scholarly journals Sialylated human milk oligosaccharides program cognitive development through a non-genomic transmission mode

2021 ◽  
Author(s):  
Jonas Hauser ◽  
Edoardo Pisa ◽  
Alejandro Arias Vásquez ◽  
Flavio Tomasi ◽  
Alice Traversa ◽  
...  
Keyword(s):  
Cognitive Development ◽  
Gut Microbiota ◽  
Human Milk ◽  
Molecular Mechanisms ◽  
Brain Regions ◽  
Nervous System Development ◽  
Bioactive Molecules ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Eye Opening

AbstractBreastmilk contains bioactive molecules essential for brain and cognitive development. While sialylated human milk oligosaccharides (HMOs) have been implicated in phenotypic programming, their selective role and underlying mechanisms remained elusive. Here, we investigated the long-term consequences of a selective lactational deprivation of a specific sialylated HMO in mice. We capitalized on a knock-out (KO) mouse model (B6.129-St6gal1tm2Jxm/J) lacking the gene responsible for the synthesis of sialyl(alpha2,6)lactose (6′SL), one of the two sources of sialic acid (Neu5Ac) to the lactating offspring. Neu5Ac is involved in the formation of brain structures sustaining cognition. To deprive lactating offspring of 6′SL, we cross-fostered newborn wild-type (WT) pups to KO dams, which provide 6′SL-deficient milk. To test whether lactational 6′SL deprivation affects cognitive capabilities in adulthood, we assessed attention, perseveration, and memory. To detail the associated endophenotypes, we investigated hippocampal electrophysiology, plasma metabolomics, and gut microbiota composition. To investigate the underlying molecular mechanisms, we assessed gene expression (at eye-opening and in adulthood) in two brain regions mediating executive functions and memory (hippocampus and prefrontal cortex, PFC). Compared to control mice, WT offspring deprived of 6′SL during lactation exhibited consistent alterations in all cognitive functions addressed, hippocampal electrophysiology, and in pathways regulating the serotonergic system (identified through gut microbiota and plasma metabolomics). These were associated with a site- (PFC) and time-specific (eye-opening) reduced expression of genes involved in central nervous system development. Our data suggest that 6′SL in maternal milk adjusts cognitive development through a short-term upregulation of genes modulating neuronal patterning in the PFC.

scholarly journals Human Milk Glycomics and Gut Microbial Genomics in Infant Feces Show a Correlation between Human Milk Oligosaccharides and Gut Microbiota: A Proof-of-Concept Study

2014 ◽  
Vol 14 (1) ◽  
pp. 491-502 ◽  
Author(s):  
Maria Lorna A. De Leoz ◽  
Karen M. Kalanetra ◽  
Nicholas A. Bokulich ◽  
John S. Strum ◽  
Mark A. Underwood ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Human Milk ◽  
Proof Of Concept ◽  
Microbial Genomics ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Concept Study ◽  
Infant Feces

scholarly journals Human milk oligosaccharides: Shaping the infant gut microbiota and supporting health

2020 ◽  
Vol 72 ◽  
pp. 104074 ◽  
Author(s):  
Clodagh Walsh ◽  
Jonathan A. Lane ◽  
Douwe van Sinderen ◽  
Rita M. Hickey
Keyword(s):  
Gut Microbiota ◽  
Human Milk ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides

scholarly journals Fucosylated Human Milk Oligosaccharides and N-Glycans in the Milk of Chinese Mothers Regulate the Gut Microbiome of Their Breast-Fed Infants during Different Lactation Stages

mSystems ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Yaqiang Bai ◽  
Jia Tao ◽  
Jiaorui Zhou ◽  
Qingjie Fan ◽  
Man Liu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Human Milk ◽  
Gut Microbiome ◽  
Longitudinal Research ◽  
Protein Glycosylation ◽  
Glycoside Hydrolases ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Chinese Mothers ◽  
Breast Fed

ABSTRACT The milk glycobiome has a significant impact on the gut microbiota of infants, which plays a pivotal role in health and development. Fucosylated human milk oligosaccharides (HMOs) and N-glycans on milk proteins are beneficial for the development of healthy gut microbiota, and the fucosylation levels of these glycans can be affected by the maternal fucosyltransferase 2 gene (FUT2). Here, we present results of longitudinal research on paired milk and stool samples from 56 Chinese mothers (CMs) and their breast-fed children. Changes of HMOs and fucosylated N-glycans in milk of CMs at different lactation stages were detected, which allowed characterization of the major differences in milk glycans and consequential effects on the gut microbiome of infants according to maternal FUT2 status. Significant differences in the abundance of total and fucosylated HMOs between secretor and nonsecretor CMs were noted, especially during early lactation. Despite a tendency toward decreasing milk protein concentrations, the fucosylation levels of milk N-glycans increased during late lactation. The changes in the levels of fucosylated HMOs and milk N-glycans were highly correlated with the growth of Bifidobacterium spp. and Lactobacillus spp. in the gut of infants during early and later lactation, respectively. Enriched expression of genes encoding glycoside hydrolases, glycosyl transferases, ATP-binding cassette (ABC) transporters, and permeases in infants fed by secretor CMs contributed to the promotion of these bacteria in infants. Our data highlight the important role of fucosylated milk glycans in shaping the gut microbiome of infants and provide a solid foundation for development of “personalized” nutrition for Chinese infants. IMPORTANCE Human milk glycans provide a broad range of carbon sources for gut microbes in infants. Levels of protein glycosylation in human milk vary during lactation and may also be affected by the stages of gestation and lactation and by the secretor status of the mother. This was the first study to evaluate systematically dynamic changes in human milk oligosaccharides and fucosylated N-glycans in the milk of Chinese mothers with different secretor statuses during 6 months of lactation. Given the unique single nucleotide polymorphism site (rs1047781, A385T) on the fucosyltransferase 2 gene among Chinese populations, our report provides a specific insight into the milk glycobiome of Chinese mothers, which may exert effects on the gut microbiota of infants that differ from findings from other study cohorts.

scholarly journals Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2808
Author(s):  
Tanja Šuligoj ◽  
Louise Kristine Vigsnæs ◽  
Pieter Van den Abbeele ◽  
Athanasia Apostolou ◽  
Katia Karalis ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Human Milk ◽  
Barrier Function ◽  
Distal Colon ◽  
Human Milk Oligosaccharides ◽  
Gut Barrier ◽  
Milk Oligosaccharides ◽  
Caco2 Cell ◽  
Gut Barrier Function ◽  
The Impact

Human milk oligosaccharides (HMOs) shape the gut microbiota in infants by selectively stimulating the growth of bifidobacteria. Here, we investigated the impact of HMOs on adult gut microbiota and gut barrier function using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), Caco2 cell lines, and human intestinal gut organoid-on-chips. We showed that fermentation of 2’-O-fucosyllactose (2’FL), lacto-N-neotetraose (LNnT), and combinations thereof (MIX) led to an increase of bifidobacteria, accompanied by an increase of short chain fatty acid (SCFA), in particular butyrate with 2’FL. A significant reduction in paracellular permeability of FITC-dextran probe was observed using Caco2 cell monolayers with fermented 2’FL and MIX, which was accompanied by an increase in claudin-8 gene expression as shown by qPCR, and a reduction in IL-6 as determined by multiplex ELISA. Using gut-on-chips generated from human organoids derived from proximal, transverse, and distal colon biopsies (Colon Intestine-Chips), we showed that claudin-5 was significantly upregulated across all three gut-on-chips following treatment with fermented 2’FL under microfluidic conditions. Taken together, these data show that, in addition to their bifidogenic activity, HMOs have the capacity to modulate immune function and the gut barrier, supporting the potential of HMOs to provide health benefits in adults.

Human Milk Oligosaccharides Are Able to Impact the Gut Microbiota and Metabolites in Irritable Bowel Syndrome Patients

2018 ◽  
Vol 113 (Supplement) ◽  
pp. S1548
Author(s):  
Fran Jackson ◽  
Anisha Wijeyesekera ◽  
Glenn Gibson ◽  
Karin Fersøe Ødum ◽  
Helle Warrer Poulsen ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gut Microbiota ◽  
Human Milk ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Irritable Bowel
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