Sayin Oya, Ilgin Rabia, Akkaya Erhan Caner, Ates Mehmet, Hosgorler Ferda
College of Vocational School of Health Services, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
Department of Physiology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
J Mol Neurosci. 2025 Sep 10;75(3):114. doi: 10.1007/s12031-025-02401-z.
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.
生酮饮食（KD）是一种高脂肪、低碳水化合物的饮食方案，已被证明在各种神经学模型中具有神经保护作用。本研究探讨了单独使用生酮饮食或联合抗生素诱导的肠道微生物群耗竭如何影响衰老过程中的认知和神经炎症。将32只雄性大鼠（22个月大）分为四组（n = 8）：对照饮食（CD）组、生酮饮食（KD）组、抗生素加对照饮食（AB）组和抗生素加KD（KDAB）组。饮食维持10周；在最后一周，AB组和KDAB组在饮用水中接受广谱抗生素鸡尾酒（氨苄青霉素1 g/L、万古霉素0.5 g/L、新霉素1 g/L和甲硝唑1 g/L）。使用莫里斯水迷宫和新物体识别测试评估认知能力。检测海马体和前额叶皮质中的脑源性神经营养因子（BDNF）和炎性细胞因子（TNF-α、IL-1β、IL-10）。与非KD组相比，KD组和KDAB组的β-羟基丁酸水平升高，葡萄糖水平降低，认知能力增强，BDNF和IL-10升高，TNF-α和IL-1β降低。尽管单独使用抗生素治疗仅导致空间记忆的短暂损害，并与TNF-α水平降低有关，但无论微生物群状态如何，生酮饮食均能持续改善认知能力并提高神经保护标志物水平。这些发现表明，即使在存在微生物群破坏的情况下，KD似乎也能促进衰老过程中的大脑恢复力。
