Self Wade K, Holtzman David M
J Clin Invest. 2025 Jul 1;135(13). doi: 10.1172/JCI194443.
Recent studies have highlighted a possible role for gut microbiota in modulating Alzheimer's disease pathology, particularly through the actions of gut-derived metabolites and their influence on the immune system. In this issue of the JCI, Chandra et al. reveal that circulating levels of the gut microbiota-derived metabolite propionate affected amyloid burden and glial activation in a mouse model of Aβ amyloidosis. The study also identifies a mechanism for the therapeutic benefit of propionate supplementation, showing that propionate lowered peripheral IL-17 and suppressed Th17 cell activity. These results support the idea of therapeutic targeting of the gut/brain/immune axis, particularly via modulation of Th17 responses, and suggest translational strategies involving microbiome-based or immunological interventions for dementia prevention and treatment.
最近的研究强调了肠道微生物群在调节阿尔茨海默病病理过程中可能发挥的作用，特别是通过肠道衍生代谢产物的作用及其对免疫系统的影响。在本期《临床研究杂志》中，钱德拉等人发现，肠道微生物群衍生的代谢产物丙酸酯的循环水平影响了Aβ淀粉样变性小鼠模型中的淀粉样蛋白负荷和神经胶质细胞激活。该研究还确定了补充丙酸酯具有治疗益处的机制，表明丙酸酯降低了外周IL-17水平并抑制了Th17细胞活性。这些结果支持针对肠道/大脑/免疫轴进行治疗的观点，特别是通过调节Th17反应，并提出了涉及基于微生物群或免疫干预的转化策略，用于预防和治疗痴呆症。
