A gut bacterial compound may worsen stroke brain injury by influencing immune responses, research in mice suggests.
After severe stroke, mice had higher levels of gut bacteria able to produce indole, a compound made from the amino acid tryptophan.
Researchers found that indole-producing bacteria worsened brain injury in mice. In people with ischaemic stroke, higher bacterial TnaA abundance was associated with poorer functional outcomes.
The research was led by a team at the Institute for Stroke and Dementia Research at LMU Klinikum.
Dr Rosa Delgado Jiménez, who shares first authorship with Alexandria Ruggles and Mujeeb Adedokun, said: “Dendritic cells have long extensions, like arms, that allow them to sense changes in their environment, including metabolites produced by gut bacteria.
“When we switched off AHR, the behaviour of these cells changed completely: Dendritic cells were better able to migrate from the intestine to the meninges, the membranes surrounding the brain.
“These dendritic cells also promoted protective T cells and helped reduce the damage in the brain.”
The bacteria carry a gene called tnaA, which enables them to convert tryptophan from food into indole.
Researchers found that indole acts on a receptor called AHR, or aryl hydrocarbon receptor, in dendritic cells, immune cells that monitor the intestinal lining and help coordinate immune responses.
When AHR was switched off specifically in dendritic cells, mice were better protected against brain injury following stroke.
The researchers also found evidence that the pathway may be relevant in people with ischaemic stroke.
Higher bacterial TnaA abundance was associated with poorer functional outcomes. Bacteria carrying the tnaA gene were also more abundant in people with stroke risk factors including obesity and type 2 diabetes.
Researchers said they still need to determine whether the mechanism identified in mice also occurs in people.
Delgado Jiménez said: “We usually think of stroke as an injury restricted to the brain, but our findings show that the gut can help shape the immune response to that injury.”
Dr Corinne Benakis, who led the research, said: “We still need to determine whether the mechanism we identified in mice also occurs in patients, but our findings open new avenues for investigating whether the gut microbiota could eventually be targeted to improve stroke outcome, including through preventive approaches in people at increased risk of stroke.”
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