Department of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Nutrients. 2022 Jun 27;14(13):2661. doi: 10.3390/nu14132661.
The involvement of the gut microbiota and the metabolites of colon-residing bacteria in brain disease pathogenesis has been covered in a growing number of studies, but comparative literature is scarce. To fill this gap, we explored the contribution of the microbiota-gut-brain axis to the pathophysiology of seven brain-related diseases (attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, major depressive disorder, and bipolar disorder). In this article, we discussed changes in bacterial abundance and the metabolic implications of these changes on disease development and progression. Our central findings indicate that, mechanistically, all seven diseases are associated with a leaky gut, neuroinflammation, and over-activated microglial cells, to which gut-residing bacteria and their metabolites are important contributors. Patients show a pro-inflammatory shift in their colon microbiota, harbouring more Gram-negative bacteria containing immune-triggering lipopolysaccharides (LPS) in their cell walls. In addition, bacteria with pro-inflammatory properties (, , ) are found in higher abundances, whereas lower abundances of anti-inflammatory bacteria (, , , , , , , , ) are reported, when compared to healthy controls. On the metabolite level, aberrant levels of short-chain fatty acids (SCFAs) are involved in disease pathogenesis and are mostly found in lower quantities. Moreover, bacterial metabolites such as neurotransmitters (acetylcholine, dopamine, noradrenaline, GABA, glutamate, serotonin) or amino acids (phenylalanine, tryptophan) also play an important role. In the future, defined aberrations in the abundance of bacteria strains and altered bacterial metabolite levels could likely be possible markers for disease diagnostics and follow-ups. Moreover, they could help to identify novel treatment options, underlining the necessity for a deeper understanding of the microbiota-gut-brain axis.
越来越多的研究表明，肠道微生物群及其在结肠中定植的细菌代谢物与脑疾病的发病机制有关，但相关文献比较匮乏。为了填补这一空白，我们探讨了微生物群-肠-脑轴对七种与脑相关疾病（注意缺陷多动障碍、自闭症谱系障碍、精神分裂症、阿尔茨海默病、帕金森病、重度抑郁症和双相情感障碍）的病理生理学的贡献。在本文中，我们讨论了细菌丰度的变化以及这些变化对疾病发展和进展的代谢影响。我们的主要发现表明，从机制上讲，所有七种疾病都与肠漏、神经炎症和过度激活的小胶质细胞有关，而肠道中定植的细菌及其代谢物是这些疾病的重要诱因。患者的结肠微生物群发生促炎转变，其细胞壁中含有更多引发免疫的革兰氏阴性菌脂多糖（LPS）。此外，还发现具有促炎特性的细菌（、、）丰度增加，而抗炎细菌（、、、、、、、、）丰度降低，与健康对照组相比。在代谢物水平上，异常的短链脂肪酸（SCFAs）水平参与了疾病的发病机制，且其含量通常较低。此外，细菌代谢物，如神经递质（乙酰胆碱、多巴胺、去甲肾上腺素、GABA、谷氨酸、血清素）或氨基酸（苯丙氨酸、色氨酸）也起着重要作用。未来，细菌菌株丰度的明确异常和细菌代谢物水平的改变可能成为疾病诊断和随访的可能标志物。此外，它们还可以帮助确定新的治疗选择，这突显了深入了解微生物群-肠-脑轴的必要性。
