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

被引：0

作者：

Peesh, Pedram ^{[1
,2
,3
]}

Blasco-Conesa, Maria P. ^{[1
]}

El Hamamy, Ahmad ^{[1
]}

Khan, Romeesa ^{[1
]}

Guzman, Gary U. ^{[1
]}

Honarpisheh, Parisa ^{[1
]}

Mohan, Eric C. ^{[1
]}

Goodman, Grant W. ^{[1
]}

Nguyen, Justin N. ^{[1
]}

Banerjee, Anik ^{[1
,2
]}

West, Bryce E. ^{[1
]}

Ko, Kyung Ae ^{[1
]}

Korf, Janelle M. ^{[1
,2
]}

Tan, Chunfeng ^{[1
]}

Fan, Huihui ^{[1
]}

Colpo, Gabriela D. ^{[1
]}

Ahnstedt, Hilda ^{[1
]}

Couture, Lucy ^{[1
]}

Roh, Solji ^{[1
]}

Kofler, Julia K. ^{[4
]}

Moruno-Manchon, Jose F. ^{[1
]}

Maniskas, Michael E. ^{[1
]}

Aronowski, Jaroslaw ^{[1
]}

Ritzel, Rodney M. ^{[1
]}

Lee, Juneyoung ^{[1
]}

Li, Jun ^{[1
]}

Bryan, Robert M. ^{[5
]}

Chauhan, Anjali ^{[1
]}

Venna, Venugopal Reddy ^{[1
]}

Mccullough, Louise D. ^{[1
]}

Ganesh, Bhanu Priya ^{[1
,2
]}

机构：

[1] Univ Texas Houston, McGovern Med Sch, Dept Neurol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson UTHlth, Grad Sch Biomed Sci, Houston, TX 77030 USA

[3] Univ Texas Houston, McGovern Med Sch, Dept Neurosurg, Houston, TX USA

[4] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA

[5] Baylor Coll Med, Dept Anesthesiol, Houston, TX USA

来源：

NATURE COMMUNICATIONS | 2025年 / 16卷 / 01期

关键词：

INTESTINAL MICROBIOTA; TRYPTOPHAN-METABOLISM; ISCHEMIC-STROKE; INDOLE; SERUM; ACTIVATION; GREENGENES; HEALTH;

D O I：

10.1038/s41467-025-57014-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

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