Abstract
Purpose of Review
The human gut microbiome is involved in a bi-directional communication pathway with the central nervous system (CNS), termed the microbiota–gut–brain axis. The microbiota–gut–brain axis is believed to mediate or modulate various central processes through the vagus nerve. The microbiota–gut–brain axis is involved with the production of microbial metabolites and immune mediators which trigger changes in neurotransmission, neuroinflammation, and behavior. Little is understood about the utilization of microbiome manipulation to treat disease.
Recent Findings
Though studies exploring the role of the microbiome in various disease processes have shown promise, mechanisms remain unclear and evidence-based treatments for most illnesses have not yet been developed. The animal studies reviewed in the present investigation include an array of basic science studies that clarify mechanisms by which the microbiome may affect mental health. More evidence is needed, particularly as it relates to translating this work to humans.
Summary
The studies presented in this review demonstrate encouraging results in the treatment of depression. Limitations include small sample sizes and heterogeneous methodology. The exact mechanism by which the gut microbiota causes or alters neuropsychiatric disease states is not fully understood. In this review, we focus on recent studies investigating the relationship between gut microbiome dysbiosis and the pathogenesis of depression.
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Change history
27 March 2023
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s11916-023-01106-5
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
• Frank DN, Pace NR. Gastrointestinal microbiology enters the metagenomics era. Curr Opin Gastroenterol. 2008;24(1):4–10 This is a great overall review of gastrointestinal microbiology.
• Sherwin E, Sandhu KV, Dinan TG, Cryan JF. May the force be with you: the light and dark sides of the microbiota–gut–brain axis in neuropsychiatry. CNS Drugs. 2016;30(11):1019–41 This is a great overall review of gastrointestinal microbiota and neuropsychiatry.
• Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015;9:392 This is an excellent manuscript on the gut microbiome and psychiatric disorders.
•• Sampson TR, Mazmanian SK. Control of brain development, function, and behavior by the microbiome. Cell Host Microbe. 2015;17(5):565–76 This is a great review of gastrointestinal microbiome and brain development and function.
Forsythe P, Kunze WA. Voices from within: gut microbes and the CNS. Cell Mol Life Sci. 2013;70(1):55–69.
Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism – comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011;11(1):22.
Li C, Cui L, Yang Y, Miao J, Zhao X, Zhang J, et al. Gut microbiota differs between Parkinson’s disease patients and healthy controls in Northeast China. Front Mol Neurosci. 2019;12:171.
Aizawa E, Tsuji H, Asahara T, Takahashi T, Teraishi T, Yoshida S, et al. Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. J Affect Disord. 2016;202:254–7.
Xu R, Wu B, Liang J, He F, Gu W, Li K, Luo Y, Chen J, Gao Y, Wu Z, Wang Y, Zhou W, Wang M. Altered gut microbiota and mucosal immunity in patients with schizophrenia. Brain Behav Immun. 2020;85:120–7. https://doi.org/10.1016/j.bbi.2019.06.039.
•• Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJL, et al. Burden of depressive disorders by country, sex, age, and year: findings from the Global Burden of Disease Study 2010. Hay PJ, editor. PLoS Med. 2013;10(11):e1001547 This is a great review of epidemiology of depressive disorders.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders [Internet]. 5th Editio. American Psychiatric Association; 2013.
Bose J, Hedden SL, Lipari RN, Park-Lee E. Key substance use and mental health indicators in the United States: results from the 2017 National Survey on Drug Use and Health 2017.
Greenberg PE, Fournier A-A, Sisitsky T, Pike CT, Kessler RC. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). J Clin Psychiatry. 2015;76(02):155–62.
• Jakobsson HE, Jernberg C, Andersson AF, Sjölund-Karlsson M, Jansson JK, Engstrand L. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. Ratner AJ, editor. PLoS One. 2010;5(3):e9836 This is a great review of short- and long-term differing effects of human throat and gut biome.
Jernberg C, Löfmark S, Edlund C, Jansson JK. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 2007;1(1):56–66.
Adamsson I, Nord CE, Lundquist P, Sjöstedt S, Edlund C. Comparative effects of omeprazole, amoxycillin plus metronidazole versus omeprazole, clarithromycin plus metronidazole on the oral, gastric and intestinal microflora in Helicobacter pylori-infected patients. J Antimicrob Chemother. 1999;44(5):629–40.
Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. Eisen JA, editor. PLoS Biol. 2008;6(11):e280.
Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1(6):6ra14.
Bisanz JE, Upadhyay V, Turnbaugh JA, Ly K, Turnbaugh PJ. Meta-analysis reveals reproducible gut microbiome alterations in response to a high-fat diet. Cell Host Microbe. 2019;26(2):265–272.e4.
Ju M, Liu Y, Li M, Cheng M, Zhang Y, Deng G, et al. Baicalin improves intestinal microecology and abnormal metabolism induced by high-fat diet. Eur J Pharmacol. 2019;857:172457.
• Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005;102(31):11070–5 This is a great review on obesity and gut biome.
Rodríguez JM, Murphy K, Stanton C, Ross RP, Kober OI, Juge N, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Heal Dis. 2015;26(0):26050.
Cong X, Xu W, Romisher R, Poveda S, Forte S, Starkweather A, et al. Gut microbiome and infant health: brain-gut-microbiota axis and host genetic factors. Yale J Biol Med. 2016;89(3):299–308.
Werbner M, Barsheshet Y, Werbner N, Zigdon M, Averbuch I, Ziv O, Brant B, Elliott E, Gelberg S, Titelbaum M, Koren O, Avni O. Social-stress-responsive microbiota induces stimulation of self-reactive effector T helper cells. mSystems. 2019;4(4):e00292-18. https://doi.org/10.1128/mSystems.00292-18.
Tsiaoussis J, Antoniou MN, Koliarakis I, Mesnage R, Vardavas CI, Izotov BN, et al. Effects of single and combined toxic exposures on the gut microbiome: current knowledge and future directions. Toxicol Lett. 2019;312:72–97.
Kelly JR, Borre Y, O’Brien C, Patterson E, El Aidy S, Deane J, et al. Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res. 2016;82:109–18.
Hoban AE, Moloney RD, Golubeva AV, McVey Neufeld KA, O’Sullivan O, Patterson E, et al. Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat. Neuroscience. 2016;339:463–77.
Provensi G, Schmidt SD, Boehme M, Bastiaanssen TFS, Rani B, Costa A, et al. Preventing adolescent stress-induced cognitive and microbiome changes by diet. Proc Natl Acad Sci U S A. 2019;116(19):9644–51.
Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186–94.
Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012;13(9):R79.
Desbonnet L, Clarke G, Traplin A, O’Sullivan O, Crispie F, Moloney RD, et al. Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour. Brain Behav Immun. 2015;48:165–73.
Burke HM, Davis MC, Otte C, Mohr DC. Depression and cortisol responses to psychological stress: a meta-analysis. Psychoneuroendocrinology. 2005;30(9):846–56.
Morrison JH, Baxter MG. The ageing cortical synapse: hallmarks and implications for cognitive decline. Nat Rev Neurosci. 2012;13(4):240–50.
Yang Y, Cui Y, Sang K, Dong Y, Ni Z, Ma S, et al. Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature. 2018;554(7692):317–22.
Erny D, Hrabě de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18(7):965–77.
Réus GZ, Fries GR, Stertz L, Badawy M, Passos IC, Barichello T, et al. The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders. Neuroscience. 2015;300:141–54.
Black CN, Bot M, Scheffer PG, Cuijpers P, Penninx BWJH. Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology. 2015;51:164–75.
Fan W, Huo G, Li X, Yang L, Duan C. Impact of diet in shaping gut microbiota revealed by a comparative study in infants during the first six months of life. J Microbiol Biotechnol. 2014;24(2):133–43.
Skonieczna-Żydecka K, Grochans E, Maciejewska D, Szkup M, Schneider-Matyka D, Jurczak A, Łoniewsk I, Kaczmarczyk M, Marlicz W, Czerwińska-Rogowska M, Pełka-Wysiecka J, Dec K, Stachowska. Faecal short chain fatty acids profile is changed in polish depressive women. Nutrients. 2018;10(12):1939. https://doi.org/10.3390/nu10121939.
Jesulola E, Micalos P, Baguley IJ. Understanding the pathophysiology of depression: from monoamines to the neurogenesis hypothesis model - are we there yet? Behav Brain Res. 2018;341:79–90 Elsevier B.V.
Kazemi A, Noorbala AA, Azam K, Eskandari MH, Djafarian K. Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: a randomized clinical trial. Clin Nutr. 2019;38(2):522–8.
Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015;48:258–64.
Kiecolt-Glaser JK, Wilson SJ, Bailey ML, Andridge R, Peng J, Jaremka LM, et al. Marital distress, depression, and a leaky gut: translocation of bacterial endotoxin as a pathway to inflammation. Psychoneuroendocrinology. 2018;98:52–60.
Rudzki L, Ostrowska L, Pawlak D, Małus A, Pawlak K, Waszkiewicz N, et al. Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: a double-blind, randomized, placebo controlled study. Psychoneuroendocrinology. 2019;100:213–22.
Lew LC, Hor YY, Yusoff NAA, Choi SB, Yusoff MSB, Roslan NS, et al. Probiotic Lactobacillus plantarum P8 alleviated stress and anxiety while enhancing memory and cognition in stressed adults: a randomised, double-blind, placebo-controlled study. Clin Nutr. 2019;38(5):2053–64.
Slykerman RF, Hood F, Wickens K, Thompson JMD, Barthow C, Murphy R, et al. Effect of Lactobacillus rhamnosus HN001 in pregnancy on postpartum symptoms of depression and anxiety: a randomised double-blind placebo-controlled trial. EBioMedicine. 2017;24:159–65.
Akkasheh G, Kashani-Poor Z, Tajabadi-Ebrahimi M, Jafari P, Akbari H, Taghizadeh M, et al. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial. Nutrition. 2016;32(3):315–20.
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Alexander Capuco, Ivan Urits, Jamal Hasoon, Rebecca Chun, Brittany Gerald, Jason K Wang, Anh L. Ngo, Thomas Simopoulos, Matthew M. Colontonio, Tomasina Q. Parker-Actlis, Mitchell C. Fuller, and Omar Viswanath declare no conflict of interest. Alan Kaye is a Section Editor for Current Pain and Headache Reports. He has not been involved in the editorial handling of this manuscript. Dr. Kaye is also a speaker for Merck.
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Capuco, A., Urits, I., Hasoon, J. et al. RETRACTED ARTICLE: Gut Microbiome Dysbiosis and Depression: a Comprehensive Review. Curr Pain Headache Rep 24, 36 (2020). https://doi.org/10.1007/s11916-020-00871-x
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DOI: https://doi.org/10.1007/s11916-020-00871-x