The Effects of Exercise on Gut Bacteria, Mood and Cognition in Depression

This study aims to investigate the effects of a 12-week aerobic (cardio) exercise intervention in people with Major Depressive Disorder. Measurements taken before, during, and following the 12-week intervention will include assessments of cognition, cardiorespiratory fitness, stress, mood and emotion, and gut bacteria.

Major depressive disorder (MDD) affects 10% of people globally. Additionally, approximately only half of individuals respond to current psychotherapy treatments, with approximately 30% of individuals classed as treatment resistant to psychopharmacological treatments. Despite the current variety in treatments, the gap in efficacy of current treatments means it is imperative to develop a deeper understanding of MDD, so additional treatment options are available to help those whose current treatment is ineffective. Apart from psychotherapies or combined psychopharmacotherapies, exercise may be beneficial for individuals with MDD. The microbiota-gut-brain-axis has been implicated in MDD, with gut bacteria relative abundance differences observed between individuals with MDD and healthy controls. Exercise interventions can reduce depressive symptoms in individuals with mild-moderate MDD and may be beneficial to people alongside standard care. Physical activity is also capable of modulating the gut microbiome. However, it remains an open question if lifestyle interventions such as exercise may act through the microbiome to enact positive outcomes in individuals with MDD. As depression does not affect brain function exclusively, but manifests as a whole-body disorder, the investigators propose that depression is, in part, a disorder of the microbiome-gut-brain-axis. Given that the gut microbiome is capable of driving stress and immune alterations that regulate dysfunctional brain circuitry, contributing to depressive symptomology, including cognitive dysfunction and negative biases. Therefore, the current project will be the first to assess the gut microbiome in MDD, whilst undergoing an exercise intervention in conjunction with monitoring dietary intakes. To achieve this, a RCT will be conducted with two groups of adults with MDD randomized to either a control (usual/standard care) or exercise intervention (aerobic exercise + usual/standard care). The intervention period will last 12-weeks, with those in the exercise group receiving an aerobic exercise program tailored via progressive overload to get them to meet, and then exceed the national physical activity guidelines (\>150min of moderate activity per week) by the 12-week mark. Each group will be assessed pre-, mid-, and post-intervention for depressive symptoms, cognition, negative biases, along with diet information, with mechanistic insights gained from evaluation of gut microbiome composition and function, and gut metabolites in the context of microbiota-gut-brain axis signaling. Prior to enrollment, participants will be informed about the study via a participant information leaflet, and any participant who provides written informed consent to their participation in the study, will then be screened for eligibility and enrolled if eligible.