Cognitive impairment is increasingly recognized as a multifactorial neurological condition involving gut microbiota imbalance, impaired barrier function, neuroinflammatory activation, and disrupted synaptic plasticity. However, the molecular mechanisms that integrate these pathological events remain largely unclear. The RhoA/ROCK signaling pathway, a key regulator of actin cytoskeleton remodeling, intercellular junction dynamics, barrier permeability, inflammatory signaling, and neuronal structural plasticity, may represent a potential molecular interface connecting intestinal microbial disturbances with cognitive dysfunction. Accumulating evidence suggests that alterations in gut microbiota composition, microbiota-derived metabolites, and inflammation-related microbial signals can modulate RhoA/ROCK activity, thereby affecting intestinal barrier integrity and blood-brain barrier function, regulating systemic and neuroinflammatory responses, and influencing cognition-related processes, including synaptic remodeling, axonal guidance, and long-term potentiation. Nevertheless, the biological consequences of RhoA/ROCK activation are highly dependent on cellular and pathological contexts. Transient and spatially restricted activation may contribute to barrier restoration and synaptic maintenance, whereas persistent or excessive activation may promote barrier disruption and neuronal dysfunction. Although current evidence remains largely preclinical and heterogeneous, RhoA/ROCK signaling provides a potential mechanistic framework for understanding microbiota-gut-brain interactions in cognitive disorders. Further investigations are required to establish causal relationships and clarify its therapeutic relevance.
