抗抑郁治疗前后重度抑郁症的血液微生物群和代谢组学特征：一项前瞻性病例对照研究。
Blood microbiota and metabolomic signature of major depression before and after antidepressant treatment: a prospective case-control study.
机构信息
From the INSERM UMRS 996 - Intestinal Microbiota, Macrophages and Liver Inflammation, DHU Hepatinov, Clamart, France (Ciocan, Cassard, Voican, Perlemuter); the University Paris-Saclay, University Paris-Sud, Faculty of Medicine, Le Kremlin-Bicêtre, France (Ciocan, Cassard, Becquemont, Verstuyft, Voican, El Asmar, Colle, Trabado, Chanson, Perlemuter, Corruble); the APHP, Hepato-Gastroenterology and Nutrition, Antoine-Béclère Hospital, Clamart, France (Ciocan, Voican, Perlemuter); the Centre for Clinical Research (CRC), Kremlin-Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre, France (Becquemont); the INSERM UMR-1178, CESP, "MOODS" Team, Le Kremlin-Bicêtre, France (Becquemont, Verstuyft, El Asmar, David, Corruble); the Department of Molecular Genetics, Pharmacogenetics and Hormones, Kremlin-Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre, 94275, France (Becquemont, Verstuyft, Trabado); the Psychiatry Department, Kremlin-Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre, 94275, France (Colle, Corruble); the University Paris-Saclay, University Paris-Sud, Faculty of Pharmacy, Chatenay-Malabry, 92 296, France (David); the INSERM 1185, University Paris-Saclay, University Paris-Sud, Faculty of Medicine, Le Kremlin-Bicêtre, 94276, France (Trabado, Chanson); the Department of Endocrinology, Saint-Antoine Hospital, AP-HP, Sorbonne University, University Paris 6, Paris, France (Feve); the INSERM UMR S_938, Saint-Antoine Research Centre, Paris, France (Feve); and the Department of Endocrinology and Reproductive Diseases, Kremlin-Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre, 94275, France (Chanson).
出版信息
J Psychiatry Neurosci. 2021 May 19;46(3):E358-E368. doi: 10.1503/jpn.200159.
BACKGROUND
The microbiota interacts with the brain through the gut-brain axis, and a distinct dysbiosis may lead to major depressive episodes. Bacteria can pass through the gut barrier and be found in the blood. Using a multiomic approach, we investigated whether a distinct blood microbiome and metabolome was associated with major depressive episodes, and how it was modulated by treatment.
METHODS
In this case-control multiomic study, we analyzed the blood microbiome composition, inferred bacterial functions and metabolomic profile of 56 patients experiencing a current major depressive episode and 56 matched healthy controls, before and after treatment, using 16S rDNA sequencing and liquid chromatography coupled to tandem mass spectrometry.
RESULTS
The baseline blood microbiome in patients with a major depressive episode was distinct from that of healthy controls (patients with a major depressive episode had a higher proportion of Janthinobacterium and lower levels of Neisseria) and changed after antidepressant treatment. Predicted microbiome functions confirmed by metabolomic profiling showed that patients who were experiencing a major depressive episode had alterations in the cyanoamino acid pathway at baseline. High baseline levels of Firmicutes and low proportions of Bosea and Tetrasphaera were associated with response to antidepressant treatment. Based on inferred baseline metagenomic profiles, bacterial pathways that were significantly associated with treatment response were related to xenobiotics, amino acids, and lipid and carbohydrate metabolism, including tryptophan and drug metabolism. Metabolomic analyses showed that plasma tryptophan levels are independently associated with response to antidepressant treatment.
LIMITATIONS
Our study has some limitations, including a lack of information on blood microbiome origin and the lack of a validation cohort to confirm our results.
CONCLUSION
Patients with depression have a distinct blood microbiome and metabolomic signature that changes after treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients who are experiencing a major depressive episode.
背景
微生物群通过肠脑轴与大脑相互作用，而明显的失调可能导致重度抑郁症发作。细菌可以穿过肠道屏障并存在于血液中。我们采用多组学方法，研究了独特的血液微生物群和代谢组是否与重度抑郁症发作有关，以及治疗如何调节它。
方法
在这项病例对照多组学研究中，我们分析了 56 名正在经历当前重度抑郁症发作的患者和 56 名匹配的健康对照者的血液微生物组组成、推断的细菌功能和代谢组学特征，使用 16S rDNA 测序和液相色谱-串联质谱法。在治疗前后。
结果
重度抑郁症患者的基线血液微生物组与健康对照组不同（重度抑郁症患者的 Janthinobacterium 比例较高，Neisseria 水平较低），并在抗抑郁治疗后发生变化。通过代谢组学分析证实的预测微生物组功能表明，正在经历重度抑郁症发作的患者在基线时存在氰基氨基酸途径的改变。高基线Firmicutes 水平和低比例的 Bosea 和 Tetrasphaera 与抗抑郁治疗反应相关。基于推断的基线宏基因组谱，与治疗反应显著相关的细菌途径与外源性物质、氨基酸以及脂质和碳水化合物代谢有关，包括色氨酸和药物代谢。代谢组学分析表明，血浆色氨酸水平与抗抑郁治疗反应独立相关。
局限性
我们的研究存在一些局限性，包括缺乏血液微生物组起源的信息以及缺乏验证队列来确认我们的结果。
结论
患有抑郁症的患者具有独特的血液微生物组和代谢组学特征，这些特征在治疗后会发生变化。失调可能是治疗重度抑郁症患者的新治疗靶点和预后工具。
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