The body's microbiome represents an actively regulated network of novel mechanisms that potentially underlie the etiology and pathophysiology of a wide range of diseases. For complex brain disorders such as schizophrenia, understanding the cellular and molecular pathways that intersect the bidirectional gut-brain axis is anticipated to lead to new methods of treatment. The means by which the microbiome might differ across neuropsychiatric and neurological disorders are not known. Brain disorders as diverse as schizophrenia, major depression, Parkinson's disease and multiple sclerosis appear to share a common pathology of an imbalanced community of commensal microbiota, often measured in terms of a leaky gut phenotype accompanied by low level systemic inflammation. While environmental factors associated with these disease states might contribute to intestinal pathologies, products from a perturbed microbiome may also directly promote specific signs, symptoms and etiologies of individual disorders. We hypothesize that in schizophrenia, it is the putatively unique susceptibility related to genes that modulate the immune system and the gut-brain pleiotropy of these genes which leads to a particularly neuropathological response when challenged by a microbiome in dysbiosis. Consequences from exposure to this dysbiosis may occur during pre- or post-natal time periods and thus may interfere with normal neurodevelopment in those who are genetically predisposed. Here, we review the evidence from the literature which supports the idea that the intersection of the microbiome and immune gene susceptibility in schizophrenia is relevant etiologically and for disease progression. Figuring prominently at both ends of the gut-brain axis and at points in between are proteins encoded by genes found in the major histocompatibility complex (MHC), including select MHC as well as non-MHC complement pathway genes.

中文翻译：

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精神分裂症中微生物群和神经活性免疫基因相互作用的破译。

人体的微生物组代表着一种积极调控的新型机制网络，这些机制可能是各种疾病的病因学和病理生理学的基础。对于精神分裂症等复杂的脑部疾病，了解与双向肠脑轴相交的细胞和分子途径有望带来新的治疗方法。微生物组在神经精神病学和神经系统疾病中可能不同的方法尚不清楚。精神分裂症，重度抑郁症，帕金森氏病和多发性硬化症等各种脑疾病似乎具有共同的共生微生物群落失调的常见病理，通常以肠道渗漏表型伴低水平的全身性炎症来衡量。尽管与这些疾病状态相关的环境因素可能会导致肠道病理，但来自微生物组干扰的产品也可能直接促进个体疾病的特定体征，症状和病因。我们假设在精神分裂症中，与调节免疫系统的基因和这些基因的肠脑多效性有关的基因可能具有独特的易感性，当受到微生物菌群挑战时，会导致特别的神经病理反应。暴露于这种营养不良的后果可能发生在出生前或出生后的时期，因此可能会干扰那些具有遗传易感性的人的正常神经发育。这里，我们回顾了文献中的证据，这些证据支持精神分裂症中微生物组和免疫基因易感性的交集在病因学和疾病进展方面均具有相关性。主要在肠道组织相容性复合体（MHC）中发现的基因编码的蛋白质在肠脑轴的两端和中间点突出，包括选择的MHC以及非MHC补体途径基因。