Feil Family Brain & Mind Research Institute

You are here

Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells.

TitleCommensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsBenakis C, Brea D, Caballero S, Faraco G, Moore J, Murphy M, Sita G, Racchumi G, Ling L, Pamer EG, Iadecola C, Anrather J
JournalNat Med
Volume22
Issue5
Pagination516-23
Date Published2016 05
ISSN1546-170X
KeywordsAnimals, Anti-Bacterial Agents, Behavior, Animal, Blood-Brain Barrier, Brain, Brain Ischemia, Dendritic Cells, Dysbiosis, Fecal Microbiota Transplantation, Flow Cytometry, Gastrointestinal Microbiome, Immunity, Mucosal, Immunohistochemistry, Infarction, Middle Cerebral Artery, Interleukin-10, Interleukin-17, Intestinal Mucosa, Intestine, Small, Intestines, Leukocytes, Lymphocytes, Mice, Receptors, Antigen, T-Cell, gamma-delta, RNA, Messenger, RNA, Ribosomal, 16S, Stroke, T-Lymphocytes, T-Lymphocytes, Regulatory
Abstract

Commensal gut bacteria impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the microbiota has an impact on the outcome of acute brain injury. Here we show that antibiotic-induced alterations in the intestinal flora reduce ischemic brain injury in mice, an effect transmissible by fecal transplants. Intestinal dysbiosis alters immune homeostasis in the small intestine, leading to an increase in regulatory T cells and a reduction in interleukin (IL)-17-positive γδ T cells through altered dendritic cell activity. Dysbiosis suppresses trafficking of effector T cells from the gut to the leptomeninges after stroke. Additionally, IL-10 and IL-17 are required for the neuroprotection afforded by intestinal dysbiosis. The findings reveal a previously unrecognized gut-brain axis and an impact of the intestinal flora and meningeal IL-17(+) γδ T cells on ischemic injury.

DOI10.1038/nm.4068
Alternate JournalNat. Med.
PubMed ID27019327
PubMed Central IDPMC4860105
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
R01 NS081179 / NS / NINDS NIH HHS / United States
R01 NS034179 / NS / NINDS NIH HHS / United States