Milk Exosomes From Gestational Diabetes Mellitus Parturients Demonstrate Weaker Ability to Promote Intestinal...

Area of Science:

• Perinatology
• Gastroenterology
• Molecular Biology

Background:

• Human milk exosomes (HMEs) play a crucial role in infant development.
• Gestational diabetes mellitus (GDM) may alter the composition and function of HMEs.
• Understanding GDM-HME effects on infant gut health is vital for early intervention.

Purpose of the Study:

• To investigate differences between GDM-HMEs (GDM-EXO) and healthy HMEs (HEA-EXO) in promoting offspring intestinal development.
• To analyze differential microRNAs (miRNAs) and their correlation with gut microbiota (GM) in infants exposed to GDM-EXO vs. HEA-EXO.
• To assess the impact of GDM-EXO and HEA-EXO on intestinal morphology and gut barrier function in a mouse model.

Main Methods:

• Quantitative PCR (qPCR) to verify differential miRNAs in GDM-EXO and HEA-EXO.
• 16S rDNA amplicon sequencing to analyze infant gut microbiota composition.
• Gavage of C57BL/6J mice with GDM-EXO or HEA-EXO, followed by histological staining, Western blotting for gut barrier proteins (ZO-1, Occludin), and GM analysis.

Main Results:

• GDM-EXO exhibited altered miRNA profiles (upregulated: hsa-miR-19b-3p, hsa-miR-148a-3p, hsa-miR-320a-3p; downregulated: hsa-miR-429) compared to HEA-EXO.
• Infants exposed to GDM-EXO showed altered gut microbiota (increased Coriobacteriaceae, Clostridiaceae, Erysipelotrichaceae, Erysipelatoclostridiaceae; decreased Lactobacillaceae).
• GDM-EXO demonstrated a weaker capacity to enhance intestinal morphology (villus length, villus length-to-crypt depth ratio, goblet cell number) and gut barrier integrity (ZO-1, Occludin) in mice compared to HEA-EXO.

Conclusions:

• Human milk exosomes from GDM parturients (GDM-EXO) have a diminished ability to promote intestinal development in offspring compared to those from healthy parturients (HEA-EXO).
• Differential miRNAs and gut microbiota alterations are associated with GDM-EXO's impact on infant gut health.
• These findings highlight the potential negative effects of GDM on infant gut development mediated by exosomal components in breast milk.