Metabolomics and Proteomics Laboratory, Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland.
J Affect Disord. 2025 Jan 1;368:180-190. doi: 10.1016/j.jad.2024.09.058. Epub 2024 Sep 11.
Understanding the multifactorial nature of major depressive disorder (MDD) is crucial for tailoring treatments. However, the complex interplay of various factors underlying the development and progression of MDD poses significant challenges. Our previous study demonstrated improvements in cognitive functions in MDD patients undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) supplemented with Lactobacillus plantarum 299v (LP299v).
To elucidate the biochemical mechanisms underlying cognitive functions improvements, we explored underlying metabolic changes. We employed multi-platform metabolomics, including LC-QTOF-MS and CE-TOF-MS profiling, alongside chiral LC-QqQ-MS analysis for amino acids.
Supplementation of SSRI treatment with LP299v intensified the reduction of long-chain acylcarnitines, potentially indicating improved mitochondrial function. LP299v supplementation reduced N-acyl taurines more than four times compared to the placebo, suggesting a substantial impact on restoring biochemical balance. The LP299v-supplemented group showed increased levels of oxidized glycerophosphocholine (oxPC). Additionally, LP299v supplementation led to higher levels of sphingomyelins, L-histidine, D-valine, and p-cresol.
This exploratory study suggests potential metabolic pathways influenced by LP299v supplementation. However, the need for further research hinders the ability to draw definitive conclusions.
Observed metabolic changes were linked to mitochondrial dysfunction, inflammation, oxidative stress, and gut microbiota disruption. Despite the subtle nature of this alterations, our research successfully detected these differences and connected them to the metabolic disruptions associated with MDD. Our findings emphasise the intricate relationship between metabolism, gut microbiota, and mental health prompting further research into the mechanisms of action of probiotics in MDD treatment.
理解重度抑郁症（MDD）的多因素性质对于定制治疗至关重要。然而，MDD 发展和进展背后各种因素的复杂相互作用带来了重大挑战。我们之前的研究表明，接受选择性 5-羟色胺再摄取抑制剂（SSRIs）治疗并补充植物乳杆菌 299v（LP299v）的 MDD 患者的认知功能得到改善。
为了阐明认知功能改善的生化机制，我们探讨了潜在的代谢变化。我们采用多平台代谢组学，包括 LC-QTOF-MS 和 CE-TOF-MS 谱分析以及手性 LC-QqQ-MS 分析氨基酸。
SSRIs 治疗中补充 LP299v 可强化长链酰基辅酶 A 的减少，这可能表明线粒体功能得到改善。与安慰剂相比，LP299v 补充剂使 N-酰基牛磺酸减少了四倍以上，这表明其对恢复生化平衡有重大影响。LP299v 补充组的氧化甘油磷酸胆碱（oxPC）水平升高。此外，LP299v 补充组的鞘磷脂、L-组氨酸、D-缬氨酸和对甲酚水平升高。
这项探索性研究表明 LP299v 补充可能影响潜在的代谢途径。但是，进一步研究的需要限制了得出明确结论的能力。
观察到的代谢变化与线粒体功能障碍、炎症、氧化应激和肠道微生物群破坏有关。尽管这些改变很细微，但我们的研究成功地检测到了这些差异，并将其与与 MDD 相关的代谢紊乱联系起来。我们的研究结果强调了代谢、肠道微生物群和心理健康之间的复杂关系，促使进一步研究益生菌在 MDD 治疗中的作用机制。
