From: login23x@gmail.com   
      
   Mol Psychiatry. 2016 Jun; 21(6): 738–748.   
   Published online 2016 Apr 19. doi:  10.1038/mp.2016.50   
   PMCID: PMC4879184   
      
      
   From gut dysbiosis to altered brain function and mental illness: mechanisms   
   and pathways   
      
      
   G B Rogers,1,* D J Keating,2 R L Young,3 M-L Wong,4 J Licinio,4 and S   
   Wesselingh1   
   Author information ► Article notes ► Copyright and License information ►   
   This article has been cited by other articles in PMC.   
   Go to:   
   Abstract   
   The human body hosts an enormous abundance and diversity of microbes, which   
   perform a range of essential and beneficial functions. Our appreciation of the   
   importance of these microbial communities to many aspects of human physiology   
   has grown    
   dramatically in recent years. We know, for example, that animals raised in a   
   germ-free environment exhibit substantially altered immune and metabolic   
   function, while the disruption of commensal microbiota in humans is associated   
   with the development of a    
   growing number of diseases. Evidence is now emerging that, through   
   interactions with the gut–brain axis, the bidirectional communication system   
   between the central nervous system and the gastrointestinal tract, the gut   
   microbiome can also influence    
   neural development, cognition and behaviour, with recent evidence that changes   
   in behaviour alter gut microbiota composition, while modifications of the   
   microbiome can induce depressive-like behaviours. Although an association   
   between enteropathy and    
   certain psychiatric conditions has long been recognized, it now appears that   
   gut microbes represent direct mediators of psychopathology. Here, we examine   
   roles of gut microbiome in shaping brain development and neurological   
   function, and the mechanisms    
   by which it can contribute to mental illness. Further, we discuss how the   
   insight provided by this new and exciting field of research can inform care   
   and provide a basis for the design of novel, microbiota-targeted, therapies.   
      
   Go to:   
   Introduction   
   The disruption of the microbes that are resident in our gastrointestinal tract   
   has long been implicated in the development or exacerbation of mental   
   disorders. There is, for example, a long history of anecdotal reports of   
   psychiatric side-effects of    
   antibiotics, even in those without a premorbid psychiatric history.1 There   
   have also been attempts to influence the composition of the gut microbiota to   
   achieve clinical benefit. For example, in the first decades of the twentieth   
   century, probiotic    
   preparations containing Lactobacillus strains were marketed widely as a means   
   to improve mental health or treat psychiatric disorders.2 These approaches   
   fell from favour in the 1920s because of a lack of mechanistic understanding   
   and their link to the    
   increasingly unfashionable ‘autointoxication' model. However, the interest   
   in the role of gut microbes in mental health, and our ability to improve   
   psychiatric wellbeing through their manipulation, is resurgent.2, 3   
      
   In this review, we consider the potential of dysbiosis to contribute to   
   psychopathology and the evidence linking disruption of gut microbiota with   
   specific psychiatric disorders. We examine the role of the microbiome in   
   neurological development and    
   regulation, and consider its contribution to aging-related morbidity. Finally,   
   we discuss the potential for modification of the gut microbiome to provide   
   clinical benefit in the context of altered brain function.   
      
   Go to:   
   Regulation of neurological function by the gut microbiome   
   The potential contribution of bidirectional communication between the gut and   
   central nervous system (CNS) is suggested by high rates of comorbidity between   
   gastrointestinal and psychiatric illnesses.4, 5 For example, mood disorders   
   affect more than half    
   of all patients with irritable bowel syndrome,6 with antidepressants being one   
   of the most common pharmaceutical interventions for irritable bowel syndrome.4   
   The gut–brain axis consists of a bidirectional communication network that   
   monitors and    
   integrates gut functions and link them to cognitive and emotional centres of   
   the brain. It encompasses the central, autonomic and enteric nervous systems,   
   as well as the neuroendocrine, enteroendocrine and neuroimmune systems.7, 8 It   
   mediates the effects    
   of both genetic and environmental factors on brain development and function,   
   and has been implicated in the aetiology of a number of psychiatric   
   disorders.9, 10, 11, 12   
      
   In recent years, we have increasingly understood the contribution made by the   
   gut microbiome not only in the regulation of host physiology, particularly   
   metabolism and immunity,13, 14, 15, 16, 17 but also the CNS and brain   
   function.11, 18, 19 Given    
   mounting evidence that the microbiome has a key role in influencing the   
   development and function of the nervous system through its interaction with   
   the gut–brain axis, it has been suggested that a ‘microbiome–gut–brain   
   axis' may be a more    
   appropriate model.19, 20, 21, 22   
      
   The delicate balance between the human microbiome and the development of   
   psychopathologies is particularly interesting given the ease with which the   
   microbiome can be altered by external factors, such as diet,23 exposure to   
   antimicrobials24, 25 or    
   disrupted sleep patterns.26 For example, a link between antibiotic exposure   
   and altered brain function is well evidenced by the psychiatric side-effects   
   of antibiotics, which range from anxiety and panic to major depression,   
   psychosis and delirium.1 A    
   recent large population study reported that treatment with a single antibiotic   
   course was associated with an increased risk for depression and anxiety,   
   rising with multiple exposures.27 Bercik et al.28 showed that oral   
   administration of non-absorbable    
   antimicrobials transiently altered the composition of the gut microbiota in   
   adult mice and increased exploratory behaviour and hippocampal expression of   
   brain-derived neurotrophic factor (BDNF), while intraperitoneal administration   
   had no effect on    
   behaviour. Alteration of brain function may therefore add to the many reasons   
   that inappropriate antibiotic use should be avoided. It should be noted though   
   that unchecked bacterial infection also represents an acute stressor, and has   
   been shown to be    
   associated with memory dysfunction in mice.29   
      
      
   [continued in next message]   
      
   --- SoupGate-Win32 v1.05   
    * Origin: you cannot sedate... all the things you hate (1:229/2)