Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδT cells

By Corinne Benakis, D. Brea, S. Caballero, G. Faraco, Jamie M. Moore, Michelle Murphy, G. Sita, Gianfranco Racchumi, Lilan Ling, Eric G. Pamer and 2 more. Nature Medicine, 2016

930 citations recorded by the source corpus.

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.

Subfields: Biological Psychiatry, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/2e4631db78e2a2ceeac409390edfeca14dcca84c

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Citations in the corpus

Ischemia/Reperfusion (2016, neutral): “(63) showed that intestinal bacteria participate in the trafficking of effector T cells from the small intestine to the leptomeninges in the brain where they”
The Central Nervous System and the Gut Microbiome (2016, background): “Notably, CXCL1 expression was shown to be differentially induced in the brains of an ischemic stroke mouse model, in mice with different microbiotas, suggesting a potential role during homeostasis and development, although further investigation is needed (Benakis et al., 2016).”
Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke (2016, background): “…could determine in a cell-tracking experiment from intestinal PPs to the ischemic brain that at least one-fourth of all brain-invading T cells within the acute phase after stroke are derived from the intestinal immune compartment, which is consistent with a previous report (Benakis et al., 2016).”
Inflammation and Stroke: An Overview (2016, background): “[75] showed that treatment of mice with amoxicillin increased Tregs and suppressed IL17γδT in the small intestine, which correlated with smaller infarcts and better behavioral outcome after transient MCA occlusion, an effect that could be transferred by fecal matter transplants [75].”
Immune responses to stroke: mechanisms, modulation, and therapeutic potential. (2020, background): “Accordingly, natural IL-17– secreting γδ T cells contribute to ischemic injury by inhibiting neutrophil infiltration (53, 85, 89, 90).”
The IL-17 family of cytokines in health and disease (2019, background): “Increased generation of IL-17-producing T cells during intestinal dysbiosis exacerbates central nervous system (CNS)-targeted autoimmune disease (Kumar et al., 2016) and impairs recovery following brain ischemia (stroke) (Benakis et al., 2016).”
Neurotransmitter modulation by the gut microbiota (2018, background): “…Palma et al., 2017), Parkinson’s Disease (Sampson et al., 2016), Alzheimer’s Disease (Minter et al., 2016), Multiple Sclerosis (MS) (Berer et al., 2017; Cekanaviciute et al., 2017), ischemic stroke (Benakis et al., 2016), and symptomologies of Autism Spectrum Disorder (ASD) (Hsiao et al., 2013).”