Wang Wenjing, Smith Melvyn, Ellis Richard, Savio Antonella, Nevel Amanda, Umamahesan Chianna, Pavlidis Polychronis, Hayee Bu' Hussain, Taylor David, Young Allan H, Charlett André, Dobbs Sylvia M, Dobbs R John
Host Microbiome Interaction, Clinical Pharmacology and Therapeutics, Institute of Pharmaceutical Science, King's College London, London SE1 9NH, UK.
South London and Maudsley NHS Foundation Trust, London SE5 8AB, UK.
Int J Mol Sci. 2024 Dec 6;25(23):13123. doi: 10.3390/ijms252313123.
Epidemiological and eradication trial evidence indicates that , a major causative factor in peptic ulcer and gastric cancer, is a driver of the hypokinesia of Parkinson's disease (PD). Psychological (cognitive impairment, depression and anxiety) and gastrointestinal (peptic ulceration and constipation) PD features can precede the symptomatic onset of motor features by decades. We hypothesise that the non- (NHPH), which have farm, companion and wild animals as their main hosts, can have a role in PD aetiopathogenesis. In those occupationally at risk of NHPH infection, we address whether there is increased mortality with PD, or depression or suicide. Our systematic review gave evidence that occupational exposure to animals/their products is associated with excess mortality with PD. Indeed, whilst livestock farming increased the risk, crop farming decreased it. Moreover, excess mortality from non-Hodgkin lymphoma in livestock farmers is compatible with NHPH being causal. Our scoping review showed that farmers, veterinarians and abattoir workers have an increased risk of depression and suicide; whether their depression is associated with being down the pathway to PD and/or the presence of infection needs investigation. Regarding species specificity, the link between the presence of NHPH in gastric biopsy and PD was described using a polymerase chain reaction (PCR) assay, targeting the most-commonly named NHPH, . We describe its redesign and optimisation as a probe-based PCR, confirming the exclusion of but not specificity (additionally identifying 6 species of a 22-NHPH-species panel). The exploration of the zoonotic hypothesis requires a non-invasive pan- PCR screen, allowing the detection and molecular grouping of species.
流行病学和根除试验证据表明，消化性溃疡和胃癌的一个主要致病因素是帕金森病（PD）运动功能减退的驱动因素。心理（认知障碍、抑郁和焦虑）和胃肠道（消化性溃疡和便秘）PD特征可能在运动特征出现症状前数十年就已存在。我们假设，以农场动物、伴侣动物和野生动物为主要宿主的非幽门螺杆菌（NHPH）可能在PD的发病机制中起作用。在那些有职业性NHPH感染风险的人群中，我们探讨是否存在PD、抑郁或自杀导致的死亡率增加。我们的系统评价提供了证据，表明职业性接触动物/其产品与PD导致的额外死亡率有关。事实上，虽然从事畜牧业会增加风险，但从事种植业则会降低风险。此外，畜牧养殖者中非霍奇金淋巴瘤导致的额外死亡率与NHPH具有因果关系相符。我们的范围综述表明，农民、兽医和屠宰场工人患抑郁症和自杀的风险增加；他们的抑郁症是否与PD发病过程以及/或NHPH感染的存在有关，需要进行调查。关于物种特异性，使用针对最常提及的NHPH即幽门螺杆菌的聚合酶链反应（PCR）检测方法，描述了胃活检中NHPH的存在与PD之间的联系。我们将其重新设计并优化为基于探针的PCR，证实排除了幽门螺杆菌，但未排除特异性（另外在一个包含22种NHPH的物种组中鉴定出6个物种）。对人畜共患病假说的探索需要一种非侵入性的泛PCR筛查方法，以检测NHPH物种并进行分子分类。
