Abildgaard Anders, Elfving Betina, Hokland Marianne, Wegener Gregers, Lund Sten
Translational Neuropsychiatry Unit, Aarhus University, Skovagervej 2, 8240 Risskov, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.
Translational Neuropsychiatry Unit, Aarhus University, Skovagervej 2, 8240 Risskov, Denmark.
Psychoneuroendocrinology. 2017 May;79:40-48. doi: 10.1016/j.psyneuen.2017.02.014. Epub 2017 Feb 16.
The gut microbiota has recently emerged as an important regulator of brain physiology and behaviour in animals, and ingestion of certain bacteria (probiotics) therefore appear to be a potential treatment for major depressive disorder (MDD). However, some conceptual and mechanistical aspects need further elucidation. We therefore aimed at investigating whether the habitual diet may interact with the effect of probiotics on depression-related behaviour and further examined some potentially involved mechanisms underlying the microbe-mediated behavioural effects. Forty male Sprague-Dawley rats were fed a control (CON) or high-fat diet (HFD) for ten weeks and treated with either a multi-species probiotic formulation or vehicle for the last five weeks. Independently of diet, probiotic treatment markedly reduced depressive-like behaviour in the forced swim test by 34% (95% CI: 22-44%). Furthermore, probiotic treatment skewed the cytokine production by stimulated blood mononuclear cells towards IFNγ, IL2 and IL4 at the expense of TNFα and IL6. In addition, probiotics lowered hippocampal transcript levels of factors involved in HPA axis regulation (Crh-r1, Crh-r2 and Mr), whereas HFD increased these levels. A non-targeted plasma metabolomics analysis revealed that probiotics raised the level of indole-3-propionic acid, a potential neuroprotective agent. Our findings clearly support probiotics as a potential treatment strategy in MDD. Importantly, the efficacy was not attenuated by intake of a "Western pattern" diet associated with MDD. Mechanistically, the HPA axis, immune system and microbial tryptophan metabolism could be important in this context. Importantly, our study lend inspiration to clinical trials on probiotics in depressed patients.
肠道微生物群最近已成为动物大脑生理和行为的重要调节因子，因此摄入某些细菌（益生菌）似乎是治疗重度抑郁症（MDD）的一种潜在方法。然而，一些概念和机制方面需要进一步阐明。因此，我们旨在研究习惯性饮食是否会与益生菌对抑郁相关行为的影响相互作用，并进一步研究微生物介导的行为效应背后一些可能涉及的机制。40只雄性Sprague-Dawley大鼠被喂食对照（CON）或高脂饮食（HFD）10周，并在最后5周用多物种益生菌制剂或赋形剂进行处理。与饮食无关，益生菌治疗在强迫游泳试验中使抑郁样行为显著降低了34%（95%CI：22-44%）。此外，益生菌治疗使刺激的血液单核细胞产生的细胞因子向IFNγ、IL2和IL4倾斜，而以TNFα和IL6为代价。此外，益生菌降低了参与HPA轴调节的因子（Crh-r1、Crh-r2和Mr）的海马转录水平，而HFD则增加了这些水平。非靶向血浆代谢组学分析表明，益生菌提高了吲哚-3-丙酸的水平，这是一种潜在的神经保护剂。我们的研究结果明确支持益生菌作为MDD的一种潜在治疗策略。重要的是，与MDD相关的“西方模式”饮食的摄入并没有削弱其疗效。从机制上讲，HPA轴、免疫系统和微生物色氨酸代谢在这方面可能很重要。重要的是，我们的研究为抑郁症患者使用益生菌的临床试验提供了灵感。
