Neuroinflammatory remodeling of the anterior cingulate cortex as a key driver of mood disorders in gastrointestinal disease and disorders

•Clinical literature reveals GIDD are associated with reduced cortical thickness, hyperactivity, and altered functional connectivity of the ACC.•Preclinical studies reveal gut inflammation drives neuroinflammation, and remodelling of neuronal structures including the ACC.•The ACC network provides a context (schema) in which to interpret internal (e.g. pain) and external (e.g. threats) stimuli.•We propose chronic gut dysfunction drives neural remodeling that biases the ACC network towards a negative schema, driving physiological responses towards non-existent or anticipated threats.•This negative schema promotes an imbalance between parasympathetic and sympathetic nervous system responses, in turn perpetuating and exacerbating gut dysfunction.