Bacterial lipodipeptide, Lipid 654, is a microbiome-associated biomarker for multiple sclerosis.
Bacterial lipodipeptide, Lipid 654, is a microbiome-associated biomarker for multiple sclerosis.
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DOI：
10.1038/cti.2013.11
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发表时间：
2013-11
影响因子：
5.8
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多发性硬化（MS）是一种病因不明的自身免疫性疾病。感染性病原体已被认为是MS中的环境因素，但这一概念仍有争议。最近，胃肠道肠道细菌已被牵连在自身免疫性疾病的发病机制，但人类全身性自身免疫与肠道微生物组的关系的机制尚未确定。与缺乏对MS的致病机制和相关环境因素的了解相一致，尚未鉴定出区分MS患者与健康个体的血液生物标志物。我们最近发现了一种独特的胃肠道和口腔细菌衍生的脂二肽，脂质654，它是由肠道细菌产生的，作为人类和小鼠Toll样受体2配体。使用多反应监测质谱，靶向脂质组学的关键方法，我们现在报告可以在健康个体的血清中回收脂质654。最有趣的是，我们发现脂质654在MS患者血清中的表达水平显著低于健康个体和阿尔茨海默病患者。因此，这些结果首次确定了胃肠道和口腔肠道微生物组与人类系统性自身免疫性疾病相关的潜在机制。此外，这些结果还确定了MS的潜在病因环境因素和新的临床相关血清生物标志物。
Multiple sclerosis (MS) is an autoimmune disease of unknown etiology. Infectious agents have been suggested to have a role as environmental factors in MS, but this concept remains controversial. Recently, gastrointestinal commensal bacteria have been implicated in the pathogenesis of autoimmune diseases, but mechanisms underlying the relationship of human systemic autoimmunity with the commensal microbiome have yet to be identified. Consistent with the lack of understanding of pathogenic mechanisms and relevant environmental factors in MS, no blood biomarkers have been identified that distinguish MS patients from healthy individuals. We recently identified a unique gastrointestinal and oral bacteria-derived lipodipeptide, Lipid 654, which is produced by commensal bacteria and functions as a human and mouse Toll-like receptor 2 ligand. Using multiple-reaction-monitoring mass spectrometry, a critical approach in targeted lipidomics, we now report that Lipid 654 can be recovered in the serum of healthy individuals. Most interestingly, we find that Lipid 654 is expressed at significantly lower levels in the serum of patients with MS compared with both healthy individuals and patients with Alzheimer's disease. These results thus identify for the first time a potential mechanism relating the gastrointestinal and oral commensal microbiome to a human systemic autoimmune disease. In addition, these results also identify a potential etiologic environmental factor and novel clinically relevant serum biomarker for MS.