Agrawal Gaurav, Borody Thomas J, Aitken John M
Division of Diabetes & Nutritional Sciences, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
, Sydney, Australia.
Dig Dis Sci. 2024 Jul;69(7):2289-2303. doi: 10.1007/s10620-024-08508-4. Epub 2024 Jun 19.
Mycobacterium avium ssp. paratuberculosis (MAP) has been implicated in the development of Crohn's disease (CD) for over a century. Similarities have been noted between the (histo)pathological presentation of MAP in ruminants, termed Johne's disease (JD), and appearances in humans with CD. Analyses of disease presentation and pathology suggest a multi-step process occurs that consists of MAP infection, dysbiosis of the gut microbiome, and dietary influences. Each step has a role in the disease development and requires a better understanding to implementing combination therapies, such as antibiotics, vaccination, faecal microbiota transplants (FMT) and dietary plans. To optimise responses, each must be tailored directly to the activity of MAP, otherwise therapies are open to interpretation without microbiological evidence that the organism is present and has been influenced. Microscopy and histopathology enables studies of the mycobacterium in situ and how the associated disease processes manifest in the patient e.g., granulomas, fissuring, etc. The challenge for researchers has been to prove the relationship between MAP and CD with available laboratory tests and methodologies, such as polymerase chain reaction (PCR), MAP-associated DNA sequences and bacteriological culture investigations. These have, so far, been inconclusive in revealing the relationship of MAP in patients with CD. Improved and accurate methods of detection will add to evidence for an infectious aetiology of CD. Specifically, if the bacterial pathogen can be isolated, identified and cultivated, then causal relationships to disease can be confirmed, especially if it is present in human gut tissue. This review discusses how MAP may cause the inflammation seen in CD by relating its known pathogenesis in cattle, and from examples of other mycobacterial infections in humans, and how this would impact upon the difficulties with diagnostic tests for the organism.
鸟分枝杆菌副结核亚种（MAP）与克罗恩病（CD）的发病关联已逾一个多世纪。人们注意到，反刍动物中由MAP引起的（组织）病理学表现（称为副结核病，JD）与CD患者的表现存在相似之处。对疾病表现和病理学的分析表明，发病过程分多步，包括MAP感染、肠道微生物群失调和饮食影响。每一步都在疾病发展中起作用，要实施抗生素、疫苗接种、粪便微生物群移植（FMT）和饮食计划等联合疗法，就需要对此有更深入的了解。为优化治疗反应，每种疗法都必须直接针对MAP的活性进行调整，否则在没有微生物学证据证明该病原体存在且受到影响的情况下，这些疗法的效果难以评估。显微镜检查和组织病理学可用于原位研究分枝杆菌，以及相关疾病过程在患者体内的表现，如肉芽肿、裂隙等。研究人员面临的挑战是，利用聚合酶链反应（PCR）、MAP相关DNA序列和细菌培养研究等现有实验室检测方法和技术，证明MAP与CD之间的关系。到目前为止，这些方法在揭示MAP与CD患者之间的关系方面尚无定论。改进且准确的检测方法将为CD的感染性病因提供更多证据。具体而言，如果能分离、鉴定和培养这种细菌病原体，就能确认其与疾病的因果关系，尤其是当它存在于人体肠道组织中时。本综述通过阐述MAP在牛体内已知的发病机制，以及人类其他分枝杆菌感染的实例，探讨了MAP如何导致CD中出现的炎症，以及这将如何影响该病原体诊断检测的难点。
