Finding intestinal fortitude: Integrating the microbiome into a holistic view of depression mechanisms, treatment, and resilience

• Published in: Neurobiology of disease Vol. 135; p. 104578
• Main Authors: Flux, M.C., Lowry, Christopher A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2020; Elsevier
• Subjects: Central nervous system; Central Nervous System - metabolism; Central Nervous System - microbiology; Depression; Depression - microbiology; Depression - physiopathology; Endocrine system; Gastrointestinal Microbiome - physiology; Gastrointestinal Tract - metabolism; Gastrointestinal Tract - physiopathology; Humans; Immune system; Inflammation; Mental Disorders - metabolism; Mental Disorders - microbiology; Microbiome; Microbiome-gut-brain axis; Microbiota; Microbiota - physiology; Prebiotics; Probiotics; FRL; WGS; BBB; PATHOS-D; Central nervous system; ACTH; SPF; MDD; PFC; TNF; IFNɣ; OTU; Microbiota; CA1; Spp; CA3; MAMP; PNS; LBP; STAMP; FSL; DST; MS; CMS; GAD; Cg1; IL-1β; MAPK; SCFA; IL-6; Prebiotics; Probiotics; fMRI; SSRI; CRH; GABA; HPA; 5-HT; Microbiome; IDO1; POMS; MCP-1; RCT; GALT; ANS; BDI; CNS; IBD; 3-HK; LPS; Nrf2; NMDA; SNS; TLR; Immune system; GF; ACC; DOPAC; Endocrine system; BDNF; HSCL-90; GHQ-28; Treg; Depression; HADS; MGB; Inflammation; PrL; FMT; Microbiome-gut-brain axis; PAMP; Con-A; HVA; TrkB; TrpV1; DAMP
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2019.104578

Depression affects at least 322 million people globally, or approximately 4.4% of the world's population. While the earnestness of researchers and clinicians to understand and treat depression is not waning, the number of individuals suffering from depression continues to increase over and above the rate of global population growth. There is a sincere need for a paradigm shift. Research in the past decade is beginning to take a more holistic approach to understanding depression etiology and treatment, integrating multiple body systems into whole-body conceptualizations of this mental health affliction. Evidence supports the hypothesis that the gut microbiome, or the collective trillions of microbes inhabiting the gastrointestinal tract, is an important factor determining both the risk of development of depression and persistence of depressive symptoms. This review discusses recent advances in both rodent and human research that explore bidirectional communication between the gut microbiome and the immune, endocrine, and central nervous systems implicated in the etiology and pathophysiology of depression. Through interactions with circulating inflammatory markers and hormones, afferent and efferent neural systems, and other, more niche, pathways, the gut microbiome can affect behavior to facilitate the development of depression, exacerbate current symptoms, or contribute to treatment and resilience. While the challenge of depression may be the direst mental health crisis of our age, new discoveries in the gut microbiome, when integrated into a holistic perspective, hold great promise for the future of positive mental health. [Display omitted] •The gut microbiome affects depression bidirectional communication with immune, endocrine, and central nervous systems•The gut microbiome can alter the balance of local and circulating inflammatory markers and the activity of immune cells•The gut microbiome can affect the output of the hypothalamic pituitary adrenal (HPA) axis•The gut microbiome influences the brain through altering tryptophan metabolism and producing other neuroactive molecules•Each of these three systems can affect the balance of microbiota in the gut and play a role in intestinal permeability