The Potential Mediation of the Effects of Physical Activity on Cognitive Function by the Gut Microbiome

The population of older adults is growing dramatically worldwide. As older adults are at greater risk of developing disorders associated with cognitive dysfunction (i.e., dementia), healthcare costs are expected to double by 2040. Evidence suggests dementia may be slowed or prevented by lifestyle interventions, including physical activity (PA). PA is associated with improved cognitive function and may reduce risk for dementia by mitigating known risk factors (i.e., cardiovascular diseases) and/or by enhancing neurochemical processes. An emerging area of research suggests the gut microbiome may have similar neuroprotective effects. Altering the gut microbiome has been found to target physiological processes associated with dementia risk, and it influences gut-brain-microbiome axis signaling, impacting cognitive functioning. The gut microbiome can be altered by several means (i.e., disease, diet, prebiotics, probiotics), including PA. As PA and the gut microbiome independently influence cognitive function and PA changes the composition of the gut microbiome, cognitive improvement due to PA may be partially mediated by the gut microbiome. The present article provides an overview of the literature regarding the complex associations among PA, cognitive function, and the gut microbiome, as well as their underlying biological mechanisms. A comprehensive, theoretical model integrating evidence for the potential mediation is proposed.