KETOGENIC DIET–INDUCED CHANGES IN EARLY-LIFE GUT MICROBIOTA DEVELOPMENT

Ketogenic diet (KD), a high‑fat, low‑carbohydrate intervention, strongly influences the gut microbiota, which plays a key role in early brain development. Study examined how prenatal and early postnatal KD exposure shapes offspring gut microbiota at postnatal days 2, 30, and 60, addressing a major gap in understanding KD’s impact on early neurodevelopment. Wistar rat offspring were exposed to a normal diet (ND), KD during prenatal and lactation periods, or KD prenatally followed by ND introduction after birth (KD/ND). In P2 animals, the entire intestine was collected, whereas in P30 and P60 animals, samples were obtained from the central caecum. Bacterial 16S rDNA was sequenced using Illumina to assess microbiota composition. Diet- and age-dependent differences in relative abundances of bacterial phyla were observed, with the most pronounced effects in KD-exposed P2 animals. In P2 offspring, KD exposure decreased Proteobacteria and increased Actinobacteria. In P30 animals, KD increased Bacteroidota and Firmicutes while reducing Actinobacteria. Changes were normalized by postnatal ND introduction. In P60 animals, KD increased Proteobacteria, Bacteroidota, Firmicutes, and Actinobacteria, whereas postnatal ND partially reversed these effects. Early KD exposure induces alterations in gut microbiome structure, reflecting potential dysbiosis, response to reduced fibre intake and metabolic adaptations to higher fat consumption. 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.