School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, Lancs, M1 7DN, U.K.
The Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, Lancs, M1 7DN, U.K.
Biol Rev Camb Philos Soc. 2018 Aug;93(3):1518-1557. doi: 10.1111/brv.12407. Epub 2018 Mar 25.
Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre-eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially 'external' causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress-induced iron dysregulation, and (ii) its ability to awaken dormant, non-replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens. The extensive evidence discussed here implies, as was found with ulcers, that almost all chronic, infectious diseases do in fact harbour a microbial component. What differs is simply the microbes and the anatomical location from and at which they exert damage. This analysis offers novel avenues for diagnosis and treatment.
自疫苗和抗生素成功征服许多急性传染病以来,目前最常见的疾病是慢性进行性疾病,并且都伴有炎症。这些疾病包括神经退行性疾病(如阿尔茨海默病、帕金森病)、血管疾病(如动脉粥样硬化、子痫前期、2 型糖尿病)和自身免疫性疾病(如类风湿关节炎和多发性硬化症),它们表面上似乎没有什么共同之处。事实上,它们都有显著的特征,特别是慢性炎症及其伴随的炎症细胞因子。如果没有潜在的最初的“外部”原因,这种影响是不会发生的,因此有必要寻找这些原因。我们采用系统方法,认为这些原因包括(i)应激诱导的铁失调,以及(ii)其唤醒宿主已感染的休眠、非复制微生物的能力。其他外部原因可能是饮食。这些微生物能够释放少量但具有重要功能的高度致炎分子,如脂多糖和脂磷壁酸。其后果包括严重的凝血异常,尤其是最近发现的血液淀粉样蛋白形成的凝血,导致细胞死亡和进一步释放致炎因子。这里讨论的广泛证据表明,正如发现溃疡那样,几乎所有慢性传染病实际上都有微生物成分。不同的只是微生物以及它们造成损害的解剖位置和部位。这种分析为诊断和治疗提供了新的途径。