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<p>The ketogenic diet (KD), a high-fat, low-carbohydrate regimen, has been shown to exert neuroprotective effects in various neurological models. This study explored how KD—alone or combined with antibiotic-induced gut microbiota depletion—affects cognition and neuroinflammation in aging. Thirty-two male rats (22&#xa0;months old) were assigned to four groups (<i>n</i> = 8): control diet (CD), ketogenic diet (KD), antibiotics with control diet (AB), and antibiotics with KD (KDAB). Diets were maintained for 10&#xa0;weeks; during the final week, AB and KDAB groups received a broad-spectrum antibiotic cocktail (ampicillin 1&#xa0;g/L, vancomycin 0.5&#xa0;g/L, neomycin 1&#xa0;g/L, and metronidazole 1&#xa0;g/L) in drinking water. Cognitive abilities were evaluated using the Morris Water Maze and Novel Object Recognition Test. BDNF and inflammatory cytokines (TNF-α, IL-1β, IL-10) were measured in the hippocampus and prefrontal cortex. KD and KDAB groups exhibited increased β-hydroxybutyrate and reduced glucose levels, enhanced cognitive performance, elevated BDNF and IL-10, and decreased TNF-α and IL-1β compared to non-KD groups. Although antibiotic treatment alone caused only a transient impairment in spatial memory and was associated with reduced TNF-α levels, the ketogenic diet—irrespective of microbiota status—consistently improved cognitive performance and elevated neuroprotective markers. These findings suggest that KD appears to promote brain resilience during aging, even in the presence of microbiota disruption.</p>

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Ketogenic Diet Mitigates Age-Related Cognitive Decline and Neuroinflammation in Rats, While Antibiotics Exacerbate Brain Health Risks

  • 期刊论文

  • 发表日期：

    2025年9月10日

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  • Oya Sayin,
  • Rabia Ilgin,
  • Erhan Caner Akkaya,
  • Mehmet Ates,
  • Ferda Hosgorler

摘要

The ketogenic diet (KD), a high-fat, low-carbohydrate regimen, has been shown to exert neuroprotective effects in various neurological models. This study explored how KD—alone or combined with antibiotic-induced gut microbiota depletion—affects cognition and neuroinflammation in aging. Thirty-two male rats (22 months old) were assigned to four groups (n = 8): control diet (CD), ketogenic diet (KD), antibiotics with control diet (AB), and antibiotics with KD (KDAB). Diets were maintained for 10 weeks; during the final week, AB and KDAB groups received a broad-spectrum antibiotic cocktail (ampicillin 1 g/L, vancomycin 0.5 g/L, neomycin 1 g/L, and metronidazole 1 g/L) in drinking water. Cognitive abilities were evaluated using the Morris Water Maze and Novel Object Recognition Test. BDNF and inflammatory cytokines (TNF-α, IL-1β, IL-10) were measured in the hippocampus and prefrontal cortex. KD and KDAB groups exhibited increased β-hydroxybutyrate and reduced glucose levels, enhanced cognitive performance, elevated BDNF and IL-10, and decreased TNF-α and IL-1β compared to non-KD groups. Although antibiotic treatment alone caused only a transient impairment in spatial memory and was associated with reduced TNF-α levels, the ketogenic diet—irrespective of microbiota status—consistently improved cognitive performance and elevated neuroprotective markers. These findings suggest that KD appears to promote brain resilience during aging, even in the presence of microbiota disruption.