Study On The Effect And Mechanism Of Lactobacillus Reuteri On Improving Gestational Diabetes In Mice

Changes in secretory immunoglobulin A(s Ig A)coated bacteria from early to late pregnancy were associated with the development of gestational diabetes mellitus(GDM).SIg A-coated beneficial gut bacteria depleted in the GDM are potential probiotics for prevention of GDM.We investigated blood biochemistry,chronic inflammation,mucosal barrier biomarker and fecal s Ig A-coated microbiota in healthy early pregnancy(T1H,n =50),late pregnancy(T3H,n = 30)and women with GDM(T3D,n = 27).The “leaky gut”markers,zonulin and lipopolysaccharide(LPS),significantly increased in T3 D compared to the T3 H group.Shannon index of s Ig A-coated microbiota was elevated in late pregnancy compared to early pregnancy and was highest in the T3 D group(P < 0.001).T3 D group enriched with s Ig A-coated Escherichia and Streptococcus and depleted of Lactobacillus and Bifidobacterium.Blood glucose(BG)positively correlated with zonulin(P < 0.001)and LPS(P < 0.05).Lactobacillus reuteri negatively correlated with BG(P < 0.05),zonulin(P < 0.05)and LPS(P < 0.01).L.reuteri QS01 isolated from the feces of T1 H significantly reduced LPS released by gut microbiota from GDM individuals in vitro.We induced gestational diabetes susceptible mouse models using low protein chow:healthy control(F1 generation female mice fed normal chow,CON);GDM control(F1generation female mice produced by low protein chow feeding of F0 generation,GDM);Metformin treated GDM mice group(MET);L.rhamnosus HN001 treated GDM mice group(HN001);L.reuteri QS01 treated GDM mice group(QS01).Mice were gavaged after gestation to continue throughout the gestation period until the end of the oral glucose tolerance experiment.The results showed that fasting glucose,plasma C-reactive protein,tumor necrosis factor α,interleukin 6,lipopolysaccharide,and zonulin were significantly higher in the GDM group compared with the CON group(P < 0.05).Compared with the GDM group,the fasting glucose,serum interleukin 6,lipopolysaccharide and connexin levels were significantly lower in the QS01 group(P < 0.05).Pancreatic β-cell mass was significantly higher in the QS01 group(P < 0.05).Intestinal mucosal damage alleviated and m RNA expression levels of ZO-1 and Occludin proteins were significantly higher in QS01group(P < 0.001).The abundance of mouse colonic Desulfovibrio was significantly reduced(P < 0.05),the levels of plasma tryptamine,L-tryptophan and indole-3-lactate were significantly increased(P < 0.05),and the levels of fecal 3-indoleacetonitrile and 5-hydroxy-L-tryptophan were significantly increased(P < 0.01).In summary,GDM may be associated with intestinal mucosal damage and inflammation-induced disorders of s Ig A-coated bacteria.SIg A-coated L.reuteri QS01 may prevent GDM in vitro and in animal models by mechanisms that may involve: reduction of serum inflammatory factor levels,improvement of intestinal mucosal barrier damage,regulation of intestinal flora disorders,and blood and intestinal tryptophan metabolism.