| Gestational diabetes mellitus(GDM)is a systemic metabolic disorder that occurs during pregnancy and its incidence is increasing year by year.Human milk is known to be the main source of nutrition for infants,containing all the necessary nutrients for infant growth and development.Moreover,human feeding can effectively protect mothers and infants from the adverse effects of GDM.However,the human feeding rate and duration for mothers with GDM are often shorter and changes in the composition of human milk can directly affect the gut microbiota of newborns,thereby influencing their long-term growth and development.Human milk oligosaccharides and N-glycans on glycoproteins act as prebiotics and promote the growth of beneficial gut bacteria in infants,thereby contributing to overall infant health.This study systematically elucidated the differences in the structure and content of oligosaccharides and N-glycans in human milk from mothers with GDM and healthy mothers,as well as the differences in gut microbiota composition in their offspring,and explored the effects of GDM human milk oligosaccharides and N-glycans on infant gut microbiota.The results of this study provide theoretical support and guidance for pregnancy interventions,to help reduce the adverse effects of GDM on maternal and infant health.The following are the main contents of this study:(1)Effect of GDM on the type and content of oligosaccharides in human milk and changes with lactation.Specifically,this study examined the differences in HMO types and levels between GDM and healthy mother colostrum and mature milk.Results showed significant differences in HMO structures and levels between GDM and healthy mother milk.In terms of structural composition,healthy mother milk(including colostrum and mature milk)had a richer diversity of non-fucosylated,monofucosylated,and fucosylated HMOs compared to GDM mother milk.In terms of oligosaccharide content,five specific oligosaccharides,Namely,2’-FL,LNT,LNn T,α3’-GL,and 6’-SL were 1.8,2.3,1.6,1.9,and 3.8 times higher than the HMO in colostrum of mothers with GDM.In addition,DSL,α3’-GL,LNn T,and 3-FL were 7.7,2.2,1.5,and 1.6 times more abundant in mature milk of healthy mothers than oligosaccharides in mature milk of mothers with GDM.These differences suggest that GDM affects glycosyltransferase and lacto-glycosidase activities and thus changes the type and content of oligosaccharides in human milk during different lactation periods.(2)Effect of GDM on the type and content of N-glycans in human milk and changes with lactation.In this chapter,colostrum and mature milk samples from mothers with GDM were compared to samples from healthy mothers to analyze the differences in N-glycan types and contents.The study also explored the macro-and micro-heterogeneity of glycoproteins.Results showed that the Nglycans in GDM mothers milk differed from those in healthy mother milk in terms of structure and content.In terms of structure,healthy mother colostrum contained more unmodified N-glycans and both fucosylated and sialylated N-glycan types than GDM mother colostrum.In addition,healthy mothers mature milk contained more fucosylated N-glycan types.With regard to the macroheterogeneity of lactose glycoproteins,the number of glycoproteins with two or more glycosylation sites was similar in healthy mother colostrum and GDM mother colostrum.In terms of microheterogeneity of lactose glycoproteins,the number of different N-glycans attached to the same glycosylation site of the same protein was higher in healthy mother milk(colostrum and mature milk)than in GDM mother milk(colostrum and mature milk).These glycoproteins were mainly composed of lactoferrin and members of the secretory immunoglobulin A family(PIGR,IGHA,JCHAIN).In terms of content,the total content of fucosylated N-glycans was higher in GDM mother milk(colostrum and mature milk),while the content of the other four types of N-glycans was higher in healthy mother milk.Compared to GDM mother colostrum,the content of five different N-glycans attached to two glycosylation sites of lactoferrin was significantly upregulated in healthy mother colostrum,while the content of nine different N-glycans attached to two glycosylation sites of PIGR was significantly downregulated.Compared to GDM mother mature milk,the content of two Nglycans attached to two glycosylation sites of lactoferrin was significantly upregulated and one Nglycan was significantly downregulated in healthy mother mature milk.These differences suggest that GDM affects the type as well as the amount of N-glycans on glycoproteins in human milk during different lactation periods.(3)Effects of human milk oligosaccharides and N-glycans from mothers with GDM at different stages of lactation on infant gut microbiota.This study investigated the differences in gut microbiota composition in infants fed by mothers with GDM(colostrum and mature milk)compared to healthy mothers(colostrum and mature milk),as well as the regulatory effects of oligosaccharides and Nglycans from GDM mother milk(colostrum and mature milk)on infant gut microbiota.The results showed that there were differences in gut microbiota composition between infants of healthy mothers and GDM mothers.Compared to infants of GDM mothers,the abundance of beneficial bacteria in the gut of infants of healthy mothers was higher,while the abundance of pathogenic or proinflammatory bacteria was lower.Additionally,it was found that the abundance of Bifidobacterium increased with lactation duration,with Bifidobacterium breve being dominant in the gut of infants of healthy mothers,while Bifidobacterium longum was dominant in the gut of infants of GDM mothers.The relative abundance of different Lactobacilli and Bacteroides was also different in the gut of infants of healthy mothers compared to GDM mothers.In GDM mother colostrum,most oligosaccharides were positively correlated with Bifidobacterium breve.2’-FL was positively correlated with Bifidobacterium longum and lactobacilli Plantarum.In GDM mother mature milk,most oligosaccharides were positively correlated with Bifidobacterium longum.α3’-GL was significantly positively correlated with Bifidobacterium breve.Additionally,all five types of Nglycans in GDM mother colostrum and mature milk were positively correlated with lactobacilli Plantarum.Fucosylated,sialylated,and both fucosylated and sialylated N-glycans were positively correlated with Bifidobacterium longum.These differences suggest that GDM causes disorders in the infant gut microbiota,while oligosaccharides and N-glycans in GDM human milk can promote the proliferation of beneficial bacteria in the infant gut microbiota. |
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