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Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt(+) Treg cell-mediated immune tolerance in neonates
Gestational diabetes mellitus (GDM) is an increasing public health concern that significantly increases the risk of early childhood allergic diseases. Altered maternal milk glycobiome may strongly affect gut microbiota and enteric-specific Treg cell-mediated development of immune tolerance in GDM in...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519364/ https://www.ncbi.nlm.nih.gov/pubmed/37741825 http://dx.doi.org/10.1080/19490976.2023.2256749 |
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author | Li, Xinke Ning, Xixi Rui, Binqi Wang, Yushuang Lei, Zengjie Yu, Da Liu, Feitong Deng, Yanjie Yuan, Jieli Li, Wenzhe Yan, Jingyu Li, Ming |
author_facet | Li, Xinke Ning, Xixi Rui, Binqi Wang, Yushuang Lei, Zengjie Yu, Da Liu, Feitong Deng, Yanjie Yuan, Jieli Li, Wenzhe Yan, Jingyu Li, Ming |
author_sort | Li, Xinke |
collection | PubMed |
description | Gestational diabetes mellitus (GDM) is an increasing public health concern that significantly increases the risk of early childhood allergic diseases. Altered maternal milk glycobiome may strongly affect gut microbiota and enteric-specific Treg cell-mediated development of immune tolerance in GDM infants. In this study, we found that, compared with healthy Chinese mothers, mothers with GDM had significantly lower levels of total and specific human milk oligosaccharides (HMOs) in their colostrum that subsequently increased with extension of lactation. This alteration in HMO profiles significantly delayed colonization of Lactobacillus and Bifidobacterium spp. in their breast-fed infants, resulting in a distinct gut microbial structure and metabolome. Further experiments in GDM mouse models indicated that decreased contents of milk oligosaccharides, mainly 3ʹ-sialyllactose (3ʹ-SL), in GDM maternal mice reduced colonization of bacteria, such as L. reuteri and L. johnsonii, in the neonatal gut, which impeded development of RORγt(+) regulatory T (Treg) cell-mediated immune tolerance. Treatment of GDM neonates with 3ʹ-SL, Lactobacillus reuteri (L. reuteri) and L. johnsonii promoted the proliferation of enteric Treg cells and expression of transcription factor RORγt, which may have contributed to compromising ovalbumin (OVA)-induced allergic responses. In vitro experiments showed that 3ʹ-SL, metabolites of L. johnsonii, and lysates of L. reuteri stimulated differentiation of mouse RORγt(+) Treg cells through multiple regulatory effects on Toll-like receptor, MAPK, p53, and NOD-like receptor signaling pathways. This study provides new ideas for the development of gut microbiota and immune tolerance in GDM newborns. |
format | Online Article Text |
id | pubmed-10519364 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-105193642023-09-26 Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt(+) Treg cell-mediated immune tolerance in neonates Li, Xinke Ning, Xixi Rui, Binqi Wang, Yushuang Lei, Zengjie Yu, Da Liu, Feitong Deng, Yanjie Yuan, Jieli Li, Wenzhe Yan, Jingyu Li, Ming Gut Microbes Research Paper Gestational diabetes mellitus (GDM) is an increasing public health concern that significantly increases the risk of early childhood allergic diseases. Altered maternal milk glycobiome may strongly affect gut microbiota and enteric-specific Treg cell-mediated development of immune tolerance in GDM infants. In this study, we found that, compared with healthy Chinese mothers, mothers with GDM had significantly lower levels of total and specific human milk oligosaccharides (HMOs) in their colostrum that subsequently increased with extension of lactation. This alteration in HMO profiles significantly delayed colonization of Lactobacillus and Bifidobacterium spp. in their breast-fed infants, resulting in a distinct gut microbial structure and metabolome. Further experiments in GDM mouse models indicated that decreased contents of milk oligosaccharides, mainly 3ʹ-sialyllactose (3ʹ-SL), in GDM maternal mice reduced colonization of bacteria, such as L. reuteri and L. johnsonii, in the neonatal gut, which impeded development of RORγt(+) regulatory T (Treg) cell-mediated immune tolerance. Treatment of GDM neonates with 3ʹ-SL, Lactobacillus reuteri (L. reuteri) and L. johnsonii promoted the proliferation of enteric Treg cells and expression of transcription factor RORγt, which may have contributed to compromising ovalbumin (OVA)-induced allergic responses. In vitro experiments showed that 3ʹ-SL, metabolites of L. johnsonii, and lysates of L. reuteri stimulated differentiation of mouse RORγt(+) Treg cells through multiple regulatory effects on Toll-like receptor, MAPK, p53, and NOD-like receptor signaling pathways. This study provides new ideas for the development of gut microbiota and immune tolerance in GDM newborns. Taylor & Francis 2023-09-23 /pmc/articles/PMC10519364/ /pubmed/37741825 http://dx.doi.org/10.1080/19490976.2023.2256749 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. |
spellingShingle | Research Paper Li, Xinke Ning, Xixi Rui, Binqi Wang, Yushuang Lei, Zengjie Yu, Da Liu, Feitong Deng, Yanjie Yuan, Jieli Li, Wenzhe Yan, Jingyu Li, Ming Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt(+) Treg cell-mediated immune tolerance in neonates |
title | Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt(+) Treg cell-mediated immune tolerance in neonates |
title_full | Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt(+) Treg cell-mediated immune tolerance in neonates |
title_fullStr | Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt(+) Treg cell-mediated immune tolerance in neonates |
title_full_unstemmed | Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt(+) Treg cell-mediated immune tolerance in neonates |
title_short | Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt(+) Treg cell-mediated immune tolerance in neonates |
title_sort | alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of rorγt(+) treg cell-mediated immune tolerance in neonates |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519364/ https://www.ncbi.nlm.nih.gov/pubmed/37741825 http://dx.doi.org/10.1080/19490976.2023.2256749 |
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