Short-chain fatty acids suppresses astrocyte activation by amplifying Trp-AhR-AQP4 signaling in experimental autoimmune encephalomyelitis mice

• DOI: 10.1007/s00018-024-05332-x
• Publication Date: 2024-07-08T13:02:00Z
• Authors: Xiuli Lin; Yufeng Peng; Zhimei Guo; Wuhui He; Wenyuan Guo; Junmin Feng; Lin Lu; Qin Liu; Pingyi Xu
• Keywords: Aquaporin 4; Encephalomyelitis

The function of astrocytes in response to gut microbiota-derived signals has an important role the pathophysiological processes central nervous system (CNS) diseases. However, specific effects metabolites on astrocyte activation have not been elucidated yet. Experimental autoimmune encephalomyelitis (EAE) was induced female C57BL/6 mice as a classical MS model. alterations microbiota and levels short-chain fatty acids (SCFAs) were assessed after EAE induction. We observed that exhibit low Allobaculum, Clostridium_IV, Clostridium_XlVb, Lactobacillus genera, microbial-derived SCFAs metabolites. supplementation suppressed by increasing level tryptophan (Trp)-derived AhR ligands activating AhR. beneficial clinical scores, histopathological alterations, blood brain barrier (BBB)-glymphatic abolished intracisterna magna injection AAV-GFAP-shAhR. Moreover, loss AQP4 polarity within AhR-dependent manner. Together, potentially suppresses amplifying Trp-AhR-AQP4 signaling mice. Our study demonstrates may serve viable therapy for inflammatory disorders CNS.