Vieira S M, Pagovich O E, Kriegel M A
1Department of Immunobiology.
Lupus. 2014 May;23(6):518-26. doi: 10.1177/0961203313501401.
There is growing evidence that the commensal bacteria in the gastrointestinal tract (the gut microbiota) influence the development of autoimmunity in rodent models. Since humans have co-evolved with commensals for millennia, it is likely that people, who are genetically predisposed to autoimmunity, harbor gut microbial communities that similarly influence the onset and/or severity of disease. Beyond the current efforts to identify such disease-promoting or -preventing commensals ("pathobionts" or "symbionts"), it will be important to determine what factors modulate them. Dietary changes are known to affect both the composition and function of the gut microbial communities, which in turn can alter the innate and adaptive immune system. In this review, we focus on the relationships between diet, microbiota, and autoimmune diseases. We hypothesize that the beneficial and life-prolonging effects of caloric restriction on a variety of autoimmune models including lupus might partly be mediated by its effects on the gut microbiome and associated virome, the collection of all viruses in the gut. We give recent examples of the immunomodulatory potential of select gut commensals and their products or diet-derived metabolites in murine models of arthritis, multiple sclerosis, and type 1 diabetes. Lastly, we summarize the published phenotypes of germ-free mouse models of lupus and speculate on any role of the diet-sensitive microbiome and virome in systemic lupus and the related antiphospholipid syndrome.
越来越多的证据表明,胃肠道中的共生细菌(肠道微生物群)会影响啮齿动物模型中自身免疫性疾病的发展。由于人类与共生菌已经共同进化了数千年,因此,那些具有自身免疫性疾病遗传易感性的人,其肠道微生物群落可能同样会影响疾病的发作和/或严重程度。除了目前识别此类促进或预防疾病的共生菌(“致病共生菌”或“共生菌”)的努力之外,确定调节它们的因素也很重要。已知饮食变化会影响肠道微生物群落的组成和功能,进而改变先天免疫系统和适应性免疫系统。在这篇综述中,我们重点关注饮食、微生物群和自身免疫性疾病之间的关系。我们假设,热量限制对包括狼疮在内的多种自身免疫模型的有益和延长寿命的作用,可能部分是由其对肠道微生物组和相关病毒组(肠道中所有病毒的集合)的影响介导的。我们列举了近期在关节炎、多发性硬化症和1型糖尿病小鼠模型中,特定肠道共生菌及其产物或饮食衍生代谢物的免疫调节潜力的例子。最后,我们总结了已发表的狼疮无菌小鼠模型的表型,并推测饮食敏感的微生物组和病毒组在系统性红斑狼疮及相关抗磷脂综合征中的作用。