The Gut Microbiome and Diet in Psychiatry: Focus on Depression

Sarah Dash; Gerard Clarke; Michael Berk; Felice N. Jacka


Curr Opin Psychiatry. 2015;28(1):1-6. 

In This Article

Leaky Gut

Beyond metabolism, microbial balance influences the protective epithelial gut barrier. The integrity of the mucosal gut barrier is maintained by tight junctions that control the flow of molecules between the gastrointestinal tract and bloodstream.[64] Compromised integrity of the epithelial barrier has been termed 'leaky gut' and this condition has been associated with a wide range of intestinal and systemic diseases, including allergies, autoimmune disorders, asthma, IBD and, speculatively, to mental health,[65,66] although it is important to note that most data are correlational at this stage.[67]

One consequence of intestinal permeability, or leaky gut, is the increase in circulating bacteria-derived lipopolysaccharide (LPS), which triggers both an immunological and inflammatory response characterized by increased systemic pro-inflammatory cytokines.[68] Inflammation is suggested as a causative factor in depression[69] and it is notable that elevated serum levels of IgM and IgA against Gram-negative enterobacteria-derived LPS are elevated in chronic depression.[70] Moreover, bacterial translocation across the gut wall induces an autoimmune response to serotonin that is associated with fatigue and illness behaviour.[71] A novel animal model of depression has been developed on the basis of this model whereby chronic LPS administration induces the behavioural phenotype of depression and is reversed by antidepressants.[72] Relevant to this review, intestinal permeability is promoted by high-fat diets.[73]