Benefits of equilibrium between microbiota- and host-derived ligands of the aryl hydrocarbon receptor after stroke in aged male mice.

• Tác giả: Hilda Ahnstedt, Jaroslaw Aronowski, Anik Banerjee, Maria P Blasco-Conesa, Robert M Bryan, Anjali Chauhan, Gabriela D Colpo, Lucy Couture, Ahmad El Hamamy, Huihui Fan, Bhanu Priya Ganesh, Grant W Goodman, Gary U Guzman, Parisa Honarpisheh, Romeesa Khan, Kyung Ae Ko, Julia K Kofler, Janelle M Korf, Juneyoung Lee, Jun Li, Michael E Maniskas, Louise D McCullough, Eric C Mohan, Jose F Moruno-Manchon, Justin N Nguyen, Pedram Peesh, Rodney M Ritzel, Solji Roh, Chunfeng Tan, Venugopal Reddy Venna, Bryce E West
• Ngôn ngữ: eng
• Ký hiệu phân loại: 331.255 Fringe benefits
• Thông tin xuất bản: England : Nature communications , 2025
• Bộ sưu tập: NCBI
• ID: 469316

Tóm tắt

Recent studies have highlighted the crucial role of microglia (MG) and their interactions with the gut microbiome in post-stroke neuroinflammation. The activation of immunoregulatory pathways, including the aryl hydrocarbon receptor (AHR) pathway, is influenced by a dynamic balance of ligands derived from both the host and microbiota. This study aimed to investigate the association between stroke-induced dysbiosis and the resultant imbalance in AHR ligand sources (loss of microbiota-derived [indole-based] and increase of host-derived [kynurenine-based]) after stroke. Microbiota-derived AHR ligands decreased in human plasma and remained low for days following an ischemic stroke highlighting the translational significance. Transient-middle-cerebral-artery-occlusion was performed in aged wild-type and germ-free male mice. MG-AHR expression and activity increased in both in vivo and ex vivo stroke models. Germ-free mice showed altered neuroinflammation and antigen presentation while aged mice showed reduced infarct volume and neurological deficits following treatment with microbiota-derived AHR ligands after stroke. Restoring a balanced pool of host- and microbiota-derived AHR ligands may be beneficial after stroke and may represent a therapeutic target.