(OR14-03-24) Prenatal Omega-3 Fatty Acid Exposure Modulates Infant Microbiome and Mitigates Western Diet-Induced Metabolic and Neurodevelopmental Impairments

Objectives: To examine the effect of prenatal PUFAs (polyunsaturated fatty acids) exposure on gut microbiome, metabolism, and neurodevelopment in offspring raised on a Western diet (WD).

Methods: C57BL/6 breeders were maintained on WD with different fat sources: 20% anhydrous milk fat (SFA control), 20% corn oil (⍵6), or blend of 19% olive oil and 1% fish oil (⍵3). Offsprings were exposed to these diets only during gestation and nursing, followed by 10-week WD feeding. 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: Offspring from ⍵3-fed dams had relatively lower bodyweight and higher lean mass compared to SFA counterparts. The ⍵6 group had significantly higher cholesterol and LDL levels compared to SFA, while cholesterol/HDL and LDL/HDL ratio were lower in ⍵3 group compared to ⍵6 group. Both PUFA-fed groups had significantly different microbiome diversity compared to SFA at weaning and at 8-weeks. Abundance of Bacteroidota was lower, while Firmicutes were higher in PUFA-fed groups. Group-specific discriminatory taxa included enriched Erysipelotrichaceae and Lachnospiraceae_UCG001 in ⍵3 group, and increased Acetatifactor, Blautia, and Eubacterium_nodatum in ⍵6 group. The ⍵3 group exhibited lowest gut permeability, accompanied by reduced expression of pore-forming proteins claudin 2 and 15. Spatial and learning memory scores were significantly higher in ⍵3 group. Expression of BDNF (brain-derived neurotrophic factor) neuronal signaling was higher in hypothalamus and hippocampus of PUFA-fed groups. In hippocampus, neuroinflammatory genes were downregulated and upregulated by ⍵3 and ⍵6 groups, respectively.

Conclusions: The findings underpin the transgenerational benefits of incorporating ⍵3 fatty acids in maternal diets, fostering a healthier neonatal gut-brain development.

Funding Sources: Juntendo University and Florida State University