Caso Javier R, Balanzá-Martínez Vicent, Palomo Tomás, García-Bueno Borja
Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid; Avda. Complutense s/n. 28040 Madrid, Spain.
Curr Pharm Des. 2016;22(40):6122-6133. doi: 10.2174/1381612822666160906160911.
The underlying pathophysiology of schizophrenia still remains elusive. Thus, there is a pressing need to identify novel targets for the development of new interventions and elucidate related biomarkers for the identification and monitoring of potentially responsive patients. In this sense, several hypotheses involving immune/inflammatory changes and the consequent oxidative/nitrosative stress, as well as a dysregulation in the immuno-inflammatory response have come into sight.
Considering the great amount of genes encoded by the microbiome and the evidences pointing to the potential role of the gut microbiota on several neurologic and psychiatric diseases, the aim of this review is to evaluate the possible role of these organisms in the immunopathogenesis of schizophrenia. To that end, we will focus not only on gut microbiota dysbiosis but also on bacterial translocation as an inductor of neuroinflammation.
Studies have shown that the gut microbiota may play a key role in the immunopathogenesis of schizophrenia and that essential pathways implicated in the etiopathophysiology of schizophrenia are also regulated by the microbiota-gut-brain (MGB) axis. Moreover, studies also indicate a possible role of the innate immunity through the Toll-like receptors (TLRs) and their activation by bacterial translocation, as a consequence of intestinal dysfunction, in the pathophysiology of psychotic disorders.
This is a promising area of investigation with huge potential to offer advances in the realm of personalized medicine and accordingly, future research should examine several microbiota-targeted therapies in order to improve symptoms and to decrease the immune dysregulation seen in patients with schizophrenia.
精神分裂症的潜在病理生理学仍不清楚。因此,迫切需要确定新干预措施开发的新靶点,并阐明相关生物标志物,以识别和监测可能有反应的患者。从这个意义上说,一些涉及免疫/炎症变化以及随之而来的氧化/亚硝化应激,以及免疫炎症反应失调的假说已经出现。
考虑到微生物组编码的大量基因以及肠道微生物群在几种神经和精神疾病中的潜在作用的证据,本综述的目的是评估这些微生物在精神分裂症免疫发病机制中的可能作用。为此,我们不仅将关注肠道微生物群失调,还将关注细菌易位作为神经炎症的诱导因素。
研究表明,肠道微生物群可能在精神分裂症的免疫发病机制中起关键作用,并且精神分裂症病因病理生理学中涉及的重要途径也受微生物-肠道-脑(MGB)轴调节。此外,研究还表明,由于肠道功能障碍,通过Toll样受体(TLR)及其被细菌易位激活的先天免疫在精神障碍的病理生理学中可能发挥作用。
这是一个有前景的研究领域,在个性化医学领域有巨大的进步潜力,因此,未来的研究应研究几种针对微生物群的疗法,以改善症状并减少精神分裂症患者中出现的免疫失调。