Pierce Ellen S
13212 East Blossey Avenue, Spokane Valley, Washington, USA.
Open Vet J. 2019 Apr;9(1):5-12. doi: 10.4314/ovj.v9i1.2. Epub 2019 Jan 22.
An increased rate of diffuse gliomas, including glioblastoma, has been noted in livestock farmers in Western countries. Some researchers have suggested that a zoonotic virus or bacteria present in the livestock animal's feces or manure may be a possible etiologic factor. subspecies (MAP), the cause of a chronic enteropathy in domestic livestock and a probable zoonosis, is heavily excreted in an infected animal's feces or manure, contaminating soil and ground on the animal's farm. Once excreted in an animal's feces, MAP lasts indefinitely in a dormant but viable form, and easily spreads outside farms to the surrounding environment. MAP's presence throughout the soil in countries where MAP infection of domestic livestock is extensive and long-standing may explain the increased rates of glioblastoma in tennis and baseball players who handle balls coated with MAP-contaminated dirt. MAP infection is consistent with glioblastoma's two defining histopathologic characteristics: endothelial cell proliferation and pseudopalisading necrosis. MAP is a non-tuberculous or atypical mycobacterium, which can cause hypoxic necrotizing granulomas, granulomas that resemble areas of pseudopalisading necrosis. There are known bacterial causes of endothelial cell proliferation. Almost unique amongst intracellular bacteria, MAP's variant isocitrate dehydrogenase 1 (IDH1) enzyme, a type 2-oxoglutarate ferredoxin oxidoreductase, can use a host cell's cytosolic α-ketoglutarate in its own Krebs or tricarboxylic acid cycle. MAP's ability to use a host cell's α-ketoglutarate may explain the survival advantage of the cytosolic IDH1 enzyme mutation for patients with diffuse gliomas including glioblastoma, astrocytoma, and oligdendroglioma, a mutation that results in a reduced supply of cytosolic α-ketoglutarate. MAP may therefore be one possible infectious cause of glioblastoma and the other histologic categories of diffuse glioma.
西方国家的畜牧养殖者中，包括胶质母细胞瘤在内的弥漫性胶质瘤发病率有所上升。一些研究人员认为，家畜粪便或粪肥中存在的人畜共患病毒或细菌可能是一个潜在的病因。副结核分枝杆菌（MAP）是家畜慢性肠道疾病的病因，也可能是人畜共患病，大量存在于受感染动物的粪便或粪肥中，污染动物养殖场的土壤和地面。一旦随动物粪便排出，MAP会以休眠但仍具活力的形式无限期存活，并很容易传播到养殖场外的周边环境。在国内家畜MAP感染广泛且长期存在的国家，土壤中普遍存在MAP，这或许可以解释为何接触被MAP污染泥土包裹的球的网球和棒球运动员中，胶质母细胞瘤发病率上升。MAP感染与胶质母细胞瘤的两个典型组织病理学特征相符：内皮细胞增殖和假栅栏状坏死。MAP是一种非结核或非典型分枝杆菌，可导致缺氧性坏死性肉芽肿，这种肉芽肿类似于假栅栏状坏死区域。已知存在导致内皮细胞增殖的细菌病因。在细胞内细菌中几乎独一无二的是，MAP的变异异柠檬酸脱氢酶1（IDH1），一种2-氧代戊二酸铁氧还蛋白氧化还原酶，可在自身的三羧酸循环中利用宿主细胞的胞质α-酮戊二酸。MAP利用宿主细胞α-酮戊二酸的能力，可能解释了弥漫性胶质瘤（包括胶质母细胞瘤、星形细胞瘤和少突胶质细胞瘤）患者中，胞质IDH1酶突变带来的生存优势，这种突变会导致胞质α-酮戊二酸供应减少。因此，MAP可能是胶质母细胞瘤及其他组织学类型的弥漫性胶质瘤的一种潜在感染病因。
