(P22-026-24) Maternal Intake of Mediterranean Diet Protects Newborn Mice From Western Diet-Induced Gut Dysbiosis and Metabolic Deficits

Objectives: To investigate whether Mediterranean diet (MD) intervention in early-life can alleviate Western diet (WD)-induced metabolic deficits and microbiome dysbiosis in infants.

Methods: C57BL/6 breeders were maintained either on WD or MD. Offspring, exposed to diets during gestation and weaning, were later randomized into two groups: WD or MD for 10-weeks, forming four diet groups based on mother-infant dyads: WDWD, MDWD, WDMD, and MDMD. Bodyweight and diet intake were measured weekly. Gut microbiome was assessed at weaning and 8-weeks by 16S rRNA sequencing. Spatial and learning memory were assessed by T-maze test. Serum lipid and inflammatory markers were assessed at endpoint. Neurodevelopmental and gut epithelial function markers were assessed by mRNA expression assays.

Results: MDWD group displayed lower alpha-diversity compared to WDWD group after 8-weeks. Beta-diversity varied at weaning and remained distinct between MDWD and WDWD groups. MD intervention for 8-weeks eradicated the compositional differences observed at weaning. The Firmicutes/Bacteroidota ratio increased in MDWD group compared to WDWD group. MDWD group had higher fasting glucose and circulating lipoproteins but lower AST levels than WDWD group. Colonic and ileal expression of pore-forming proteins claudin-2 and -15 was significantly lower in MDMD and MDWD groups compared to WDWD group. ZO1 expression in colon was significantly higher in MD-WD group. Ileal expression of IL1β, TNF⍺, and IL8 was lower in MD-MD group. MD-exposed pups had increased levels of butyrate-producing gut bacterial taxa Intestinimonas and Roseburia, whereas WD-exposed pups had elevated presence of Coriobacteriaceae, Streptococcus, and Enterococcus.

Conclusions: Maternal intake of Mediterranean-style dietary pattern during pregnancy and lactation fosters a healthier neonatal microbiome enriched with beneficial bacteria and protects from metabolic deficits caused by a Western-style dietary pattern.

Funding Sources: Juntendo University and Florida State University