title: Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities.
abstract: BACKGROUND
  Persistent low-grade immune-inflammatory processes, oxidative and nitrosative stress (O&amp;NS), and hypothalamic-pituitary-adrenal axis activation are integral to the pathophysiology of major depressive disorder (MDD). The microbiome, intestinal compositional changes, and resultant bacterial translocation add a new element to the bidirectional interactions of the gut-brain axis; new evidence implicates these pathways in the patho-aetiology of MDD. In addition, abnormalities in the gut-brain axis are associated with several chronic non-communicable disorders, which frequently co-occur in individuals with MDD, including but not limited to irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), obesity, and type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  We searched the PubMed/MEDLINE database up until May 1, 2016 for studies which investigated intestinal dysbiosis and bacterial translocation (the 'leaky gut') in the pathophysiology of MDD and co-occurring somatic comorbidities with an emphasis on IBS, CFS, obesity, and T2DM.
  
  
  RESULTS
  The composition of the gut microbiota is influenced by several genetic and environmental factors (e.g. diet). Several lines of evidence indicate that gut-microbiota-diet interactions play a significant pathophysiological role in MDD and related medical comorbidities. Gut dysbiosis and the leaky gut may influence several pathways implicated in the biology of MDD, including but not limited to immune activation, O&amp;NS, and neuroplasticity cascades. However, methodological inconsistencies and limitations limit comparisons across studies.
  
  
  CONCLUSIONS
  Intestinal dysbiosis and the leaky gut may constitute a key pathophysiological link between MDD and its medical comorbidities. This emerging literature opens relevant preventative and therapeutic perspectives.
authors.affiliation: McMaster Integrative Neuroscience Discovery and Study (MiNDS), McMaster University, Hamilton, Ont., Canada.
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Slyepchenko
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.forename: Felice N
authors.initials: FN
authors.lastname: Jacka
authors.forename: Cristiano A
authors.initials: CA
authors.lastname: Köhler
authors.forename: Tatiana
authors.initials: T
authors.lastname: Barichello
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: Iria
authors.initials: I
authors.lastname: Grande
authors.forename: Jane A
authors.initials: JA
authors.lastname: Foster
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.forename: André F
authors.initials: AF
authors.lastname: Carvalho
mesh_terms: D018988:Bacterial Translocation; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000150:complications* / Q000382:microbiology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000382:microbiology / Q000503:physiopathology; D004032:Diet; D015673:Fatigue Syndrome, Chronic / Q000150:complications / Q000382:microbiology / Q000503:physiopathology; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000382:microbiology / Q000503:physiopathology; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D009765:Obesity / Q000150:complications / Q000382:microbiology / Q000503:physiopathology