INTRODUCTION: The ketogenic diet (KD), a high‑fat, low‑carbohydrate dietary intervention modifies the gut microbiota, one of a key regulator of early brain development.

AIM(S): This study explored how prenatal and early postnatal KD exposure influences overall brain and body growth and alters offspring gut microbiota at postnatal days (P) 2, 30, and 60.

METHOD(S): Wistar rats were assigned to a normal diet (ND), KD during gestation and lactation, or prenatal KD followed by ND after birth (KD/ND). Entire intestines were collected at P2, and caecal samples at P30 and P60. Microbiota composition was assessed by 16S rDNA sequencing (Illumina). Body and brain mass were recorded at a perfusion day (P30, P60).

RESULTS: Microbiota composition differed across diets and ages, with the strongest shifts observed in KD‑exposed P2 pups. In P2 animals, KD reduced Proteobacteria and increased Actinobacteria. At P30, KD elevated Bacteroidota and Firmicutes and decreased Actinobacteria. Changes were normalized by postnatal switch to ND. At P60, KD increased Proteobacteria, Bacteroidota, Firmicutes, and Actinobacteria, while ND introduction partially reversed these effects. KD‑exposed animals displayed significantly reduced body and brain mass compared with ND and KD/ND groups, while brain‑to‑body ratios were higher in KD and KD/ND animals.

CONCLUSIONS: Early KD exposure induces alterations general brain development and in gut microbiome structure. Such changes can be partially normalized by a standard diet introduction after birth. These findings highlight the potential role of microbiome-mediated mechanisms in KD-induced effects on neurodevelopment. It provides a strong foundation for investigating the extent to which KD affects the developing brain.

FINANCIAL SUPPORT: N/A