Ketogenic diet modulates gut microbiota composition in an experimental model of cerebral palsy

Cerebral palsy (CPa) is a neurodevelopmental disorder often accompanied by gastrointestinal dysfunction and dysbiosis of the gut microbiota (GM). The ketogenic diet (KD) has demonstrated neuroprotective and anti-inflammatory properties in neurological diseases, yet its effects on GM in CPa remain poorly understood.

This study aimed to evaluate the impact of KD on the GM composition in an experimental model of CPa.

Male Wistar rats were assigned to four groups (n = 10) according to healthy status and KD intervention: healthy control (C), healthy ketogenic diet (K), cerebral palsy (P), and cerebral palsy with ketogenic diet (PK). CPa was induced by perinatal anoxia and sensorimotor restriction, and, from postnatal day 25-65, animals received a standard or a KD. Body weight, food, and energy intake were monitored. Fecal samples were collected at day 65 for 16S rRNA sequencing and bioinformatics analyses.

The CPa condition was associated with reduced body weight, decreased food intake, and marked alterations in GM composition, characterized by increased abundance of Proteobacteria, Enterobacteriaceae, and Escherichia-Shigella, along with reduced levels of Bifidobacterium and Lactobacillus. KD intervention in animals with CPa was associated with coordinated shifts in GM structure, including reduced representation of taxa linked to inflammatory profiles and increased abundance of short-chain fatty acid-producing bacterial groups, such as members of the Lachnospiraceae and Ruminococcaceae families.

Overall, these findings suggest that modulation of GM may contribute to the neuroprotective and anti-inflammatory effects of the KD, highlighting GM as a potential therapeutic target for CPa-associated comorbidities.