2026-09-30 ミュンヘン大学（LMU）
＜関連情報＞
- https://www.lmu.de/en/newsroom/news-overview/news/how-gut-bacteria-can-shape-the-brains-response-to-stroke-c50ea30e.html
- https://www.cell.com/cell/fulltext/S0092-8674(26)01115-3
腸内細菌叢は腸管樹状細胞のAHRを介して脳卒中の重症度を誘発する Gut microbiota primes stroke severity via the AHR in intestinal dendritic cells
Rosa Delgado Jiménez ∙ Alexandria Ruggles ∙ Mujeeb Adekunle Adedokun ∙ … ∙ Michael Delacher, ∙ Arthur Liesz ∙ Corinne Benakis
Cell Published:September 29, 2026
DOI:https://doi.org/10.1016/j.cell.2026.09.013
Highlights
- Microbial indole worsens stroke through AHR signaling in DCs
- AHR loss promotes regulatory and migratory programs in intestinal DCs
- AHR inhibition enhances gut-derived DC trafficking to the meninges
- tnaA-encoding bacteria are associated with poor outcomes in patients with stroke
Summary
The gut microbiota modulates systemic immunity and neurological diseases, yet the underlying mechanisms remain unclear. Here, we identify the enrichment of indole-producing Escherichia coli being associated with worse outcomes in mice and patients with ischemic stroke. Microbial indole triggers an aryl hydrocarbon receptor (AHR)-dependent response in dendritic cells (DCs). DC-specific AHR deletion improves stroke outcomes and preserves intestinal conventional type 1 DCs. AHR deletion also promotes immunoregulatory and migratory transcriptional signatures and enhances CCR7-dependent migration in vitro. Pharmacological AHR inhibition favors gut-derived DC accumulation in the meninges, accompanied by increased regulatory T cells (Tregs) and reduced neuroinflammation, while Treg depletion abolishes the neuroprotection conferred by AHR inhibition. Detrimental effects of indole-producing Escherichia coli, indole administration, and microbiota transplantation from patients with stroke are attenuated in DC-specific AHR-deficient mice. These findings define a microbiota-AHR axis that programs intestinal immune responses before brain injury and highlight microbial tryptophan metabolism as a tractable therapeutic target.
