Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder.

IF 5.8 1区 医学 Q1 PSYCHIATRY
Min Jia, Yajuan Fan, Qingyan Ma, Ding Yang, Yunpeng Wang, Xiaoyan He, Binbin Zhao, Xianyan Zhan, Zhiyang Qi, Yifan Ren, Ziqing Dong, Feng Zhu, Wei Wang, Yuan Gao, Xiancang Ma
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Abstract

Evidence suggests that complex interactions among the gut microbiome, metabolic abnormalities, and brain have important etiological and therapeutic implications in major depressive disorder (MDD). However, the influence of microbiome-gut-brain cross-talk on cognitive impairment in MDD remains poorly characterized. We performed serum metabolomic profiling on 104 patients with MDD and 77 healthy controls (HCs), and also performed fecal metagenomic sequencing on a subset of these individuals, including 79 MDD patients and 60 HCs. The findings were validated in a separate cohort that included 40 patients with MDD and 40 HCs using serum-targeted metabolomics. Abnormal bile acid metabolism was observed in patients with MDD, which is related to cognitive dysfunction. The following gut microbiota corresponded to changes in bile acid metabolism and enzyme activities involved in the bile acid metabolic pathway, including Lachnospiraceae (Blautia_massiliensis, Anaerostipes_hadrus, Dorea_formicigenerans, and Fusicatenibacter_saccharivorans), Ruminococcaceae (Ruminococcus_bromii, Flavonifractor_plautii, and Ruthenibacterium_lactatiformans), and Escherichia_coli. Furthermore, a combinatorial marker classifier that robustly differentiated patients with MDD from HCs was identified. In conclusion, this study provides insights into the gut-brain interactions in the cognitive phenotype of MDD, indicating a potential therapeutic strategy for MDD-associated cognitive impairment by targeting the gut microbiota and bile acid metabolism.

重度抑郁症患者肠道菌群失调通过胆汁酸代谢促进认知障碍。
有证据表明,肠道微生物群、代谢异常和大脑之间的复杂相互作用在重度抑郁症(MDD)中具有重要的病因学和治疗意义。然而,微生物群-肠-脑串扰对重度抑郁症患者认知功能障碍的影响尚不清楚。我们对104名MDD患者和77名健康对照(hc)进行了血清代谢组学分析,并对这些个体的一部分进行了粪便宏基因组测序,其中包括79名MDD患者和60名hc。研究结果在一个单独的队列中得到验证,该队列包括40名重度抑郁症患者和40名hcc患者,使用血清靶向代谢组学。MDD患者胆汁酸代谢异常,与认知功能障碍有关。以下肠道微生物群与胆囊酸代谢和胆囊酸代谢途径中酶活性的变化相对应,包括毛螺旋科(Blautia_massiliensis, Anaerostipes_hadrus, Dorea_formicigenerans, Fusicatenibacter_saccharivorans),瘤胃球菌科(Ruminococcus_bromii, flavractor_plautii, Ruthenibacterium_lactatiformans)和大肠杆菌。此外,还发现了一种组合标记分类器,可以将MDD患者与hcc患者区分开来。总之,本研究提供了对MDD认知表型中肠-脑相互作用的见解,表明了针对肠道微生物群和胆汁酸代谢的MDD相关认知障碍的潜在治疗策略。
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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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