From gut to brain: unveiling probiotic effects through a neuroimaging perspective-A systematic review of randomized controlled trials

The gut-brain axis, a bidirectional communication network between the gastrointestinal system and the brain, significantly influences mental health and behavior. Probiotics, live microorganisms conferring health benefits, have garnered attention for their potential to modulate this axis. However, their effects on brain function through gut microbiota modulation remain controversial. This systematic review examines the effects of probiotics on brain activity and functioning, focusing on randomized controlled trials using both resting-state and task-based functional magnetic resonance imaging (fMRI) methodologies. Studies investigating probiotic effects on brain activity in healthy individuals and clinical populations (i.e., major depressive disorder and irritable bowel syndrome) were identified. In healthy individuals, task-based fMRI studies indicated that probiotics modulate brain activity related to emotional regulation and cognitive processing, particularly in high-order areas such as the amygdala, precuneus, and orbitofrontal cortex. Resting-state fMRI studies revealed changes in connectivity patterns, such as increased activation in the Salience Network and reduced activity in the Default Mode Network. In clinical populations, task-based fMRI studies showed that probiotics could normalize brain function in patients with major depressive disorder and irritable bowel syndrome. Resting-state fMRI studies further suggested improved connectivity in mood-regulating networks, specifically in the subcallosal cortex, amygdala and hippocampus. Despite promising findings, methodological variability and limited sample sizes emphasize the need for rigorous, longitudinal research to clarify the beneficial effects of probiotics on the gut-brain axis and mental health.