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Fecal Lcn-2 level is a sensitive biological indicator for gut dysbiosis and intestinal inflammation in multiple sclerosis
In this study by Yadav et al. (2022), the authors investigated the mechanisms linking Multiple Sclerosis (MS) with gastrointestinal inflammation and derangements of the gut microbiome. Humanized transgenic (Tg) HLA-DR2a and human T cell receptor (TCR) specific for myelin basic protein peptide (MBP87-99)/HLA-DR2a were examined for signs of gastrointestinal inflammation (immune cell infiltration) during the course of developing spontaneous experimental autoimmune encephalomyelitis (EAE). Sample analysis revealed concurrent EAE and colitis in mice, with a substantial neutrophilic and MBP-specific Th17 cellular infiltration, demonstrating a relationship between intestinal inflammation and central nervous system (CNS) autoimmune diseases. In addition, the mice were found to demonstrate substantially elevated levels of Fecal Lcn-2 (Lcn-2), a neutrophil-related marker of intestinal inflammation. Upon comparison to healthy donors (HDs), the authors noted that human MS patients demonstrated elevated levels of neutrophil-related markers of intestinal inflammation, including neutrophil elastase, calprotectin, and Lcn-2, which was also related to microbiome dysbiosis, in particular, a reduction in the populations of Roseburia, Anaerobutyricum, and Blautia, which have been shown to enhance inflammatory bowel disease (IBD) status. Of note, reductions in Blautia massiliensis and a rise in Fecal Lcn-2 led to a reduction in serum acetate levels (short-chain fatty acid, functioning in lipogenesis and energy production) in MS patients compared to HDs. The authors conclude that intestinal inflammation and microbiome derangements are linked to infiltration with neutrophils and Th17 cells and that fecal Lcn-2 can be utilized as a sensitive marker for microbiome derangements in MS patients. [NPID: Biomarker, colitis, experimental autoimmune encephalomyelitis, EAE, gut dysbiosis, lipocalin 2, LCN 2, multiple sclerosis, neutrophils]
Year: 2022
