Liapis Christos Ch
Democritus University of Thrace, Alexandroupolis, Greece.
Therapy Center for Dependent Individuals, Athens, Greece.
Psychiatriki. 2024 Dec 15. doi: 10.22365/jpsych.2024.024.
The gut microbiome, which comprises symbiotic bacteria colonizing the human digestive tract, undergoes dynamic changes during the lifespan, as evidenced by the fact that the number of species and the diversity of their composition decrease significantly with age. The aim of this review is to illuminate bilateral neuroimmunological pathways that determine the role of gut microbiome dysbiosis, not only as a cause but also as a byproduct of many neurodegenerative diseases of the CNS, such as Alzheimer's disease (AD) and Parkinson's disease (PD), but also in the frame of several behavioral and psychiatric pathological conditions such as depressive and anxiety disorders, schizophrenia, and autism spectrum disorder (ASD). Dysbiosis, in particular, reveals a model of "deceptive" mimicry of host molecules that might cause abnormal folding ("misfolding") and pathological aggregation of Aβ-peptide, leading to its dispersion through the gut-brain axis, precipitating microglia cell activation. By controlling myelination at the prefrontal cortex (PFC), a crucial area for multifaceted cognitive behavior, forecasting, and decision-making, the gut/microbiome-brain axis influences mood and social behavior, since major depressive disorder is correlated to white matter disturbance in the PFC, due to disregulations in the expression of myelin-related mRNA in this area. The gut microbiome is altered in psychosis compared to healthy controls, while medication with antipsychotics may result in reduced microbial community diversity. The vagus nerve, as a key element of the parasympathetic nervous system, regulating immune responses, may "detect" gut microbiome metabolites and transfer this intestinal information to the CNS, through its afferents, as in a "pseudo-neurotransmission" process. Scientific interest towards microbiome-based therapies increases as psychobiotics (which are strains of probiotics/prebiotics with specific properties to influence the gut-brain axis) appear to be able to exercise a beneficial effect in many CNS disorders. Lifestyle modifications, such as dietary interventions via psychobiotics intake that might enhance the gut microbiome's ability to produce beneficial metabolites that exert therapeutic effects on intestinal permeability, cognitive function, and immunity, may reveal new research pathways and therapeutic directions leading to a radical change of the "epistemology paradigm" as far as prevention and treatment of major neuro-psychiatric disorders is concerned.
肠道微生物群由定殖于人类消化道的共生细菌组成，在整个生命周期中会发生动态变化，物种数量及其组成的多样性会随着年龄的增长而显著减少，这一事实就证明了这一点。本综述的目的是阐明双向神经免疫途径，这些途径决定了肠道微生物群失调的作用，肠道微生物群失调不仅是中枢神经系统许多神经退行性疾病（如阿尔茨海默病（AD）和帕金森病（PD））的病因，也是其副产品，同时还涉及一些行为和精神病理状况，如抑郁和焦虑症、精神分裂症以及自闭症谱系障碍（ASD）。特别是，失调揭示了一种对宿主分子的“欺骗性”模仿模式，这可能会导致Aβ肽异常折叠（“错误折叠”）和病理性聚集，导致其通过肠脑轴扩散，促使小胶质细胞激活。通过控制前额叶皮质（PFC）的髓鞘形成（PFC是多方面认知行为、预测和决策的关键区域），肠道/微生物群-脑轴会影响情绪和社交行为，因为重度抑郁症与PFC中的白质紊乱有关，这是由于该区域髓鞘相关mRNA表达失调所致。与健康对照相比，精神病患者的肠道微生物群会发生改变，而使用抗精神病药物可能会导致微生物群落多样性降低。迷走神经作为副交感神经系统的关键要素，调节免疫反应，可能会“检测”肠道微生物群代谢产物，并通过其传入神经将这种肠道信息传递给中枢神经系统，就像在“假神经传递”过程中一样。随着精神益生菌（即具有影响肠脑轴特定特性的益生菌/益生元菌株）似乎能够在许多中枢神经系统疾病中发挥有益作用，对基于微生物群的疗法的科学兴趣与日俱增。生活方式的改变，如通过摄入精神益生菌进行饮食干预，这可能会增强肠道微生物群产生有益代谢产物的能力，这些代谢产物对肠道通透性、认知功能和免疫力具有治疗作用，这可能会揭示新的研究途径和治疗方向，从而在重大神经精神疾病的预防和治疗方面引发“认识论范式”的根本转变。
