Bacterial lipodipeptide, Lipid 654, is a microbiome‐associated biomarker for multiple sclerosis

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. Multiple sclerosis: Seeking an early warning of autoimmunity A molecule secreted by gut microbes may improve the diagnosis of multiple sclerosis (MS) and offer a window into the roots of this autoimmune disorder. Although broadly understood as a disease in which genes and environment interact resulting in the body attacking its own nervous system, scientists know little about the causes of MS or the environmental factors involved in its onset. However, a team led by Robert Clark at the University of Connecticut Health Center has discovered a molecule produced by human commensal bacteria that may offer both a clue to relevant environmental factors and a useful diagnostic tool. The researchers determined that the molecule, termed ‘lipid 654’, was consistently found at greatly reduced levels in the blood of MS patients relative to healthy individuals or patients with an unrelated neurological disorder. Furthermore, as lipid 654 specifically binds to an impo