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University of Groningen

Mom's sweet gift

Cheng, Lianghui

DOI:

10.33612/diss.127480932

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date: 2020

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Cheng, L. (2020). Mom's sweet gift: The beneficial effects of human milk oligosaccharides and their structure-function relationships. University of Groningen. https://doi.org/10.33612/diss.127480932

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Mom’s sweet gift

The beneficial effects of human milk oligosaccharides and their

structure-function relationships

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This research described in this thesis was financially supported by the China Scholarship Council and University Medical Center Gronigen.

Final support by the University of Groningen, University Medical Center Gronigen, and the Graduate School of Medical Sciences (GUIDE) for the printing of this thesis is greatfully acknowleadged.

Layout Lianghui Cheng Cover design W.Qin

Printed by Off page

Amsterdam, The Netherlands ISBN 978-94-034-2655-6 (print)

978-94-034-2654-9 (digital)

© Copyright 2020 Lianghui Cheng, Groningen, The Netherdands

All right reserved. No part of the thesis may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, without prior written permission of the authour.

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Mom’s sweet gift

The beneficial effects of human milk oligosaccharides and their

structure-function relationships

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on

Tuesday 23 June 2020 at 11.00 hours

by

Lianghui Cheng

born on 24 October 1991

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Supervisor

Prof. P. de Vos

Co-supervisor

Dr. M.M. Faas

Assessment Committee

Prof. G. Folkerts Prof. T. Plosch Prof. L. Dijkhuizen

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Table of contents

Chapter 1 More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects

9

Rationale and outline of the thesis 32

Chapter 2 Human milk oligosaccharides and its acid hydrolysate LNT2 show immunomodulatory effects via TLRs in a dose and structure-dependent way

39

Chapter 3 The human milk oligosaccharides 3-FL, LNnT, and LDFT attenuate TNF-α induced inflammation in fetal intestinal epithelial cells through shedding or interacting with TNF receptor 1

65

Chapter 4 Human milk oligosaccharides differently modulate goblet cells under homeostatic, proinflammatory conditions and under ER-stress

83

Chapter 5 Human milk oligosaccharides (hMOs) modulate the growth and fermentation of Bifidobacterium longum subsp. infantis in a hMO specific fashion in both monoculture and co-culture with Faecalibacterium prausnitzii

107

Chapter 6 Effects of human milk oligosaccharides on the crosstalk between commensal bacteria and intestinal epithelium in presence of intestinal peristaltic shear force

125

Chapter 7 General discussion 151 Appendices

Summary 164

Nederlandse samenvatting 168

Acknowledgments 172

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