Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice

Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-α1,3-GlcNAc (3FN), fucosyl-α...

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Main Authors: Antonio Rubio-Del-Campo, Roberto Gozalbo-Rovira, Eva M. Moya-Gonzálvez, Juan Alberola, Jesús Rodríguez-Díaz, María J. Yebra
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Gut Microbes
Subjects:
Online Access:http://dx.doi.org/10.1080/19490976.2021.1914377
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spelling doaj-d3c627e5f3c34236a90f217141dc341b2021-07-06T12:16:09ZengTaylor & Francis GroupGut Microbes1949-09761949-09842021-01-0113110.1080/19490976.2021.19143771914377Infant gut microbiota modulation by human milk disaccharides in humanized microbiome miceAntonio Rubio-Del-Campo0Roberto Gozalbo-Rovira1Eva M. Moya-Gonzálvez2Juan Alberola3Jesús Rodríguez-Díaz4María J. Yebra5IATA-CSICUniversidad de ValenciaIATA-CSICUniversidad de ValenciaUniversidad de ValenciaIATA-CSICHuman milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-α1,3-GlcNAc (3FN), fucosyl-α1,6-GlcNAc, lacto-N-biose (LNB) and galacto-N-biose on the fecal microbiota and host–microbiota interactions. 16S rRNA amplicon sequencing showed that certain bacterial genera significantly increased (Ruminococcus and Oscillospira) or decreased (Eubacterium and Clostridium) in all disaccharide-supplemented groups. Interestingly, cluster analysis differentiates the consumption of fucosyl-oligosaccharides from galactosyl-oligosaccharides, highlighting the disappearance of Akkermansia genus in both fucosyl-oligosaccharides. An increment of the relative abundance of Coprococcus genus was only observed with 3FN. As well, LNB significantly increased the relative abundance of Bifidobacterium, whereas the absolute levels of this genus, as measured by quantitative real-time PCR, did not significantly increase. OTUs corresponding to the species Bifidobacterium longum, Bifidobacterium adolescentis and Ruminococcus gnavus were not present in the control after the 3-week intervention, but were shared among the donor and specific disaccharide groups, indicating that their survival is dependent on disaccharide supplementation. The 3FN-feeding group showed increased levels of butyrate and acetate in the colon, and decreased levels of serum HDL-cholesterol. 3FN also down-regulated the pro-inflammatory cytokine TNF-α and up-regulated the anti-inflammatory cytokines IL-10 and IL-13, and the Toll-like receptor 2 in the large intestine tissue. The present study revealed that the four disaccharides show efficacy in producing beneficial compositional shifts of the gut microbiota and in addition, the 3FN demonstrated physiological and immunomodulatory roles.http://dx.doi.org/10.1080/19490976.2021.1914377fucosyl-α-13-n-acetylglucosaminefucosyl-α-16-n-acetylglucosaminelacto-n-biosegalacto-n–biosehuman milk oligosaccharidesinfant fecal microbiotahumanized mouse modelshort-chain fatty acidscytokines
collection DOAJ
language English
format Article
sources DOAJ
author Antonio Rubio-Del-Campo
Roberto Gozalbo-Rovira
Eva M. Moya-Gonzálvez
Juan Alberola
Jesús Rodríguez-Díaz
María J. Yebra
spellingShingle Antonio Rubio-Del-Campo
Roberto Gozalbo-Rovira
Eva M. Moya-Gonzálvez
Juan Alberola
Jesús Rodríguez-Díaz
María J. Yebra
Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice
Gut Microbes
fucosyl-α-1
3-n-acetylglucosamine
fucosyl-α-1
6-n-acetylglucosamine
lacto-n-biose
galacto-n–biose
human milk oligosaccharides
infant fecal microbiota
humanized mouse model
short-chain fatty acids
cytokines
author_facet Antonio Rubio-Del-Campo
Roberto Gozalbo-Rovira
Eva M. Moya-Gonzálvez
Juan Alberola
Jesús Rodríguez-Díaz
María J. Yebra
author_sort Antonio Rubio-Del-Campo
title Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice
title_short Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice
title_full Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice
title_fullStr Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice
title_full_unstemmed Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice
title_sort infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice
publisher Taylor & Francis Group
series Gut Microbes
issn 1949-0976
1949-0984
publishDate 2021-01-01
description Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-α1,3-GlcNAc (3FN), fucosyl-α1,6-GlcNAc, lacto-N-biose (LNB) and galacto-N-biose on the fecal microbiota and host–microbiota interactions. 16S rRNA amplicon sequencing showed that certain bacterial genera significantly increased (Ruminococcus and Oscillospira) or decreased (Eubacterium and Clostridium) in all disaccharide-supplemented groups. Interestingly, cluster analysis differentiates the consumption of fucosyl-oligosaccharides from galactosyl-oligosaccharides, highlighting the disappearance of Akkermansia genus in both fucosyl-oligosaccharides. An increment of the relative abundance of Coprococcus genus was only observed with 3FN. As well, LNB significantly increased the relative abundance of Bifidobacterium, whereas the absolute levels of this genus, as measured by quantitative real-time PCR, did not significantly increase. OTUs corresponding to the species Bifidobacterium longum, Bifidobacterium adolescentis and Ruminococcus gnavus were not present in the control after the 3-week intervention, but were shared among the donor and specific disaccharide groups, indicating that their survival is dependent on disaccharide supplementation. The 3FN-feeding group showed increased levels of butyrate and acetate in the colon, and decreased levels of serum HDL-cholesterol. 3FN also down-regulated the pro-inflammatory cytokine TNF-α and up-regulated the anti-inflammatory cytokines IL-10 and IL-13, and the Toll-like receptor 2 in the large intestine tissue. The present study revealed that the four disaccharides show efficacy in producing beneficial compositional shifts of the gut microbiota and in addition, the 3FN demonstrated physiological and immunomodulatory roles.
topic fucosyl-α-1
3-n-acetylglucosamine
fucosyl-α-1
6-n-acetylglucosamine
lacto-n-biose
galacto-n–biose
human milk oligosaccharides
infant fecal microbiota
humanized mouse model
short-chain fatty acids
cytokines
url http://dx.doi.org/10.1080/19490976.2021.1914377
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