Milk Exosomes From Gestational Diabetes Mellitus Parturients Demonstrate Weaker Ability to Promote Intestinal Development in Offspring

Abstract

This study aims to investigate whether human milk exosomes from gestational diabetes mellitus (GDM-EXO) and healthy (HEA-EXO) parturients differ in regulating intestinal development in offspring. The differential miRNAs associated with intestinal development in GDM-EXO and HEA-EXO were verified by using qPCR and their relationships with gut microbiota (GM) in infants were analyzed. C57BL/6J mice were gavaged with 50 mg/kg·BW HEA-EXO or GDM-EXO. The intestinal morphology, gut barriers, ZO-1 and Occludin, and GM were determined by histological staining, Western blotting, and 16S rDNA amplicon sequencing, respectively. Hsa-miR-19b-3p, hsa-miR-148a-3p, and hsa-miR-320a-3p were upregulated, and hsa-miR-429 was decreased in GDM-EXO compared to HEA-EXO. The GDM parturients’ infants had increased intestinal Coriobacteriaceae, Clostridiaceae, Erysipelotrichaceae, Erysipelatoclostridiaceae, and fewer Lactobacillaceae than the healthy parturient's infants. The four differential miRNAs in GDM-EXO all correlated with the infants’ GM. GDM-EXO- and HEA-EXO-fed mice had greater villus lengths, villus length-to-crypt depth ratios, goblet cell numbers, elevated ZO-1 and Occludin, and lower crypt depths than control mice. HEA-EXO-fed mice had better intestinal morphology and gut barrier integrity than GDM-EXO-fed mice. GDM-EXO-fed mice had significantly decreased Lachnospiraceae and Oscillospiraceae than HEA-EXO-fed mice. GDM-EXO demonstrate weaker ability to promote intestinal development in offspring than HEA-EXO.