High-methionine diets induce impaired learning and memory function, dementia-like neurodegeneration, and Alzheimer’s disease, while low-methionine diets improve learning and memory function. We speculated that variations in intestinal microbiota may mediate these diametrically opposed effects; thus, this study aimed to verify this hypothesis. The ICR mice were fed either a low-methionine diet (LM, 0.17% methionine), normal methionine diet (NM, 0.86% methionine), or high-methionine diet (HM, 2.58% methionine) for 11 weeks. We found that HM diets damaged nonspatial recognition memory, working memory, and hippocampus-dependent spatial memory and induced anxiety-like behaviors in mice. LM diets improved nonspatial recognition memory and hippocampus-dependent spatial memory and ameliorated anxiety-like behavior, but the differences did not reach a significant level. Moreover, HM diets significantly decreased the abundance of putative short-chain fatty acid (SCFA)-producing bacteria (Roseburia, Blautia, Faecalibaculum, and Bifidobacterium) and serotonin-producing bacteria (Turicibacter) and significantly increased the abundance of proinflammatory bacteria Escherichia–Shigella. Of note, LM diets reversed the results. Consequently, the SCFA and serotonin levels were significantly decreased with HM diets and significantly increased with LM diets. Furthermore, HM diets induced hippocampal oxidative stress and inflammation and selectively downregulated the hippocampus-dependent memory-related gene expression, whereas LM diets selectively upregulated the hippocampus-dependent memory-related gene expression. In conclusion, dietary methionine via dose-dependent inhibition of SCFA production capacity contributed to a potential risk of cognitive dysfunction in mice.

中文翻译：

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膳食蛋氨酸通过剂量依赖性抑制短链脂肪酸生产能力导致小鼠认知功能障碍的潜在风险

高蛋氨酸饮食会导致学习和记忆功能受损、痴呆样神经变性和阿尔茨海默病，而低蛋氨酸饮食会改善学习和记忆功能。我们推测肠道微生物群的变化可能会介导这些截然相反的影响；因此，本研究旨在验证这一假设。ICR 小鼠被喂食低甲硫氨酸饮食（LM，0.17% 甲硫氨酸）、正常甲硫氨酸饮食（NM，0.86% 甲硫氨酸）或高甲硫氨酸饮食（HM，2.58% 甲硫氨酸），持续 11 周。我们发现 HM 饮食破坏了小鼠的非空间识别记忆、工作记忆和海马体依赖性空间记忆，并诱发了类似焦虑的行为。LM 饮食改善了非空间识别记忆和海马体依赖性空间记忆，并改善了类似焦虑的行为，但差异并未达到显着水平。此外，HM 饮食显着降低了假定的短链脂肪酸 (SCFA) 产生细菌的丰度（Roseburia、Blautia、Faecalibaculum和Bifidobacterium ) 和产生血清素的细菌 ( Turicibacter ) 并显着增加促炎细菌的丰度大肠杆菌-志贺氏菌. 值得注意的是，LM 饮食逆转了结果。因此，短链脂肪酸和血清素水平在 HM 饮食中显着降低，在 LM 饮食中显着升高。此外，HM 饮食诱导海马氧化应激和炎症并选择性下调海马依赖记忆相关基因表达，而 LM 饮食选择性上调海马依赖记忆相关基因表达。总之，膳食蛋氨酸通过剂量依赖性抑制 SCFA 生产能力导致小鼠认知功能障碍的潜在风险。