Amelioration of Central Nervous System Autoimmunity Through FFAR2 Agonism Is Associated With Changes in Gut Microbiota

• Published in: Brain and Behavior
• Main Authors: Bojan Jevtić, Goran Stegnjaić, Suzana Stanisavljević, Milica Lazarević, Filip Nikolić, Graeme L. Fraser, Đorđe Miljković, Mirjana Dimitrijević
• Format: Article
• Language: English
• Published: Wiley 2025-03-01
• Subjects: experimental autoimmune encephalomyelitis; free fatty acid receptor 2; gut microbiota; short‐chain fatty acids
• Online Access: https://doi.org/10.1002/brb3.70350

ABSTRACT Purpose: The intestinal immune compartment is increasingly recognized as an important player in central nervous system (CNS) autoimmunity. We have recently reported that oral administration of the free fatty acid receptor 2 (FFAR2) agonist Cpd1 in the inductive phase of experimental autoimmune encephalomyelitis (EAE) in rats ameliorates the disease by stimulating the regulatory immune response in the intestine. Method: Here, the effects of Cpd1 on the gut microbiota and short‐chain fatty acid (SCFA) composition were investigated in the same experimental system. Finding: Increased levels of the phylum Proteobacteria, the class Gammaproteobacteria, the orders Burkholderiales and Erysipelotrichales, the families Sutterellaceae and Erysipelotrichaceae, and the genera Parasutterella and Faecalibaculum were observed in agonist‐treated rats. The genera Allobaculum and Ileibacterium were only detected in the agonist‐treated group. The treatment led to changes in the functional profile of the gut microbiota both in the KEGG orthologous pathways and in the clusters of orthologous genes. In addition, an altered profile of intestinal SCFA content was observed in the agonist‐treated group. Conclusion: The effects of Cpd1 on the gut microbiota and SCFA composition are relevant to the observed treatment benefit of FFAR2 agonism in the EAE model during the inductive phase of the disease.