Fox James G, Handt Lawrence, Xu Shilu, Shen Zeli, Dewhirst Floyd E, Paster Bruce J, Dangler Charles A, Lodge Ken, Motzel Sherri, Klein Hilton
Massachusetts Institute of Technology, Cambridge, MA, *Merck Research Laboratories, West Point, PA and †Forsyth Institute, Boston, MA, USA.
J Med Microbiol. 2001 May;50(5):421-429. doi: 10.1099/0022-1317-50-5-421.
Chronic, idiopathic diffuse colitis is a well recognised clinical and pathological entity in captive rhesus monkeys. Six rhesus monkeys were diagnosed with clinically debilitating, chronic diarrhoea. Histologically, colonic tissues were characterised as chronic, moderate to severe colitis and typhlitis, with diffuse mononuclear inflammation of lamina propria, reactive lymphoid hyperplasia and multifocal micro-abscesses. Colonic tissues were cultured for Salmonella spp. and Shigella spp.; all results were negative. Samples were negative for Clostridium difficile A and B toxins, and special stains of colonic tissue for acid-fast bacteria were also negative. The six diarrhoeic monkeys tested gave negative results for serum IgG antibodies to herpes B virus, STLV, SRV and SIV. Colonic tissue from the six diarrhoeic and two clinically normal monkeys with histologically confirmed colitis from the same colony were also subjected to micro-aerobic culture. Micro-aerobic cultures from all eight monkeys incubated at 37 degrees C and 42 degrees C revealed pinpoint or spreading colonies on antibiotic-containing media. Bacteria were identified as gram-negative, oxidase positive and urease negative. Of the nine strains characterised biochemically, two separate biotypes (corresponding to different species by 16S rRNA analysis) were identified. One biotype (type 1), from non-diarrhoeic monkeys and the second biotype (type 2) from diarrhoeic animals with subclinical chronic colonic inflammation, differed by catalase activity, ability to reduce nitrate to nitrite and sensitivity to cephalothin. Complete 16S rRNA analysis of five of the nine strains characterised biochemically indicated that the organisms isolated were two novel Helicobacter spp. By electron microscopy, these novel helicobacters had spiral morphology with bipolar sheathed flagella. This is the first report describing the isolation of novel Helicobacter spp. from inflamed colons of rhesus monkeys. Studies are needed to determine whether these novel Helicobacter spp. play a causal role in the initiation and progression of chronic colitis in macaques. Further microbiological and histological analysis of this chronic idiopathic colitis syndrome in macaques may prove useful in understanding the aetiology and pathogenesis of inflammatory bowel disease in man.
慢性特发性弥漫性结肠炎是圈养恒河猴中一种公认的临床和病理实体。六只恒河猴被诊断患有临床上使人虚弱的慢性腹泻。组织学上,结肠组织的特征为慢性、中度至重度结肠炎和盲肠炎,固有层有弥漫性单核细胞炎症、反应性淋巴组织增生和多灶性微脓肿。对结肠组织进行沙门氏菌属和志贺氏菌属培养;所有结果均为阴性。样本中艰难梭菌A和B毒素检测为阴性,结肠组织抗酸菌特殊染色也为阴性。对六只腹泻猴子进行检测,其血清中针对B病毒、猴T淋巴细胞白血病病毒、猴逆转录病毒和猴免疫缺陷病毒的IgG抗体结果均为阴性。对来自同一猴群的六只腹泻猴子以及两只经组织学证实患有结肠炎的临床正常猴子的结肠组织也进行了微需氧培养。在37摄氏度和42摄氏度下对所有八只猴子的微需氧培养物在含抗生素培养基上均显示出针尖状或扩散性菌落。细菌被鉴定为革兰氏阴性、氧化酶阳性和脲酶阴性。在对九株菌株进行生化特征分析后,鉴定出两种不同的生物型(通过16S rRNA分析对应不同物种)。一种生物型(1型)来自非腹泻猴子,第二种生物型(2型)来自患有亚临床慢性结肠炎症的腹泻动物,二者在过氧化氢酶活性、将硝酸盐还原为亚硝酸盐的能力以及对头孢噻吩的敏感性方面存在差异。对九株经生化特征分析的菌株中的五株进行完整的16S rRNA分析表明,分离出的生物体是两种新型幽门螺杆菌。通过电子显微镜观察,这些新型幽门螺杆菌具有螺旋形态,带有双极鞘鞭毛。这是首次报道从恒河猴发炎的结肠中分离出新型幽门螺杆菌。需要开展研究以确定这些新型幽门螺杆菌是否在猕猴慢性结肠炎的起始和进展中起因果作用。对猕猴这种慢性特发性结肠炎综合征进行进一步的微生物学和组织学分析可能有助于理解人类炎症性肠病的病因和发病机制。