Potential synergistic effects of exercise and gut microbiota on post-stroke recovery: mechanistic insights and a proposed stage-specific research framework

Abstract

Post-stroke motor dysfunction imposes a profound burden on long-term quality of life. While conventional rehabilitation facilitates neuroplasticity, the marked interindividual variability in functional outcomes underscores the critical necessity for novel, synergistic adjuncts. Emerging evidence suggests that microbiota-related pathways may influence rehabilitation responsiveness; however, whether deliberate microbiota modification improves motor recovery remains uncertain. This narrative review summarizes evidence suggesting associations between post-stroke gut dysbiosis and motor outcomes, and integrates reported mechanistic pathways across barrier, immune, and metabolic domains to inform a phase-stratified exercise–microbiota framework for future trials. Stroke induces systemic disturbances that affect the intestinal barrier, immune regulation, and metabolic homeostasis. These perturbations are frequently accompanied by reduced abundance of short-chain fatty acid-producing taxa and altered neurotrophic signaling, changes that may constrain the neuroplastic milieu. Concurrently, structured exercise interventions have been demonstrated to remodel the gut ecosystem and modulate the systemic inflammatory milieu. In this context, microbiome-derived metabolites may function as signaling mediators that facilitate crosstalk among barrier integrity, immune regulation, and neural plasticity networks. Synthesizing these mechanistic insights, we propose a comprehensive framework that prioritizes the preservation of intestinal barrier integrity alongside titrated mobilization during the acute phase. Overall, combined interventions targeting exercise and the gut microbiota are biologically plausible and potentially feasible in stroke rehabilitation. While current evidence is promising, it remains nascent. Rigorous, phase-specific randomized controlled trials are imperative to confirm efficacy, define optimal dosing, and enable precision implementation.