Rashed Reem, Valcheva Rosica, Dieleman Levinus A
Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Front Med (Lausanne). 2022 Jun 16;9:887044. doi: 10.3389/fmed.2022.887044. eCollection 2022.
Crohn's disease (CD) is an inflammatory bowel disease (IBD) sub-type characterized by transmural chronic inflammation of the gastrointestinal tract. Research indicates a complex CD etiology involving genetic predisposition and immune dysregulation in response to environmental triggers. The chronic mucosal inflammation has been associated with a dysregulated state, or dysbiosis, of the gut microbiome (bacteria), mycobiome (fungi), virome (bacteriophages and viruses), and archeaome (archaea) further affecting the interkingdom syntrophic relationships and host metabolism. Microbiota dysbiosis in CD is largely described by an increase in facultative anaerobic pathobionts at the expense of strict anaerobic Firmicutes, such as . In the mycobiome, reduced fungal diversity and fungal-bacteria interactions, along with a significantly increased abundance of spp. and a decrease in are well documented. Virome analysis also indicates a significant decrease in phage diversity, but an overall increase in phages infecting bacterial groups associated with intestinal inflammation. Finally, an increase in methanogenic archaea such as exhibits high immunogenic potential and is associated with CD etiology. Common anti-inflammatory medications used in CD management (amino-salicylates, immunomodulators, and biologics) could also directly or indirectly affect the gut microbiome in CD. Other medications often used concomitantly in IBD, such as antibiotics, antidepressants, oral contraceptives, opioids, and proton pump inhibitors, have shown to alter the gut microbiota and account for increased susceptibility to disease onset or worsening of disease progression. In contrast, some environmental modifications through alternative therapies including fecal microbiota transplant (FMT), diet and dietary supplements with prebiotics, probiotics, and synbiotics have shown potential protective effects by reversing microbiota dysbiosis or by directly promoting beneficial microbes, together with minimal long-term adverse effects. In this review, we discuss the different approaches to modulating the global consortium of bacteria, fungi, viruses, and archaea in patients with CD through therapies that include antibiotics, probiotics, prebiotics, synbiotics, personalized diets, and FMT. We hope to provide evidence to encourage clinicians and researchers to incorporate these therapies into CD treatment options, along with making them aware of the limitations of these therapies, and indicate where more research is needed.
克罗恩病（CD）是一种炎症性肠病（IBD）亚型，其特征为胃肠道的透壁性慢性炎症。研究表明，CD的病因复杂，涉及遗传易感性以及对环境触发因素的免疫失调。慢性黏膜炎症与肠道微生物群（细菌）、真菌微生物群（真菌）、病毒微生物群（噬菌体和病毒）以及古菌微生物群（古菌）的失调状态或生态失调有关，这进一步影响了跨界共生关系和宿主代谢。CD中的微生物群失调主要表现为兼性厌氧致病共生菌增多，而严格厌氧的厚壁菌门减少，如 。在真菌微生物群中，真菌多样性和真菌 - 细菌相互作用减少，以及 属的丰度显著增加和 减少，这些都有充分的文献记载。病毒微生物群分析还表明噬菌体多样性显著降低，但感染与肠道炎症相关细菌群的噬菌体总体增加。最后，产甲烷古菌如 的增加具有高免疫原性潜力，并与CD病因有关。CD治疗中常用的抗炎药物（氨基水杨酸类、免疫调节剂和生物制剂）也可能直接或间接影响CD患者的肠道微生物群。IBD中经常同时使用的其他药物，如抗生素、抗抑郁药、口服避孕药、阿片类药物和质子泵抑制剂，已显示会改变肠道微生物群，并导致疾病易感性增加或疾病进展恶化。相比之下，通过包括粪便微生物群移植（FMT）、饮食以及含有益生元、益生菌和合生元的膳食补充剂等替代疗法进行的一些环境调节，已显示出通过逆转微生物群失调或直接促进有益微生物而具有潜在的保护作用，且长期不良反应最小。在本综述中，我们讨论了通过包括抗生素、益生菌、益生元、合生元、个性化饮食和FMT等疗法来调节CD患者中细菌、真菌、病毒和古菌的全球群落的不同方法。我们希望提供证据，鼓励临床医生和研究人员将这些疗法纳入CD治疗方案，同时让他们了解这些疗法的局限性，并指出哪些方面需要更多研究。
