Salt-sensitive alterations in gut microbiota impact Th17 cells and neuroinflammation (P3.391)

Objective: To examine the influence of high salt concentrations on the gut microbiome, the immune system and its implications for neuroinflammation. Background: We have demonstrated that high salt concentrations drive autoimmunity by the induction of pathogenic Th17 cells. Furthermore, the importance of the gut microbiome for multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) has recently been recognized. Yet, the effect of high salt on the gut microbiome is still unknown. Design/Methods: We analyzed fecal pellets from normal salt diet (NSD) or high-salt diet (HSD)-fed mice by 16S ribosomal RNA gene sequencing and AdaBoost classifier. In addition, ex vivo experiments in myelin oligodendrocyte glycoprotein induced EAE were performed to analyze spinal cord, spleen and intestine by flow cytometry. Results: HSD feeding resulted in a 1.9-fold higher fecal sodium concentration compared to feces of NSD-fed mice. This increase altered the fecal microbiome, particularly by depleting Lactobacillus murinus . Exacerbated disease course due to HSD feeding was prevented by concomitant treatment with L. murinus (EAE scores HSD: 3.1 ± 0.15; NSD: 2.1 ± 0.31; HSD + L. murinus : 1.6 ± 0.37; n=6–11, p L. murinus . At the maximum of disease, flow cytometry analysis of splenocytes and spinal cord infiltrating lymphocytes revealed a significant reduction of Th17 cell frequencies by L. murinus treatment compared to HSD feeding alone. mRNA expression analysis of spinal cord tissue confirmed the decreased infiltration of Th17 cells after L. murinus treatment. Conclusions: Our results link the detrimental effects of high salt consumption to the gut-immune axis and highlight the gut microbiome as a new therapeutic target to counteract the salt-sensitive pathology in neuroinflammation. Disclosure: Dr. Linker has received personal compensation for activities with Bayer, Biogen, Genzyme, MerckSerono,Novartis Pharma Roche Pharma, and TEVA Pharma. Dr. Joerg has nothing to disclose. Dr. Wilck has nothing to disclose. Dr. Matus has nothing to disclose. Dr. Kearney has nothing to disclose. Dr. Olesen has nothing to disclose. Dr. Kleinewietfeld has nothing to disclose. Dr. Alm has nothing to disclose. Dr. Mueller has nothing to disclose.