Microbiota and Mental Health
Bested et al. provide an intriguing overview of the long history of investigation into the 'gut–brain' axis, including the first suggestions in the 1800s that systemic disease, including mental health disorders, could be rooted in intestinal 'self-infective' processes and that increasing rates of melancholia may be a by-product of urban and western civilization, possibly mediated by dietary habits and toxins arising from the gastrointestinal tract.
The evidence that the gut microbiota influences brain and behaviour is now rapidly expanding and is a view that has started to gain traction in the literature.[14,32,33] This is largely due to compelling preclinical evidence that the gut microbiota can influence behaviours of relevance to anxiety[34,35,36,37] and that manipulation of the gut microbiota with specific probiotics[38,39] or with antibiotics[40,41] can influence depression-like behaviours. The microbiota likely recruits the gut–brain axis to exert effects at the level of the central nervous system (CNS). This is a reciprocal relationship, with the CNS moderating, for example, gut motility and secretion. Both humoral and neural mechanisms are plausible, with the role of the vagus nerve in particular receiving much attention.
Independent studies have now confirmed that an anxious phenotype can be transferred via the gut microbiota.[44,45] Moreover, it appears that both prenatal and early-life stress, both risk factors for psychopathology, engender potentially deleterious gut microbiota alterations that can manifest during critical neurodevelopmental periods and that may persist into adulthood. For example, Bailey et al. monitored gut bacteria colonization in infant monkeys whose mothers were either undisturbed or stressed during pregnancy, finding marked changes in microflora concentrations in the offspring of stressed mothers. Certainly, the animal data suggest that early colonization of gut microbiota influences the programming of the stress response system in offspring. Moreover, preclinical studies have shown that both early life stress and surgically induced depression produce alterations in the gut microbiota.[48,49] Adverse early life exposures are related to the stress response and the risk for mental disorders in offspring; thus, the understanding that prenatal and early life stress modulates the microbial composition of the gut in infants suggests implications for the vulnerability to mental disorders in children. It is worth noting that the adult gut microbiome appears to be resilient and begins recovery immediately after disruption, although the impact of very early life or repeated antibiotic use on the microbiome can be pervasive and long-lasting.
Given the ability of the gut microbiota to influence serotonin and its precursor, tryptophan, regulate the stress response[54,55] and modulate cognition[56,57] and behaviour,[58,59] the potential importance of the gut microbiota to psychiatry in general and to depression specifically is apparent. Microbiome alterations are evident in irritable bowel syndrome (IBS), a functional gastrointestinal disorder with significant psychiatric comorbidity. However, only one preliminary study has specifically examined microbiome alterations in depression and, although some correlations were established, the overall species richness and diversity was not different to healthy controls. More detailed studies are now warranted to interrogate this intriguing proposition. Recent indications that certain probiotic formulations can both produce beneficial psychological effects in healthy populations and modulate brain activity in an imaging study underline the importance of such a venture.
Curr Opin Psychiatry. 2015;28(1):1-6. © 2015 Lippincott Williams & Wilkins