High levels of fucosylation and sialylation of milk N‐glycans from mothers with gestational diabetes mellitus alter the offspring gut microbiome and immune balance in mice

Abstract

Gestational diabetes mellitus (GDM) is significantly associated with allergen sensitization in early childhood, and this may influence the gut microbiome and immune system of the children. In addition to mother‐to‐child transmission of microbes, milk glycans play a pivotal role in shaping the gut microbiome of infants. A previous study has demonstrated alterations in the major milk N‐glycans of mothers with GDM. However, the impact of these changes on the gut microbiome and immune response of the neonates has yet to be studied. Here, we aimed to compare the glycosylation levels of various milk glycans between normal and GDM mice, and to characterize the intestinal microbiome and immune responses of the offspring after weaning. We found that GDM mouse milk contained significantly higher concentrations of fucosylated and sialylated N‐glycans than control mice, but there was no difference in the concentration of milk oligosaccharides between the groups. The differences in milk N‐glycans had direct effects on the intestinal microbiome of the offspring, which in turn affected their immune response upon challenge with ovalbumin (OVA), with disruptions in the Th1/Th2 and Th17/Treg cell balances. This study lays the foundation for further research and development of specific nutritional care for the offspring of GDM mothers.

Core Fucosylation of Intestinal Epithelial Cells Protects Against Salmonella Typhi Infection via Up-Regulating the Biological Antagonism of Intestinal Microbiota

“…Given that the commensal bacteria of the gastrointestinal tract play an important role in protecting the host from pathogenic bacteria infection to maintain intestinal homeostasis (Mueller and Macpherson, 2006;Backhed et al, 2012). The imbalance of microbiota caused by pathogen infection is considered to be closely related to inflammation, obesity, fucosylation, sialylation and other metabolic factors (Boulange et al, 2016;Zhou et al, 2020). It has been reported that Salmonella infection enhanced the levels of proinflammatory cytokines IL-1β, IL-8, and LITNF.…”

The Anti-Inflammatory Effect and Mucosal Barrier Protection of Clostridium butyricum RH2 in Ceftriaxone-Induced Intestinal Dysbacteriosis

“…In order to investigate the effects of CB RH2 on proliferation of T cells in the PPs of mice, total lymphocytes from the PPs of the control mice were isolated and incubated with different concentrations of CB RH2 supernatant and cell lysate, respectively. According to the culture method as described in our previous study (Zhou et al, 2020), 1 mL of the CB RH2 culture broth (OD 600 = 1.5) was centrifuged at 2,500 rpm for 5 min, and the culture supernatant was regarded as bacterial secretion. Then the pellet was resuspended in MRS for ultrasonic crushing to release the intracellular components, followed by centrifuging for 5 min at 2,500 rpm.…”

The Intestinal Dysbiosis of Mothers with Gestational Diabetes Mellitus (GDM) and Its Impact on the Gut Microbiota of Their Newborns

“…It was found that the Bacteroides and Clostridiales_vadinBB60 were more abundant, while Prevotella was much lower in GDM mice than in control mice. However, most of these bacteria were found to have a common trend in GDM offspring; it was found that Bacteroides were more abundant, while Lactobacillus and Prevotella were less abundant in the gut of offspring fed by GDM mothers [ 48 ]. GDM can change the microbiota of pregnant women and newborns, revealing another mode of heredity.…”

“…According to the connection mode, the glycans on glycoproteins are divided into N-polysaccharides and O-polysaccharides. It was found that more than 70% of human milk proteins are glycosylated, and human lactose proteins play a defensive role against infectious diseases by producing antibacterial and immunomodulatory activities of passive immunity to breastfed infants [ 48 ]. Breast milk glycobiome has been shown to selectively enrich the infant gut microbiome with beneficial bacteria [ 51 ].…”

“…Due to the different abilities of intestinal microbiomes to use different types of glycans as carbon sources for growth and metabolism [ 48 ], differences in breast milk glycans may also affect the composition of intestinal microbial communities in offspring. In this context, some research groups have studied the glycobiome patterns in the breast milk of mothers with GDM, it was found that [ 53 ], compared to healthy women, the content of free oligosaccharides in the breast milk of GDM women was not different, but the total protein concentration and glycosylation level of sIgA in GDM breast milk were reduced; in contrast, the glycosylation of lactoferrin in the milk of GDM mothers was increased compared with the breast milk of healthy control mothers.…”