Gut microbiota and stroke: new avenues to improve prevention and outcome.

Abstract

Despite major recent therapeutic advances, stroke remains a leading cause of disability and death. Consequently, new therapeutic targets need to be found to improve stroke outcome. The deleterious role of gut microbiota alteration (often mentioned as "dysbiosis") on cardiovascular diseases, including stroke and its risk factors, has been increasingly recognized. Gut microbiota metabolites, such as Trimethylamine-N-Oxyde (TMAO), Short Chain Fatty Acid (SCFA), and tryptophan, play a key role. Evidence of a link between alteration of the gut microbiota and cardiovascular risk factors exists, with a possible causality link supported by several pre-clinical studies. Gut microbiota alteration also seems to be implicated at the acute phase of stroke, with observational studies showing more non-neurological complications, higher infarct size and worse clinical outcome in stroke patients with altered microbiota. Microbiota targeted strategies have been developed, including prebiotics/probiotics, fecal microbiota transplantation, SCFA and TMAO inhibitors. Research teams have been using different time windows and endpoint for their studies, with various results. Considering the available evidence, we believe that studies focusing on microbiota targeted strategies in association with conventional stroke care should be conducted. Such strategies should be considered according to three therapeutic time windows: first, at the pre-stroke (primary prevention) or post-stroke (secondary prevention) phases, to enhance the control of cardiovascular risk factors. Secondly, at the acute phase of stroke, to limit the infarct size and the systemic complications and enhance the overall clinical outcome. Thirdly, at the subacute phase of stroke, to prevent stroke recurrence and promote neurological recovery.