Microbiota-Gut-Brain Axis and Mental Health
DOI:
https://doi.org/10.14738/bjhmr.106.16010Keywords:
Anxiety, Depression, Intestinal Microbiom, Scoping review, Mental HealthAbstract
Intestinal microbes seem to be direct mediators in psychopathology, although the exact relationship between microbiome/microbiota and psychism is unknown. This brief structured bibliographic review is quick secondary research conducted with the aim of synthetically compiling the clinically relevant information on this topic, taking into account that the qualified primary research published is limited, complex and heterogeneous. Non systematic search in several well qualified international academic bibliographic indexes obtaining n=80 references. Results revealed that host microbiota have multiple psycho-neuro-gastro-enterological implications via neuroendocrine, nervous and immune pathways. Microbiota also entail an essential impact on hippocampus-dependent learning and memory. Next, the relevant integration of genomics and metabolomics is highlighted so as to explain its possible causal effects on anxiety, depressive and other disorders, as well as the bidirectional implication of the entire vagus nerve in depression through the microbiota-gut-brain axis. Lastly, the possible favourable effects of interventions on such axis in order to improve mental health are mentioned. On the other hand, psychotropic drugs are increasingly used to treat functional gastrointestinal disorders. In conclusions, to modulate intestinal microbiota is a promising and useful therapeutic strategy for various mental, behavioural and neurodevelopmental disorders. It is important to coordinate relevant complementary medical care specialisations in this regard.
References
Hashimoto K. Emerging role of the host microbiome in neuropsychiatric disorders: Overview and future directions. Mol Psychiatry. 2023. doi: 10.1038/s41380-023-02287-6
Shoubridge AP, Choo JM, Martin AM, Keating DJ, Wong ML, Licinio J, et al. The gut microbiome and mental health: Advances in research and emerging priorities. Mol Psychiatry. 2022; 27(4):1908–19. doi: 10.1038/s41380-022-01479-w
Shobeiri P, Kalantari A, Teixeira AL, Rezaei N. Shedding light on biological sex differences and microbiotagut-brain axis: A comprehensive review of its roles in neuropsychiatric disorders. Biol Sex Differ. 2022; 13(1):12. doi: 10.1186/s13293-022-00422-6
Gómez-Eguílaz M, Ramón-Trapero JL, Pérez-Martínez L, Blanco JR. El eje microbiota-intestino-cerebro y sus grandes proyecciones. [The microbiota-gut-brain axis and its major projections.] Rev Neurol. 2019; 68 (3):111–7. doi: 10.33588/rn.6803.2018223
Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, Soleimanpour S. A comprehensive review on the role of the gut microbiome in human neurological disorders. Clin Microbiol Rev. 2022; 35(1): e0033820. doi: 10.1128/CMR.00338-20
Hamel C, Michaud A, Thuku M, Skidmore B, Stevens A, Nussbaumer-Streit B, et al. Defining rapid reviews: A systematic scoping review and thematic analysis of definitions and defining characteristics of rapid reviews. J Clin Epidemiol. 2021; 129:74–85. doi: 10.1016/j.jclinepi.2020.09.041
Bastiaanssen TFS, Cryan JF. The microbiota-gut-brain axis in mental health and medication response: Parsing directionality and causality. Int J Neuropsychopharmacol. 2021; 24(3):216–20. doi: 10.1093/ijnp/pyaa088
Del-Campo-Moreno R, Alarcón-Cavero T, D'Auria G, Delgado-Palacio S, Ferrer-Martínez M. Microbiota and human health: Characterization techniques and transference. Enferm Infecc Microbiol Clin (engl ed). 2018; 36(4):241–5. doi: 10.1016/j.eimc.2017.02.007
Cooke MB, Catchlove S, Tooley KL. Examining the influence of the human gut microbiota on cognition and stress: A systematic review of the literature. Nutrients. 2022; 14(21):4623. doi: 10.3390/nu14214623
Zhu P, Lu T, Wu J, Fan D, Liu B, Zhu X, et al. Gut microbiota drives macrophage-dependent self-renewal of intestinal stem cells via niche enteric serotonergic neurons. Cell Res. 2022; 32(6):555–69. doi: 10.1038/s41422-022-00645-7 Erratum in: Cell Res. 2022; 32(12):1132. doi: 10.1038/s41422-022-00734-7
Aderbal S, Ana M, Filho S, Selma S, Bandeira TL, Bandeira IM, et al. The brain-gut-microbiome axis. Int J Psychiatr Res. 2022; 5(5):1–9. https://www.scivisionpub.com/pdfs/the-braingutmicrobiome-axis-2494.pdf
Duffy M, Boggiano VL, Ganesh R, Mueller M. Functional gastrointestinal disorders. Prim Care. 2023; 50(3):429–46. doi: 10.1016/j.pop.2023.03.006
Ungaro F, Massimino L, Furfaro F, Rimoldi V, Peyrin-Biroulet L, D'Alessio S, Danese S. Metagenomic analysis of intestinal mucosa revealed a specific eukaryotic gut virome signature in early-diagnosed inflammatory bowel disease. Gut Microbes. 2019; 10(2):149–58. doi: 10.1080/19490976.2018.1511664
Sterling KG, Dodd GK, Alhamdi S, Asimenios PG, Dagda RK, De-Meirleir KL, et al. Mucosal immunity and the gut-microbiota-brain-axis in neuroimmune disease. Int J Mol Sci. 2022; 23(21):13328. doi: 10.3390/ijms232113328
Gershon MD. The second brain. A groundbreaking new understanding of nervous disorders of the stomach and intestine. New York, US: HarperCollins Publishers; 1999.
National Institute of Diabetes and Digestive and Kidney Diseases. Irritable bowel syndrome (IBS). 2017. https://www.niddk.nih.gov/health-information/digestive-diseases/irritable-bowel-syndrome/definitionfacts.
Sebastián-Domingo JJ. Síndrome del intestino irritable. [Irritable bowel syndrome.] Med Clin (Barc). 2022; 158(2):76–81. doi: 10.1016/j.medcli.2021.04.029
Lacy BE, Patel NK. Rome criteria and a diagnostic approach to irritable bowel syndrome. J Clin Med. 2017; 6(11):99. doi: 10.3390/jcm6110099
Mearin F, Ciriza C, Mínguez M, Rey E, Mascort JJ, Peña E, et al. Guía de práctica clínica del síndrome del intestino irritable con estreñimiento y estreñimiento funcional en adultos: concepto, diagnóstico y continuidad asistencial. (Parte 1 de 2). [Clinical practice guidelines. Irritable bowel syndrome with constipation and functional constipation in adults: Concept, diagnosis, and healthcare continuity. (Part 1 of 2).] Semergen. 2017; 43(1):43–56. doi: 10.1016/j.semerg.2016.06.009
Mearin F, Ciriza C, Mínguez M, Rey E, Mascort JJ, Peña E, et al. Guía de práctica clínica del síndrome del intestino irritable con estreñimiento y estreñimiento funcional en adultos: tratamiento. (Parte 2 de 2). [Irritable bowel syndrome with constipation and functional constipation in adults: Treatment (Part 2 of 2).] Aten Primaria. 2017; 49(3):177–94. doi: 10.1016/j.aprim.2017.01.003
Canakis A, Haroon M, Weber HC. Irritable bowel syndrome and gut microbiota. Curr Opin Endocrinol Diabetes Obes. 2020; 27(1):28–35. doi: 10.1097/MED.0000000000000523
Kuijer EJ, Steenbergen L. The microbiota-gut-brain axis in hippocampus-dependent learning and memory: Current state and future challenges. Neurosci Biobehav Rev. 2023; 152:105296. doi: 10.1016/j.neubiorev.2023.105296
Fan X, Zang T, Liu J, Wu N, Dai J, Bai J, et al. Changes in the gut microbiome in the first two years of life predicted the temperament in toddlers. J Affect Disord. 2023; 333:342–52. doi: 10.1016/j.jad.2023.04.073
Roth, W., Zadeh, K., Vekariya, R., Ge, Y. and Mohamadzadeh, M., 2021. Tryptophan metabolism and gut-brain homeostasis. Int J Mol Sci. 22(6):2973. doi: 10.3390/ijms22062973
Liu L, Wang H, Chen X, Zhang Y, Zhang H, Xie P. Gut microbiota and its metabolites in depression: From pathogenesis to treatment. EBioMedicine. 2023; 90:104527. doi: 10.1016/j.ebiom.2023.104527
Black CJ, Drossman DA, Talley NJ, Ruddy J, Ford AC. Functional gastrointestinal disorders: Advances in understanding and management. Lancet. 2020; 396(10263):1664–74. doi: 10.1016/S0140-6736(20)32115-2
Person H, Keefer L. Psychological comorbidity in gastrointestinal diseases: Update on the brain-gutmicrobiome axis. Prog Neuropsychopharmacol Biol Psychiatry. 2021; 107:110209. doi: 10.1016/j.pnpbp.2020.110209
Chen DL, Dai YC, Zheng L, Chen YL, Zhang YL, Tang ZP. Features of the gut microbiota in ulcerative colitis patients with depression: A pilot study. Medicine (Baltimore). 2021; 100(7): e24845. doi: 10.1097/MD.0000000000024845
Groen RN, De-Clercq NC, Nieuwdorp M, Hoenders HJR, Groen AK. Gut microbiota, metabolism and psychopathology: A critical review and novel perspectives. Crit Rev Clin Lab Sci. 2018; 55(4):283–93. doi: 10.1080/10408363.2018
Socała K, Doboszewska U, Szopa A, Serefko A, Włodarczyk M, Zielińska A, et al. The role of microbiota-gutbrain axis in neuropsychiatric and neurological disorders. Pharmacol Res. 2021; 172:105840. doi: 10.1016/j.phrs.2021.105840
Schumacher L, Klein JP, Elsaesser M, Härter M, Hautzinger M, Schramm E, et al. Implications of the network theory for the treatment of mental disorders: A secondary analysis of a randomized clinical trial. JAMA Psychiatry. 2023; e232823. doi: 10.1001/jamapsychiatry.2023.2823
Bertolín-Guillén JM. Psicopatología y el problema epistémico de la filosofía de la mente. [Psychopathology and the epistemic problem of philosophy of mind.] Norte Salud Ment. 2023; 19(69):47–55. https://aen.es/wp-content/uploads/2023/01/Norte-sm-69.pdf#page=47
Hunter S, Flaten E, Petersen C, Gervain J, Werker JF, Trainor LJ, et al. Babies, bugs and brains: How the early microbiome associates with infant brain and behavior development. PLoS One. 2023; 18(8): e0288689. doi: 10.1371/journal.pone.0288689
Querdasi FR, Enders C, Karnani N, Broekman B, Yap-Seng C, Gluckman PD, et al. Multigenerational adversity impacts on human gut microbiome composition and socioemotional functioning in early childhood. Proc Natl Acad Sci USA. 2023; 120(30): e2213768120. doi: 10.1073/pnas.2213768120
Bertolín-Guillén JM. Salud mental intergeneracional. [Intergenerational mental health.] Rev Neuropsiquiatr. 2023; 86(1):35–44. doi: 10.20453/rnp. v86i1.4465
Yuan X, Chen B, Duan Z, Xia Z, Ding Y, Chen T, et al. Depression and anxiety in patients with active ulcerative colitis: Crosstalk of gut microbiota, metabolomics and proteomics. Gut Microbes. 2021; 13(1):1987779. doi: 10.1080/19490976.2021.1987779
Xiao G, He Q, Liu L, Zhang T, Zhou M, Li X, et al. Causality of genetically determined metabolites on anxiety disorders: A two-sample Mendelian randomization study. J Transl Med. 2022; 20(1):475. doi: 10.1186/s12967-022-03691-2
Needham BD, Funabashi M, Adame MD, Wang Z, Boktor JC, Haney J, et al. A gut-derived metabolite alters brain activity and anxiety behaviour in mice. Nature. 2022; 602(7898):647–53. doi: 10.1038/s41586-022-04396-8
Simpson CA, Diaz-Arteche C, Eliby D, Schwartz OS, Simmons JG, Cowan CSM. The gut microbiota in anxiety and depression - A systematic review. Clin Psychol Rev. 2021; 83:101943. doi: 10.1016/j.cpr.2020.101943
Grau-del-Valle C, Fernández J, Solá E, Montoya-Castilla I, Morillas C, Bañuls C. Association between gut microbiota and psychiatric disorders: A systematic review. Front Psychol. 2023; 14:1215674. doi: 10.3389/fpsyg.2023.1215674
Butler MI, Bastiaanssen TFS, Long-Smith C, Morkl S, Berding K, Ritz NL, et al. The gut microbiome in social anxiety disorder: Evidence of altered composition and function. Transl Psychiatry. 2023; 13(1):95. doi: 10.1038/s41398-023-02325-5
Foster JA. Is anxiety associated with the gut microbiota? Mod Trends Psychiatry. 2021; 32:68–73. doi: 10.1159/000510418
Li Q, Zhang J, Gao Z, Zhang Y, Gu J. Gut microbiota-induced microRNA-206-3p increases anxiety-like behaviors by inhibiting expression of Cited2 and STK39. Microb Pathog. 2023; 176:106008. doi: 10.1016/j.micpath.2023.106008
Xiong RG, Li J, Cheng J, Zhou DD, Wu SX, Huang SY, et al. The role of gut microbiota in anxiety, depression, and other mental disorders as well as the protective effects of dietary components. Nutrients. 2023; 15(14):3258. doi: 10.3390/nu15143258
Qin X, Pan C, Cai Q, Zhao Y, He D, Wei W, et al. Assessing the effect of interaction between gut microbiome and inflammatory bowel disease on the risks of depression. Brain Behav Immun Health. 2022; 26:100557. doi: 10.1016/j.bbih.2022.100557
Haider MB, Basida B, Kaur J. Major depressive disorders in patients with inflammatory bowel disease and rheumatoid arthritis. World J Clin Cases. 2023; 11(4):764–79. doi: 10.12998/wjcc. v11.i4.764
Bhatt S, Kanoujia J, Mohana-Lakshmi S, Patil CR, Gupta G, Chellappan DK, et al. Role of brain-gut-microbiota axis in depression: Emerging therapeutic avenues. CNS Neurol Disord Drug Targets. 2023; 22(2):276–88. doi: 10.2174/1871527321666220329140804
Mudyanadzo TA, Hauzaree C, Yerokhina O, Architha NN, Ashqar HM. Irritable bowel syndrome and depression: A shared pathogenesis. Cureus. 2018; 10(8): e3178. doi: 10.7759/cureus.3178
Evrensel A, Ünsalver BÖ, Ceylan ME. Neuroinflammation, gut-brain axis and depression. Psychiatry Investig. 2020; 17(1):2–8. doi: 10.30773/pi.2019.08.09
Chang L, Wei Y, Hashimoto K. Brain-gut-microbiota axis in depression: A historical overview and future directions. Brain Res Bull. 2022; 182:44–56. doi: 10.1016/j.brainresbull.2022.02.004
Schreiber LS, Wozniak D, Scheller E, Böttcher E, Pelz JO, Schmidt FM. Enlarged cross-sectional area of the left vagus nerve in patients with major depressive disorder. Front Psychiatry. 2023; 14. doi: 10.3389/fpsyt.2023.1237983
Siopi E, Galerne M, Rivagorda M, Saha S, Moigneu C, Moriceau S, et al. Gut microbiota changes require vagus nerve integrity to promote depressive-like behaviors in mice. Mol Psychiatry. 2023. doi: 10.1038/s41380-023-02071-6
Fracas E, Costantino A, Vecchi M, Buoli M. Depressive and anxiety disorders in patients with inflammatory bowel diseases: Are there any gender differences? Int J Environ Res Public Health. 2023; 20(13):6255. doi: 10.3390/ijerph20136255
Yao H, Zhang D, Yu H, Shen H, Liu H, Meng F, et al. The microbiota-gut-brain axis in pathogenesis of depression: A narrative review. Physiol Behav. 2023; 260:114056. doi: 10.1016/j.physbeh.2022.114056
Scaldaferri F, D'Onofrio AM, Calia R, Di-Vincenzo F, Ferrajoli GF, Petito V, et al. Gut microbiota signatures are associated with psychopathological profiles in patients with ulcerative colitis: Results from an Italian tertiary IBD center. Inflamm Bowel Dis. 2023; izad091. doi: 10.1093/ibd/izad091
Lasheras I, Gracia-García P, Santabárbara J. Modulation of gut microbiota in autism spectrum disorders: A systematic review. Eur J Psychiatry. 2021; 35(2):107–21. doi: 10.1016/j.ejpsy.2020.12.003 280 Bertolín-Guillén, J. M. (2023). Microbiota-Gut-Brain Axis and Mental Health. British Journal of Healthcare and Medical Research, Vol - 10(6). 270-
Yoshikawa S, Taniguchi K, Sawamura H, Ikeda Y, Tsuji A, Matsuda S. A new concept of associations between gut microbiota, immunity and central nervous system for the innovative treatment of neurodegenerative disorders. Metabolites. 2022; 12(11):1052. doi: 10.3390/metabo12111052
Zhou H, Wang K, Xu Z, Liu D, Wang Y, Guo M. Chronic unpredictable stress induces depression/anxietyrelated behaviors and alterations of hippocampal monoamine receptor mRNA expression in female mice at different ages. Heliyon. 2023; 9(7): e18369. doi: 10.1016/j.heliyon. 2023.e18369
Nikolova VL, Smith MRB, Hall LJ, Cleare AJ, Stone JM, Young AH. Perturbations in gut microbiota composition in psychiatric disorders: A review and meta-analysis. JAMA Psychiatry. 2021; 78(12):1343–54. doi: 10.1001/jamapsychiatry.2021.2573. Erratum in: JAMA Psychiatry. 2022; 79(12):1241.
Gao J, Zhao L, Cheng Y, Lei W, Wang Y, Liu X, et al. Probiotics for the treatment of depression and its comorbidities: A systemic review. Front Cell Infect Microbiol. 2023; 13:1167116. doi: 10.3389/fcimb.2023.1167116
Xu F, Xie Q, Kuang W, Dong Z. Interactions between antidepressants and intestinal microbiota. Neurotherapeutics. 2023; 20(2):359–71. doi: 10.1007/s13311-023-01362-8
Irum N, Afzal T, Faraz MH, Aslam Z, Rasheed F. The role of gut microbiota in depression: An analysis of the gut-brain axis. Front Behav Neurosci. 2023; 17:1185522. doi: 10.3389/fnbeh.2023.1185522
Rehman MU, Ghazanfar S, Ul-Haq R, Ullah S, Khan S, Wu J, et al. Probiotics (Bacillus clausii and Lactobacillus fermentum NMCC-14) ameliorate stress behavior in mice by increasing monoamine levels and mRNA expression of dopamine receptors (D1 and D2) and synaptophysin. Front Pharmacol. 2022; 13:915595. doi: 10.3389/fphar.2022.915595
Wilmes L, Collins JM, O'Riordan KJ, O'Mahony SM, Cryan JF, Clarke G. Of bowels, brain and behavior: A role for the gut microbiota in psychiatric comorbidities in irritable bowel syndrome. Neurogastroenterol Motil. 2021; 33(3): e14095. doi: 10.1111/nmo.14095
Imdad A, Pandit NG, Zaman M, Minkoff NZ, Tanner-Smith EE, Gomez-Duarte OG, et al. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev. 2023; 4(4):CD012774. doi: 10.1002/14651858.CD012774.pub3
Rudzki L, Stone TW, Maes M, Misiak B, Samochowiec J, Szulc A. Gut microbiota-derived vitamins -underrated powers of a multipotent ally in psychiatric health and disease. Prog Neuropsychopharmacol Biol Psychiatry. 2021; 107:110240. doi: 10.1016/j.pnpbp.2020.110240
Nohesara S, Abdolmaleky HM, Thiagalingam S. Epigenetic aberrations in major psychiatric diseases related to diet and gut microbiome alterations. Genes (Basel). 2023; 14(7):1506. doi: 10.3390/genes14071506
Alam R, Abdolmaleky HM, Zhou JR. Microbiome, inflammation, epigenetic alterations, and mental diseases. Am J Med Genet B Neuropsychiatr Genet. 2017; 174(6):651–60. doi: 10.1002/ajmg.b.32567
Peedicayil J. Genome-environment interactions and psychiatric disorders. Biomedicines. 2023; 11(4):1209. doi: 10.3390/biomedicines11041209
Philippou A, Sehgal P, Ungaro RC, Wang K, Bagiella E, Dubinsky MC, et al. High levels of psychological resilience are associated with decreased anxiety in inflammatory bowel disease. Inflamm Bowel Dis. 2022; 28(6):888–94. doi: 10.1093/ibd/izab200
Drossman, D.A., Tack, J., Ford, A.C., Szigethy, E., Törnblom, H. and van- Drossman DA, Tack J, Ford AC, Szigethy E, Törnblom H, Van Oudenhove L. Neuromodulators for functional gastrointestinal disorders (disorders of gut-brain interaction): A Rome foundation working team report. Gastroenterology. 2018; 154(4):1140–71. e1. doi: 10.1053/j.gastro.2017.11.279 281
Staudacher HM, Black CJ, Teasdale SB, Mikocka-Walus A, Keefer L. Irritable bowel syndrome and mental health comorbidity - approach to multidisciplinary management. Nat Rev Gastroenterol Hepatol. 2023; 20(9):582–96. doi: 10.1038/s41575-023-00794-z
Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, Martin M, De-la-Vega-Correa L, Zapata C, et al. Microbiota alterations in proline metabolism impact depression. Cell Metab. 2022; 34(5):681–701.e10. doi: 10.1016/j.cmet.2022.04.001
Wang M, Liu W, Ge J, Liu S. The immunomodulatory mechanisms for acupuncture practice. Front Immunol. 2023; 14:1147718. doi: 10.3389/fimmu.2023.1147718
Sun Z, Wang X, Feng S, Xie C, Xing Y, Guo L, et al. A review of neuroendocrine immune system abnormalities in IBS based on the brain-gut axis and research progress of acupuncture intervention. Front Neurosci. 2023; 17:934341. doi: 10.3389/fnins.2023.934341
Gharby C, Foster D, Kioutchoukova I, Lucke-Wold BP. Acupuncture, nutritional augmentation, and physical rehabilitation: Improving recovery following spinal fusion. OSP J Neurol Neurolog Dis. 2023; 1(1):1–13. ttps://www.ospublishers.com/pdf/NND-1-102.pdf
Bertolín-Guillén JM. Psychotherapies in current clinical psychology and psychiatry in Spain. Rev Psiquiatr Salud Ment (engl ed). 2020; S1888-9891(20)30023-9. doi: 10.1016/j.rpsm.2020.01.004
Bertolín-Guillén JM. Current state of psychopharmacology, psychotherapies and other interventions in mental health problems and disorders. Eur J Appl Sci. 2021; 9(5):251–61. doi: 10.14738/aivp.95.10994
Zhang X, Mao F, Li Y, Wang J, Wu L, Sun J, et al. Effects of a maternal mindfulness intervention targeting prenatal psychological distress on infants' meconium microbiota: A randomized controlled trial. Psychoneuroendocrinology. 2022; 145:105913. doi: 10.1016/j.psyneuen.2022.105913
Wang Z, Liu S, Xu X, Xiao Y, Yang M, Zhao X, et al. Gut microbiota associated with effectiveness and responsiveness to mindfulness-based cognitive therapy in improving trait anxiety. Front Cell Infect Microbiol. 2022; 12:719829. doi: 10.3389/fcimb.2022.719829
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