肠道微生物群通过重塑肠-脑能量代谢来缓解抑郁症，这一成果由南方医科大学曹雄团队经过不懈努力而取得。2026年3月31日出版的《细胞—代谢》发表了这项成果。

课题组研究人员以代谢分析为主题，揭示抑郁症和无主题抑郁症患者粪便肌酸升高以及血浆和脑脊液肌酸降低。外源性肌酸产生由肠道菌群介导的抗抑郁样作用。假结肠双歧杆菌被确定为抑郁症中显著减少的肠道细菌种类，与肌酸吸收受损相关。随后补充双歧杆菌增强了肌酸的抗抑郁作用。在机制上，假长叶假杆菌衍生的醋酸盐通过组蛋白乙酰化促进肠上皮细胞中肌酸转运蛋白（Slc6a8）的表达。Slc6a8介导肌酸的抗抑郁作用。神经元肌酸缺乏影响能量代谢和神经生理功能。在服用抗抑郁药的抑郁症患者中，联合使用肌酸和双歧杆菌可提高血浆肌酸水平，降低抑郁评分。这些发现确定了双歧杆菌-肌酸组合是一种很有前途的抗抑郁策略，并强调了肠-脑能量代谢在抑郁症中的关键作用。

据了解，尽管外周脑串扰调节能量代谢，但其在抑郁症中的作用尚不清楚。

附：英文原文

Title: The gut microbiota alleviates depression by remodeling gut-brain energy metabolism

Author: Cheng-Lin Lu, Jing Ren, Yueshiyuan Lei, Xiao-Ying Lian, Hao-Tian Jiang, Fang Guo, Liang-Yu Chen, Jia-Wen Mo, Hongyun Mao, Jun Fan, Guangyan Wu, Wan-Qian Ye, You-Lu Wen, Haitao Sun, Yan He, Jiubo Zhao, Xiong Cao

Issue&Volume: 2026-03-31

Abstract: Although peripheral-brain crosstalk regulates energy metabolism, its role in depression remains unclear. Here, we used metabolic profiling to reveal elevated fecal creatine alongside reduced plasma and cerebrospinal fluid creatine in both patients with depression and mouse depression models. Exogenous creatine produced antidepressant-like effects mediated by gut microbiota. Bifidobacterium pseudolongum was identified as a significantly reduced gut bacterial species in depression, correlating with impaired creatine absorption. Subsequent supplementation with Bifidobacterium enhanced the antidepressant effects of creatine. Mechanistically, B. pseudolongum-derived acetate promoted the creatine transporter (Slc6a8) expression in intestinal epithelial cells via histone acetylation. The Slc6a8 mediated the antidepressant-like effects of creatine. Neuronal creatine deficiency influenced energetic metabolism and neurophysiological function. In patients with depression taking antidepressants, co-administration of creatine and Bifidobacterium increased plasma creatine levels and reduced depression scores. These findings identify the Bifidobacterium-creatine combination as a promising antidepressant strategy and highlight the critical role of gut-brain energy metabolism in depression.

DOI: 10.1016/j.cmet.2026.03.002

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(26)00096-3