Resources Center, University of Illinois at Chicago, Chicago, IL USA for bioinformatics analysis, J. Bastiaans, E. Voogt and N. Kettelarij for technical assistance (Nutricia Research, Utrecht, The Netherlands), H. Avezaat and Y van Dreumel (Animal Facility, Utrecht, The Netherlands) for their technical support.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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 human milk are therefore thought to be vital in the protection of children at risk for T1D, supporting immune and gut microbiota development in early life.
AB - 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 human milk are therefore thought to be vital in the protection of children at risk for T1D, supporting immune and gut microbiota development in early life.
UR - http://www.scopus.com/inward/record.url?scp=85042777021&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-22052-y
DO - 10.1038/s41598-018-22052-y
M3 - Article
C2 - 29497108
AN - SCOPUS:85042777021
SN - 2045-2322
VL - 8
SP - 1
EP - 15
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 3829
ER -