Review Article

The clinical outcomes of gut-brain axis (GBA) microbiota influence on psychiatric disordersThe clinical outcomes of gut-brain axis (GBA) microbiota influence on psychiatric disorders


The gut microbiome plays an important role in the health of the body. The study of its effect on mental problems has become the main topic of this study. As a matter of fact, every change in the gut microbiota composition can influence on mood and anxiety and vice versa. So, considering this “microbiota-gut-brain” axis (GBA) is so important. In this narrative review, the most recent reproduced information on GBA roles in neuropsychiatric disorders, and clinical significance have been considered. The gut microbial population is formed from birth and transforms from an immature state to the postnatal period into a more intricate and diverse adult ecosystem. In this review, we had some findings that GBA implicated in some psychiatric problems which can be a dysregulation consequence. In addition, some bacteria have been implicated in causing mental disorders in humans such as depression, obsessive-compulsive disorder, psychiatric disorders, stress disorders, schizophrenia and, autism. The absence of balance in GBA natural state can cause several negative consequences on host health which leads to neurological problems. Possibly, findings were delineating an interesting new etiological pathway for future exploration.

1. Haghighat N, Rajabi S, Mohammadshahi M. Effect of synbiotic and probiotic supplementation on serum brain-derived neurotrophic factor level, depression and anxiety symptoms in hemodialysis patients: a randomized, double-blinded, clinical trial. Nutr Neurosci 2021; 24: 490-499.
2. Frank MG, Fonken LK, Dolzani SD, Annis JL, Siebler PH, Schmidt D, et al. Immunization with Mycobacterium vaccae induces an anti-inflammatory milieu in the CNS: Attenuation of stress-induced microglial priming, alarmins and anxiety-like behavior. Brain Behav Immun 2018; 73: 352-363.
3. Sommers-Spijkerman MPJ, Trompetter HR, Schreurs KMG, Bohlmeijer ET. Compassion-focused therapy as guided self-help for enhancing public mental health: A randomized controlled trial. J Consult Clin Psychol 2018; 86: 101-115.
4. Bermúdez-Humarán LG, Salinas E, Ortiz GG, Ramirez-Jirano LJ, Morales JA, Bitzer-Quintero OK. From probiotics to psychobiotics: live beneficial bacteria which act on the brain-gut axis. Nutrients 2019; 11: 890.
5. Gomaa EZ. Human gut microbiota/microbiome in health and diseases: a review. Antonie Van Leeuwenhoek 2020; 113: 2019-2040.
6. O’Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep 2006; 7: 688-693.
7. Ursell LK, Haiser HJ, Treuren WV, Garg N, Reddivari L, Vanamala J, et al. The intestinal metabolome: an intersection between microbiota and host. Gastroenterology 2014; 146: 1470-1476.
8. Carabotti M, Scirocco A, Antonietta Maselli M, Severia C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol 2015; 28: 203-209.
9. Martin CR, OsadchiyV, Kalani A, Mayer EA. The brain-gut-microbiome axis. Cell Mol Gastroenterol Hepatol 2018; 6: 133-148.
10. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 2011; 108: 16050-16055.
11. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 2012; 61: 364-371.
12. Singh V, Roth S, Llovera G, Sadler R, Garzetti D, Stecher B, et al. Microbiota dysbiosis controls the neuroinflammatory response after stroke. J Neurosci 2016; 36: 7428-7440.
13. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 2015; 161: 264-276.
14. Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A 2009; 106: 3698-3703.
15. Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A 2008; 105: 16767-16772.
16. Haghikia A, Jorg S, Duscha A, Berg J, Manzel A, Waschbisch A, et al. Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity 2015; 43: 817-829.
17. Goehler LE, Gaykema RPA, Opitz N, Reddaway R, Badr N, Lyte M. Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni. Brain Behav Immun 2005; 19: 334-344.
18. Barrett E, Ross RP, O'Toole PW, Fitzgerald GF, Stanton C. γ- Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 2012; 113: 411-417.
19. Minuk GY. Gamma-aminobutyric-acid (GABA) production by eight common bacterial pathogens. Scand J Infect Dis 1986; 18: 465-467.
20. Chan L, Wei Y, Hashimoto K. Brain–gut–microbiota axis in depression: A historical overview and future directions. Brain Res Bulletin 2022;182:44-56.
21. Asano Y, Hiramoto T, Nishino R, Aiba Y, Kimura T, Yoshihara K, et al. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Physiol Gastrointest Liver Physiol 2012; 303: G1288-1295.
22. Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG. Minireview: gut microbiota: the neglected endocrine organ. Mol Endocrinol 2014; 28: 1221-1238.
23. Ríos-Covián D, Ruas-Madiedo P, Margolles A, Gueimonde M, de Los Reyes-Gavilán CG, Salazar N. Intestinal short chain fatty acids and their link with diet and human health. Front Microbiol 2016; 7: 185.
24. Byrne CS, Chambers ES, Alhabeeb H, Chhina N, Morrison DJ, Preston T, et al. Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods. Am J Clin Nutr 2016; 104: 5-14.
25. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol 2016; 16: 341-352.
26. Lucas S-M, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br J Pharmacol 2006; 147 Suppl 1(Suppl 1): S232-240.
27. Buie T, Campbell DB, Fuchs GJ 3rd, Furuta GT, Levy J, Vandewater J, et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 2010; 125 Suppl 1: S1-18.
28. Krajmalnik-Brown R, Lozupone C, Kang D-W, Adams JB. Gut bacteria in children with autism spectrum disorders: challenges and promise of studying how a complex community influences a complex disease. Microb Ecol Health Dis 2015; 26: 26914.
29. Mulle JG, Sharp WG, Cubells JF. The gut microbiome: a new frontier in autism research. Curr Psychiatry Rep 2013; 15: 337.
30. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol 2005; 54: 987-991.
31. Tomova A, Husarova V, Lakatosova S, Bakos J, Vlkova B, Babinska K, et al. Gastrointestinal microbiota in children with autism in Slovakia. Physiol Behav 2015; 138: 179-187.
32. Luna RA, Savidge TC, Williams KC. The brain-gut-microbiome axis: What role does it play in autism spectrum disorder? Curr Dev Disord Rep 2016; 3: 75-81.
33. Turna J, Grosman Kaplan K, Anglin R, Van Ameringen M. “What’s Bugging the gut in OCD?” A review of the gut microbiome in obsessive–compulsive disorder. Depress Anxiety 2016; 33: 171-178.
34. Rees JC. Obsessive-compulsive disorder and gut microbiota dysregulation. Med Hypotheses 2014; 82: 163-166.
35. Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013; 155: 1451-1463.
36. Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: How gut microbes shape human behavior. J Psychiatr Res 2015; 63: 1-9.
37. Goehler LE, Park SM, Opitz N, Lyte M, Gaykema RP. Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior. Brain Behav Immun 2008; 22: 354-366.
38. Gareau MG, Wine E, Rodrigues DM, Cho JH, Whary MT, Philpott DJ, et al. Bacterial infection causes stress-induced memory dysfunction in mice. Gut 2011; 60: 307-317.
39. Julio-Pieper M, Bravo JA, Aliaga E, Gotteland M. Review article: intestinal barrier dysfunction and central nervous system disorders – a controversial association. Aliment Pharmacol Ther 2014; 40: 1187-1201.
40. Lomax AE, Pradhananga S, Sessenwein JL, O’Malley D. Bacterial modulation of visceral sensation: mediators and mechanisms. Am J Physiol Gastrointest Liver Physiol 2019: 317: G363-G372.
41. Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry 2013; 74: 720-726.
42. Clarke G, Cryan JF, Dinan TG, Quigley EM. Review article: probiotics for the treatment of irritable bowel syn-drome–focus on lactic acid bacteria. Aliment Pharmacol Ther 2012; 35: 403-413.
43. Menees SB, Maneerattannaporn M, Kim HM, Chey WD. The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis. Am J Gastroenterol 2012; 107: 28-35; quiz 36.
44. Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, et al. Minocycline as adjunctive therapy forpatients with unipolar psychoticdepression: an open-label study. Prog Neuropsychopharmacol Biol Psychiatry 2012; 37: 222-226.
45. Borre Y, Sir V, de Kivit S, Westphal KG, Olivier B, Oosting RS. Minocycline restores spatial but not fear memory in olfactory bulbectomized rats. Eur J Pharmacol 2012; 697: 59-64.
IssueVol 15 No 1 (2023) QRcode
SectionReview Article(s)
Gut-brain axis (GBA); Microbiota; Obsessive-compulsive disorder; Psychiatric disorders; Stress-related disorders; Schizophrenia; Autism

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Navidinia M, Goudarzi M, Seyfi E. The clinical outcomes of gut-brain axis (GBA) microbiota influence on psychiatric disordersThe clinical outcomes of gut-brain axis (GBA) microbiota influence on psychiatric disorders. Iran J Microbiol. 2023;15(1):1-9.