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L-arginine metabolism ameliorates age-related cognitive impairment by Amuc_1100-mediated gut homeostasis maintaining
Aging Cell ( IF 8.0 ) Pub Date : 2024-01-18 , DOI: 10.1111/acel.14081 Jiamin He 1, 2, 3 , Tongyao Hou 1, 2, 3 , Qiwen Wang 1, 2, 3 , Qingyi Wang 1, 2, 3 , Yao Jiang 2, 3, 4 , Luyi Chen 3, 5 , Jilei Xu 1, 2, 3 , Yadong Qi 1, 2, 3 , Dingjiacheng Jia 2, 3, 4 , Yanrou Gu 3, 6 , Lidan Gao 3, 7 , Yingcong Yu 3, 6 , Lan Wang 1, 2, 3 , Lijun Kang 8 , Jianmin Si 1, 2, 3 , Liangjing Wang 2, 3, 4 , Shujie Chen 1, 2, 3
Aging Cell ( IF 8.0 ) Pub Date : 2024-01-18 , DOI: 10.1111/acel.14081 Jiamin He 1, 2, 3 , Tongyao Hou 1, 2, 3 , Qiwen Wang 1, 2, 3 , Qingyi Wang 1, 2, 3 , Yao Jiang 2, 3, 4 , Luyi Chen 3, 5 , Jilei Xu 1, 2, 3 , Yadong Qi 1, 2, 3 , Dingjiacheng Jia 2, 3, 4 , Yanrou Gu 3, 6 , Lidan Gao 3, 7 , Yingcong Yu 3, 6 , Lan Wang 1, 2, 3 , Lijun Kang 8 , Jianmin Si 1, 2, 3 , Liangjing Wang 2, 3, 4 , Shujie Chen 1, 2, 3
Affiliation
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Aging-induced cognitive impairment is associated with a loss of metabolic homeostasis and plasticity. An emerging idea is that targeting key metabolites is sufficient to impact the function of other organisms. Therefore, more metabolism-targeted therapeutic intervention is needed to improve cognitive impairment. We first conducted untargeted metabolomic analyses and 16S rRNA to identify the aging-associated metabolic adaption and intestinal microbiome change. Untargeted metabolomic analyses of plasma revealed L-arginine metabolic homeostasis was altered during the aging process. Impaired L-arginine metabolic homeostasis was associated with low abundance of intestinal Akkermansia muciniphila (AKK) colonization in mice. Long-term supplementation of AKK outer membranes protein-Amuc_1100, rescued the L-arginine level and restored cognitive impairment in aging mice. Mechanically, Amuc_1100 acted directly as a source of L-arginine and enriched the L-arginine-producing bacteria. In aged brain, Amuc_1100 promoted the superoxide dismutase to alleviated oxidation stress, and increased nitric oxide, derivatives of L-arginine, to improve synaptic plasticity. Meanwhile, L-arginine repaired lipopolysaccharide-induced intestinal barrier damage and promoted growth of colon organoid. Our findings indicated that aging-related cognitive impairment was closely associated with the disorders of L-arginine metabolism. AKK-derived Amuc_1100, as a potential postbiotic, targeting the L-arginine metabolism, might provide a promising therapeutic strategy to maintain the intestinal homeostasis and cognitive function in aging.
中文翻译：
L-精氨酸代谢通过 Amuc_1100 介导的肠道稳态维持改善与年龄相关的认知障碍
衰老引起的认知障碍与代谢稳态和可塑性的丧失有关。一个新兴的想法是，针对关键代谢物足以影响其他生物体的功能。因此，需要更多针对代谢的治疗干预来改善认知障碍。我们首先进行了非靶向代谢组学分析和 16S rRNA，以确定与衰老相关的代谢适应和肠道微生物组变化。血浆非靶向代谢组学分析表明，L-精氨酸代谢稳态在衰老过程中发生了改变。 L-精氨酸代谢稳态受损与小鼠肠道阿克曼氏菌( AKK ) 定植丰度低相关。长期补充AKK外膜蛋白Amuc_1100，可以挽救衰老小鼠的L-精氨酸水平并恢复认知障碍。从机械角度来看，Amuc_1100 直接作为 L-精氨酸来源并富集 L-精氨酸生产细菌。在衰老的大脑中，Amuc_1100 促进超氧化物歧化酶以减轻氧化应激，并增加一氧化氮（L-精氨酸的衍生物）以改善突触可塑性。同时，L-精氨酸修复脂多糖引起的肠道屏障损伤并促进结肠类器官的生长。我们的研究结果表明，衰老相关的认知障碍与L-精氨酸代谢紊乱密切相关。 AKK衍生的 Amuc_1100 作为一种潜在的后生元，针对 L-精氨酸代谢，可能提供一种有前景的治疗策略，以维持衰老过程中的肠道稳态和认知功能。
更新日期：2024-01-18
中文翻译：
L-精氨酸代谢通过 Amuc_1100 介导的肠道稳态维持改善与年龄相关的认知障碍
衰老引起的认知障碍与代谢稳态和可塑性的丧失有关。一个新兴的想法是，针对关键代谢物足以影响其他生物体的功能。因此，需要更多针对代谢的治疗干预来改善认知障碍。我们首先进行了非靶向代谢组学分析和 16S rRNA，以确定与衰老相关的代谢适应和肠道微生物组变化。血浆非靶向代谢组学分析表明，L-精氨酸代谢稳态在衰老过程中发生了改变。 L-精氨酸代谢稳态受损与小鼠肠道阿克曼氏菌( AKK ) 定植丰度低相关。长期补充AKK外膜蛋白Amuc_1100，可以挽救衰老小鼠的L-精氨酸水平并恢复认知障碍。从机械角度来看，Amuc_1100 直接作为 L-精氨酸来源并富集 L-精氨酸生产细菌。在衰老的大脑中，Amuc_1100 促进超氧化物歧化酶以减轻氧化应激，并增加一氧化氮（L-精氨酸的衍生物）以改善突触可塑性。同时，L-精氨酸修复脂多糖引起的肠道屏障损伤并促进结肠类器官的生长。我们的研究结果表明，衰老相关的认知障碍与L-精氨酸代谢紊乱密切相关。 AKK衍生的 Amuc_1100 作为一种潜在的后生元，针对 L-精氨酸代谢，可能提供一种有前景的治疗策略，以维持衰老过程中的肠道稳态和认知功能。
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