Skip to content
2000
image of The Gut Microbiota-anxiety Connection: Evidence, Mechanisms, and Therapeutic Strategies

Abstract

The gut-brain axis (GBA), a bidirectional communication system between the gut and the brain, has emerged as a critical player in mental health. The interest in the connection between anxiety disorders (AD) and the gut microbiota is growing. This paper provides an overview of gut microbiota’s role in dysregulation in anxiety, including alterations in gut microbiota (dysbiosis), leaky gut, metabolic endotoxemia, and the effect of antipsychotic medications. The mechanisms underlying the gut microbiota-anxiety (GMA) connection, such as neurotransmitter production, immune dysregulation, and GBA communication, are discussed. Furthermore, the paper explores gut microbiota-based therapeutic strategies, including probiotics, prebiotics, symbiotics, fecal microbiota transplantation, and dietary interventions, as potential approaches for anxiety management. This research field's clinical implications and future directions are also examined, underscoring that more studies are needed on gut microbiota’s role in anxiety disorders. The conclusion highlights the importance of this ongoing research and the potential for personalized therapeutic interventions, instilling hope and optimism for the future of anxiety management and providing reassurance about the potential for personalized therapeutic interventions in this field.

Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673356125250409182218
2025-04-25
2025-09-07
Loading full text...

Full text loading...

References

  1. Antos Z. Zackiewicz K. Tomaszek N. Modzelewski S. Waszkiewicz N. Beyond pharmacology: A narrative review of alternative therapies for anxiety disorders. Diseases 2024 12 9 216 10.3390/diseases12090216 39329885
    [Google Scholar]
  2. Teesson M. Mitchell P.B. Deady M. Memedovic S. Slade T. Baillie A. Affective and anxiety disorders and their relationship with chronic physical conditions in Australia: Findings of the 2007 national survey of mental health and wellbeing. Aust. N. Z. J. Psychiatry 2011 45 11 939 946 10.3109/00048674.2011.614590 21967412
    [Google Scholar]
  3. Pathak Y.V. Pathak S. Stough C. Anxiety, gut microbiome, and nutraceuticals: Recent trends and clinical evidence. CRC Press Boca Raton 2023 10.1201/9781003333821
    [Google Scholar]
  4. Generoso J.S. Giridharan V.V. Lee J. Macedo D. Barichello T. The role of the microbiota-gut-brain axis in neuropsychiatric disorders. Br. J. Psychiatry 2021 43 3 293 305 10.1590/1516‑4446‑2020‑0987 32667590
    [Google Scholar]
  5. Rutsch A. Kantsjö J.B. Ronchi F. The gut-brain axis: How microbiota and host inflammasome influence brain physiology and pathology. Front. Immunol. 2020 11 604179 10.3389/fimmu.2020.604179 33362788
    [Google Scholar]
  6. Curti C.F. Bossolani J.A. Camargo R.A. Caramelo A.A.F. Silva M.G.L. Favaro M.E.F. Soncin L.V. Ismael L. Costa M.C.S. Marim A.G. Dolci C.E.M. Bosso H. The gut-brain axis: Exploring the role of microbiota in depression and anxiety disorder. Int. J. Health Sci. 2024 4 26 2 13 10.22533/at.ed.1594262418038
    [Google Scholar]
  7. Socała K. Doboszewska U. Szopa A. Serefko A. Włodarczyk M. Zielińska A. Poleszak E. Fichna J. Wlaź P. The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders. Pharmacol. Res. 2021 172 105840 10.1016/j.phrs.2021.105840 34450312
    [Google Scholar]
  8. Montagnani M. Bottalico L. Potenza M.A. Charitos I.A. Topi S. Colella M. Santacroce L. The crosstalk between gut microbiota and nervous system: A bidirectional interaction between microorganisms and metabolome. Int. J. Mol. Sci. 2023 24 12 10322 10.3390/ijms241210322 37373470
    [Google Scholar]
  9. Wang H. Zhao T. Liu Z. Danzengquzhen Cisangzhuoma Ma J. Li X. Huang X. Li B. The neuromodulatory effects of flavonoids and gut microbiota through the gut-brain axis. Front. Cell. Infect. Microbiol. 2023 13 1197646 10.3389/fcimb.2023.1197646 37424784
    [Google Scholar]
  10. Mediavilla C. Bidirectional gut-brain communication: A role for orexin-A. Neurochem. Int. 2020 141 104882 10.1016/j.neuint.2020.104882 33068686
    [Google Scholar]
  11. Petra A.I. Panagiotidou S. Hatziagelaki E. Stewart J.M. Conti P. Theoharides T.C. Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin. Ther. 2015 37 5 984 995 10.1016/j.clinthera.2015.04.002 26046241
    [Google Scholar]
  12. Thion M.S. Low D. Silvin A. Chen J. Grisel P. Schulte-Schrepping J. Blecher R. Ulas T. Squarzoni P. Hoeffel G. Microbiome influences prenatal and adult microglia in a sex-specific manner. Cell 2018 172 3 500 516 10.1016/j.cell.2017.11.042 29275859
    [Google Scholar]
  13. Erny D. Hrabě de Angelis A.L. Jaitin D. Wieghofer P. Staszewski O. David E. Keren-Shaul H. Mahlakoiv T. Jakobshagen K. Buch T. Schwierzeck V. Utermöhlen O. Chun E. Garrett W.S. McCoy K.D. Diefenbach A. Staeheli P. Stecher B. Amit I. Prinz M. Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci. 2015 18 7 965 977 10.1038/nn.4030 26030851
    [Google Scholar]
  14. Sperandio V. Torres A.G. Jarvis B. Nataro J.P. Kaper J.B. Bacteria–host communication: The language of hormones. Proc. Natl. Acad. Sci. USA 2003 100 15 8951 8956 10.1073/pnas.1537100100 12847292
    [Google Scholar]
  15. Yeo S. Park H. Ji Y. Park S. Yang J. Lee J. Mathara J.M. Shin H. Holzapfel W. Influence of gastrointestinal stress on autoinducer-2 activity of two Lactobacillus species. FEMS Microbiol. Ecol. 2015 91 7 fiv065 10.1093/femsec/fiv065 26092949
    [Google Scholar]
  16. Sacoor C. Marugg J.D. Lima N.R. Empadinhas N. Montezinho L. Gut-brain axis impact on canine anxiety disorders: New challenges for behavioral veterinary medicine. Vet. Med. Int. 2024 2024 1 2856759 10.1155/2024/2856759 38292207
    [Google Scholar]
  17. Malan-Muller S. Valles-Colomer M. Raes J. Lowry C.A. Seedat S. Hemmings S.M.J. The gut microbiome and mental health: Implications for anxiety-and trauma-related disorders. OMICS 2018 22 2 90 107 10.1089/omi.2017.0077 28767318
    [Google Scholar]
  18. Lydiard R.B. The role of GABA in anxiety disorders. J. Clin. Psychiatry 2003 64 Suppl. 3 21 27 12662130
    [Google Scholar]
  19. Wu J.T. Sun C.L. Lai T.T. Liou C.W. Lin Y.Y. Xue J.Y. Wang H.W. Chai L.M.X. Lee Y.J. Chen S.L. Chang A.Y.W. Hung J.H. Hsu C.C. Wu W.L. Oral short-chain fatty acids administration regulates innate anxiety in adult microbiome-depleted mice. Neuropharmacology 2022 214 109140 10.1016/j.neuropharm.2022.109140 35613660
    [Google Scholar]
  20. Yang D.F. Huang W.C. Wu C.W. Huang C.Y. Yang Y.C.S.H. Tung Y.T. Acute sleep deprivation exacerbates systemic inflammation and psychiatry disorders through gut microbiota dysbiosis and disruption of circadian rhythms. Microbiol. Res. 2023 268 127292 10.1016/j.micres.2022.127292 36608535
    [Google Scholar]
  21. Bravo J.A. Julio-Pieper M. Forsythe P. Kunze W. Dinan T.G. Bienenstock J. Cryan J.F. Communication between gastrointestinal bacteria and the nervous system. Curr. Opin. Pharmacol. 2012 12 6 667 672 10.1016/j.coph.2012.09.010 23041079
    [Google Scholar]
  22. Chakrabarti A. Geurts L. Hoyles L. Iozzo P. Kraneveld A.D. La Fata G. Miani M. Patterson E. Pot B. Shortt C. Vauzour D. The microbiota–gut–brain axis: Pathways to better brain health. Perspectives on what we know, what we need to investigate and how to put knowledge into practice. Cell. Mol. Life Sci. 2022 79 2 80 10.1007/s00018‑021‑04060‑w 35044528
    [Google Scholar]
  23. Anand N. Gorantla V.R. Chidambaram S.B. The role of gut dysbiosis in the pathophysiology of neuropsychiatric disorders. Cells 2022 12 1 54 10.3390/cells12010054 36611848
    [Google Scholar]
  24. Milà-Guasch M. Ramírez S. Llana S.R. Fos-Domènech J. Dropmann L.M. Pozo M. Eyre E. Gómez-Valadés A.G. Obri A. Haddad-Tóvolli R. Claret M. Maternal emulsifier consumption programs offspring metabolic and neuropsychological health in mice. PLoS Biol. 2023 21 8 e3002171 10.1371/journal.pbio.3002171 37616199
    [Google Scholar]
  25. Leigh S.J. Uhlig F. Wilmes L. Sanchez-Diaz P. Gheorghe C.E. Goodson M.S. Kelley-Loughnane N. Hyland N.P. Cryan J.F. Clarke G. The impact of acute and chronic stress on gastrointestinal physiology and function: A microbiota–gut–brain axis perspective. J. Physiol. 2023 601 20 4491 4538 10.1113/JP281951 37756251
    [Google Scholar]
  26. Xiao Q. Shu R. Wu C. Tong Y. Xiong Z. Zhou J. Yu C. Xie X. Fu Z. Crocin-I alleviates the depression-like behaviors probably via modulating “microbiota-gut-brain” axis in mice exposed to chronic restraint stress. J. Affect. Disord. 2020 276 476 486 10.1016/j.jad.2020.07.041 32871679
    [Google Scholar]
  27. Bercik P. Collins S.M. The effects of inflammation, infection and antibiotics on the microbiota-gut-brain axis. Adv. Exp. Med. Biol. 2014 817 279 289 10.1007/978‑1‑4939‑0897‑4_13 24997039
    [Google Scholar]
  28. Baumel W.T. Mills J.A. Schroeder H.K. Neptune Z. Levine A. Strawn J.R. Gastrointestinal symptoms in pediatric patients with anxiety disorders and their relationship to selective serotonin reuptake inhibitor treatment or placebo. Child Psychiatry Hum. Dev. 2023 10.1007/s10578‑023‑01586‑x 37659029
    [Google Scholar]
  29. Baske M.M. Timmerman K.C. Garmo L.G. Freitas M.N. McCollum K.A. Ren T.Y. Fecal microbiota transplant on Escherichia-Shigella gut composition and its potential role in the treatment of generalized anxiety disorder: A systematic review. J. Affect. Disord. 2024 354 309 317 10.1016/j.jad.2024.03.088 38499070
    [Google Scholar]
  30. Aslam H. Green J. Jacka F.N. Collier F. Berk M. Pasco J. Dawson S.L. Fermented foods, the gut and mental health: A mechanistic overview with implications for depression and anxiety. Nutr. Neurosci. 2020 23 9 659 671 10.1080/1028415X.2018.1544332 30415609
    [Google Scholar]
  31. Wasiak J. Gawlik-Kotelnicka O. Intestinal permeability and its significance in psychiatric disorders – A narrative review and future perspectives. Behav. Brain Res. 2023 448 114459 10.1016/j.bbr.2023.114459 37121278
    [Google Scholar]
  32. Juruena M.F. Eror F. Cleare A.J. Young A.H. The role of early life stress in HPA axis and anxiety. Anxiety Disorders. Advances in Experimental Medicine and Biology; Kim, Y.K., Ed Springer Singapore 2020 Vol. 1191 141 153
    [Google Scholar]
  33. Yoon S. Kim Y.-K. The role of the oxytocin system in anxiety disorders. Adv. Exp. Med. Biol. 2020 1191 103 120 10.1007/978‑981‑32‑9705‑0_7 32002925
    [Google Scholar]
  34. Felice D. GABAB receptors: Anxiety and mood disorders Curr. Top. Behav. Neurosci. 2022 52 241 265 10.1007/7854_2020_171 32860591
    [Google Scholar]
  35. Nikolaus S. Antke C. Beu M. Müller H.W. Cortical GABA, striatal dopamine and midbrain serotonin as the key players in compulsive and anxiety disorders--Results from in vivo imaging studies. Rev. Neurosci. 2010 21 2 119 139 10.1515/REVNEURO.2010.21.2.119 20614802
    [Google Scholar]
  36. Krieger J.P. Asker M. van der Velden P. Börchers S. Richard J.E. Maric I. Longo F. Singh A. de Lartigue G. Skibicka K.P. Neural pathway for gut feelings: Vagal interoceptive feedback from the gastrointestinal tract is a critical modulator of anxiety-like behavior. Biol. Psychiatry 2022 92 9 709 721 10.1016/j.biopsych.2022.04.020 35965105
    [Google Scholar]
  37. Xia G. Han Y. Meng F. He Y. Srisai D. Farias M. Dang M. Palmiter R.D. Xu Y. Wu Q. Reciprocal control of obesity and anxiety–depressive disorder via a GABA and serotonin neural circuit. Mol. Psychiatry 2021 26 7 2837 2853 10.1038/s41380‑021‑01053‑w 33767348
    [Google Scholar]
  38. Jindal A. Mahesh R. Kumar B. Anxiolytic-like effect of linezolid in experimental mouse models of anxiety. Prog. Neuropsychopharmacol. Biol. Psychiatry 2013 40 47 53 10.1016/j.pnpbp.2012.09.006 23021974
    [Google Scholar]
  39. Schmidtner A.K. Slattery D.A. Gläsner J. Hiergeist A. Gryksa K. Malik V.A. Hellmann-Regen J. Heuser I. Baghai T.C. Gessner A. Rupprecht R. Di Benedetto B. Neumann I.D. Minocycline alters behavior, microglia and the gut microbiome in a trait-anxiety-dependent manner. Transl. Psychiatry 2019 9 1 223 10.1038/s41398‑019‑0556‑9 31519869
    [Google Scholar]
  40. Glover M.E. Cohen J.L. Singer J.R. Sabbagh M.N. Rainville J.R. Hyland M.T. Morrow C.D. Weaver C.T. Hodes G.E. Kerman I.A. Clinton S.M. Examining the role of microbiota in emotional behavior: Antibiotic treatment exacerbates anxiety in high anxiety-prone male rats. Neuroscience 2021 459 179 197 10.1016/j.neuroscience.2021.01.030 33540050
    [Google Scholar]
  41. Majidi J. Kosari-Nasab M. Salari A.A. Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice. Brain Res. Bull. 2016 120 1 13 10.1016/j.brainresbull.2015.10.009 26521068
    [Google Scholar]
  42. Kim S.Y. Woo S.Y. Raza S. Ho D. Jeon S.W. Chang Y. Ryu S. Kim H.L. Kim H.N. Association between gut microbiota and anxiety symptoms: A large population-based study examining sex differences. J. Affect. Disord. 2023 333 21 29 10.1016/j.jad.2023.04.003 37031878
    [Google Scholar]
  43. Nikolova V.L. Smith M.R.B. Hall L.J. Cleare A.J. Stone J.M. Young A.H. Perturbations in gut microbiota composition in psychiatric disorders: A review and meta-analysis. JAMA Psychiatry 2021 78 12 1343 1354 10.1001/jamapsychiatry.2021.2573 34524405
    [Google Scholar]
  44. Gasmi A. Bjørklund G. Mujawdiya P.K. Semenova Y. Dosa A. Piscopo S. Pen J.J. Benahmed A.G. Costea D.O. Gut microbiota in bariatric surgery. Crit. Rev. Food Sci. Nutr. 2023 63 28 9299 9314 10.1080/10408398.2022.2067116 35531940
    [Google Scholar]
  45. Bear T.L.K. Dalziel J.E. Coad J. Roy N.C. Butts C.A. Gopal P.K. The role of the gut microbiota in dietary interventions for depression and anxiety. Adv. Nutr. 2020 11 4 890 907 10.1093/advances/nmaa016 32149335
    [Google Scholar]
  46. Cryan J.F. Dinan T.G. Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 2012 13 10 701 712 10.1038/nrn3346 22968153
    [Google Scholar]
  47. Ansari F. Pourjafar H. Tabrizi A. Homayouni A. The effects of probiotics and prebiotics on mental disorders: A review on depression, anxiety, Alzheimer, and autism spectrum disorders. Curr. Pharm. Biotechnol. 2020 21 7 555 565 10.2174/1389201021666200107113812 31914909
    [Google Scholar]
  48. Liu R.T. Walsh R.F.L. Sheehan A.E. Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials. Neurosci. Biobehav. Rev. 2019 102 13 23 10.1016/j.neubiorev.2019.03.023 31004628
    [Google Scholar]
  49. Simpson C.A. Diaz-Arteche C. Eliby D. Schwartz O.S. Simmons J.G. Cowan C.S.M. The gut microbiota in anxiety and depression – A systematic review. Clin. Psychol. Rev. 2021 83 101943 10.1016/j.cpr.2020.101943 33271426
    [Google Scholar]
  50. Wiley N.C. Dinan T.G. Ross R.P. Stanton C. Clarke G. Cryan J.F. The microbiota-gut-brain axis as a key regulator of neural function and the stress response: Implications for human and animal health. J. Anim. Sci. 2017 95 7 3225 3246 28727115
    [Google Scholar]
  51. Kuti D. Winkler Z. Horváth K. Juhász B. Paholcsek M. Stágel A. Gulyás G. Czeglédi L. Ferenczi S. Kovács K.J. Gastrointestinal (non-systemic) antibiotic rifaximin differentially affects chronic stress-induced changes in colon microbiome and gut permeability without effect on behavior. Brain Behav. Immun. 2020 84 218 228 10.1016/j.bbi.2019.12.004 31821847
    [Google Scholar]
  52. Cani P.D. Bibiloni R. Knauf C. Waget A. Neyrinck A.M. Delzenne N.M. Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008 57 6 1470 1481 10.2337/db07‑1403 18305141
    [Google Scholar]
  53. On Wah D.T. Kavaliers M. Bishnoi I.R. Ossenkopp K.P. Lipopolysaccharide (LPS) induced sickness in early adolescence alters the behavioral effects of the short-chain fatty acid, propionic acid, in late adolescence and adulthood: Examining anxiety and startle reactivity. Behav. Brain Res. 2019 360 312 322 10.1016/j.bbr.2018.12.003 30521932
    [Google Scholar]
  54. Hsiao E.Y. McBride S.W. Hsien S. Sharon G. Hyde E.R. McCue T. Codelli J.A. Chow J. Reisman S.E. Petrosino J.F. The microbiota modulates gut physiology and behavioral abnormalities associated with autism. Cell 2013 155 7 1451 10.1016/j.cell.2013.11.024 24315484
    [Google Scholar]
  55. Bernstein C.N. The brain-gut axis and stress in inflammatory bowel disease. Gastroenterol. Clin. North Am. 2017 46 4 839 846 10.1016/j.gtc.2017.08.006 29173525
    [Google Scholar]
  56. El-Hakim Y. Bake S. Mani K.K. Sohrabji F. Impact of intestinal disorders on central and peripheral nervous system diseases. Neurobiol. Dis. 2022 165 105627 10.1016/j.nbd.2022.105627 35032636
    [Google Scholar]
  57. Stilling R.M. Ryan F.J. Hoban A.E. Shanahan F. Clarke G. Claesson M.J. Dinan T.G. Cryan J.F. Microbes & neurodevelopment – Absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala. Brain Behav. Immun. 2015 50 209 220 10.1016/j.bbi.2015.07.009 26184083
    [Google Scholar]
  58. Bear T. Dalziel J. Coad J. Roy N. Butts C. Gopal P. The microbiome-gut-brain axis and resilience to developing anxiety or depression under stress. Microorganisms 2021 9 4 723 10.3390/microorganisms9040723 33807290
    [Google Scholar]
  59. Fields C.T. Chassaing B. Castillo-Ruiz A. Osan R. Gewirtz A.T. de Vries G.J. Effects of gut-derived endotoxin on anxiety-like and repetitive behaviors in male and female mice. Biol. Sex Differ. 2018 9 1 7 10.1186/s13293‑018‑0166‑x 29351816
    [Google Scholar]
  60. Łoś K. Waszkiewicz N. Biological markers in anxiety disorders. J. Clin. Med. 2021 10 8 1744 10.3390/jcm10081744 33920547
    [Google Scholar]
  61. Giollabhui N.M. Slaney C. Hemani G. Foley E. van der Most P. Nolte I. Snieder H. Smith G.D. Khandaker G. Hartman C. Role of inflammation in depressive and anxiety disorders, affect, and cognition: Genetic and non-genetic findings in the lifelines cohort study. medRxiv 2024
    [Google Scholar]
  62. van Eeden W.A. El Filali E. van Hemert A.M. Carlier I.V.E. Penninx B.W.J.H. Lamers F. Schoevers R. Giltay E.J. Basal and LPS-stimulated inflammatory markers and the course of anxiety symptoms. Brain Behav. Immun. 2021 98 378 387 10.1016/j.bbi.2021.09.001 34509625
    [Google Scholar]
  63. Feng X.Z. Li Z. Li Z.Y. Wang K. Tan X. Zhao Y.Y. Mi W.F. Zhu W.L. Bao Y.P. Lu L. Li S.X. Effectiveness and safety of second-generation antipsychotics for psychiatric disorders apart from schizophrenia: A systematic review and meta-analysis. Psychiatry Res. 2024 332 115637 10.1016/j.psychres.2023.115637 38150810
    [Google Scholar]
  64. Thronson L.R. Pagalilauan G.L. Psychopharmacology. Med. Clin. North Am. 2014 98 5 927 958 10.1016/j.mcna.2014.06.001 25134867
    [Google Scholar]
  65. McGuinness A.J. Davis J.A. Dawson S.L. Loughman A. Collier F. O’Hely M. Simpson C.A. Green J. Marx W. Hair C. Guest G. Mohebbi M. Berk M. Stupart D. Watters D. Jacka F.N. A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia. Mol. Psychiatry 2022 27 4 1920 1935 10.1038/s41380‑022‑01456‑3 35194166
    [Google Scholar]
  66. Zeng C. Yang P. Cao T. Gu Y. Li N. Zhang B. Xu P. Liu Y. Luo Z. Cai H. Gut microbiota: An intermediary between metabolic syndrome and cognitive deficits in schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 2021 106 110097 10.1016/j.pnpbp.2020.110097 32916223
    [Google Scholar]
  67. Dias M.F. Nogueira Y.J.A. Romano-Silva M.A. Marques de Miranda D. Effects of antipsychotics on the gastrointestinal microbiota: A systematic review. Psychiatry Res. 2024 336 115914 10.1016/j.psychres.2024.115914 38663221
    [Google Scholar]
  68. Tomizawa Y. Kurokawa S. Ishii D. Miyaho K. Ishii C. Sanada K. Fukuda S. Mimura M. Kishimoto T. Effects of psychotropics on the microbiome in patients with depression and anxiety: Considerations in a naturalistic clinical setting. Int. J. Neuropsychopharmacol. 2021 24 2 97 107 10.1093/ijnp/pyaa070 32975292
    [Google Scholar]
  69. Zhang Y. Fan Q. Hou Y. Zhang X. Yin Z. Cai X. Wei W. Wang J. He D. Wang G. Yuan Y. Hao H. Zheng X. Bacteroides species differentially modulate depression-like behavior via gut-brain metabolic signaling. Brain Behav. Immun. 2022 102 11 22 10.1016/j.bbi.2022.02.007 35143877
    [Google Scholar]
  70. Duranti S. Ruiz L. Lugli G.A. Tames H. Milani C. Mancabelli L. Mancino W. Longhi G. Carnevali L. Sgoifo A. Margolles A. Ventura M. Ruas-Madiedo P. Turroni F. Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA. Sci. Rep. 2020 10 1 14112 10.1038/s41598‑020‑70986‑z 32839473
    [Google Scholar]
  71. Zhu R. Fang Y. Li H. Liu Y. Wei J. Zhang S. Wang L. Fan R. Wang L. Li S. Chen T. Psychobiotic Lactobacillus plantarum JYLP-326 relieves anxiety, depression, and insomnia symptoms in test anxious college via modulating the gut microbiota and its metabolism. Front. Immunol. 2023 14 1158137 10.3389/fimmu.2023.1158137 37033942
    [Google Scholar]
  72. Liu P. Liu Z. Wang J. Wang J. Gao M. Zhang Y. Yang C. Zhang A. Li G. Li X. Liu S. Liu L. Sun N. Zhang K. Immunoregulatory role of the gut microbiota in inflammatory depression. Nat. Commun. 2024 15 1 3003 10.1038/s41467‑024‑47273‑w 38589368
    [Google Scholar]
  73. Huang F. Wu X. Brain neurotransmitter modulation by gut microbiota in anxiety and depression. Front. Cell Dev. Biol. 2021 9 649103 10.3389/fcell.2021.649103 33777957
    [Google Scholar]
  74. Takayanagi Y. Onaka T. Roles of oxytocin in stress responses, allostasis and resilience. Int. J. Mol. Sci. 2021 23 1 150 10.3390/ijms23010150 35008574
    [Google Scholar]
  75. Allen M.J. GABA Receptor StatPearls Treasure Island, FL Statpearls Publishing 2025
    [Google Scholar]
  76. Dresp-Langley B. From reward to anhedonia-dopamine function in the global mental health context. Biomedicines 2023 11 9 2469 10.3390/biomedicines11092469 37760910
    [Google Scholar]
  77. Albert P.R. Vahid-Ansari F. Luckhart C. Serotonin-prefrontal cortical circuitry in anxiety and depression phenotypes: Pivotal role of pre- and post-synaptic 5-HT1A receptor expression. Front. Behav. Neurosci. 2014 8 199 10.3389/fnbeh.2014.00199 24936175
    [Google Scholar]
  78. Liu G. Chong H.X. Chung F.Y.L. Li Y. Liong M.T. Lactobacillus plantarum DR7 modulated bowel movement and gut microbiota associated with dopamine and serotonin pathways in stressed adults. Int. J. Mol. Sci. 2020 21 13 4608 10.3390/ijms21134608 32610495
    [Google Scholar]
  79. Bhatia N.Y. Jalgaonkar M.P. Hargude A.B. Sherje A.P. Oza M.J. Doshi G.M. Gut-brain axis and neurological disorders-how microbiomes affect our mental health. CNS Neurol. Disord. Drug Targets 2023 22 7 1008 1030 10.2174/1871527321666220822172039 36017855
    [Google Scholar]
  80. O’Mahony S.M. Clarke G. Borre Y.E. Dinan T.G. Cryan J.F. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav. Brain Res. 2015 277 32 48 10.1016/j.bbr.2014.07.027 25078296
    [Google Scholar]
  81. Mhanna A. Martini N. Hmaydoosh G. Hamwi G. Jarjanazi M. Zaifah G. Kazzazo R. Haji Mohamad A. Alshehabi Z. The correlation between gut microbiota and both neurotransmitters and mental disorders: A narrative review. Medicine 2024 103 5 e37114 10.1097/MD.0000000000037114 38306525
    [Google Scholar]
  82. Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Res. 2018 1693 Pt B 128 133 10.1016/j.brainres.2018.03.015 29903615
    [Google Scholar]
  83. Zanoli L. Tuttolomondo A. Inserra G. Cappello M. Granata A. Malatino L. Castellino P. Anxiety, depression, chronic inflammation and aortic stiffness in Crohn’s disease: The brain--Gut--vascular axis. J. Hypertens. 2020 38 10 2008 2017 10.1097/HJH.0000000000002517 32890277
    [Google Scholar]
  84. Skowrońska A. Gawlik-Kotelnicka O. Margulska A. Strzelecki D. The influence of probiotic supplementation on the severity of anxiety and depressive symptoms; Function and composition of gut microbiota; and metabolic, inflammation, and oxidative stress markers in patients with depression—A study protocol. Metabolites 2023 13 2 182 10.3390/metabo13020182 36837799
    [Google Scholar]
  85. Cheng J. Hu H. Ju Y. Liu J. Wang M. Liu B. Zhang Y. Gut microbiota-derived short-chain fatty acids and depression: Deep insight into biological mechanisms and potential applications. Gen. Psychiatr. 2024 37 1 e101374 10.1136/gpsych‑2023‑101374 38390241
    [Google Scholar]
  86. Patterson T.T. Grandhi R. Gut microbiota and neurologic diseases and injuries. Adv. Exp. Med. Biol. 2020 1238 73 91 10.1007/978‑981‑15‑2385‑4_6 32323181
    [Google Scholar]
  87. Stevens B.R. Goel R. Seungbum K. Richards E.M. Holbert R.C. Pepine C.J. Raizada M.K. Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression. Gut 2018 67 8 1555.2 1557 10.1136/gutjnl‑2017‑314759 28814485
    [Google Scholar]
  88. Zhang K. Chen L. Yang J. Liu J. Li J. Liu Y. Li X. Chen L. Hsu C. Zeng J. Xie X. Wang Q. Gut microbiota-derived short-chain fatty acids ameliorate methamphetamine-induced depression- and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner. Acta Pharm. Sin. B 2023 13 12 4801 4822 10.1016/j.apsb.2023.09.010 38045052
    [Google Scholar]
  89. Moțățăianu A. Șerban G. Andone S. The role of short-chain fatty acids in microbiota–gut–brain cross-talk with a focus on amyotrophic lateral sclerosis: A systematic review. Int. J. Mol. Sci. 2023 24 20 15094 10.3390/ijms242015094 37894774
    [Google Scholar]
  90. Faraji N. Payami B. Ebadpour N. Gorji A. Vagus nerve stimulation and gut microbiota interactions: A novel therapeutic avenue for neuropsychiatric disorders. Neurosci. Biobehav. Rev. 2025 169 105990 10.1016/j.neubiorev.2024.105990 39716559
    [Google Scholar]
  91. Mirzaei R. Bouzari B. Hosseini-Fard S.R. Mazaheri M. Ahmadyousefi Y. Abdi M. Jalalifar S. Karimitabar Z. Teimoori A. Keyvani H. Zamani F. Yousefimashouf R. Karampoor S. Role of microbiota-derived short-chain fatty acids in nervous system disorders. Biomed. Pharmacother. 2021 139 111661 10.1016/j.biopha.2021.111661 34243604
    [Google Scholar]
  92. Barandouzi Z.A. Lee J. del Carmen Rosas M. Chen J. Henderson W.A. Starkweather A.R. Cong X.S. Associations of neurotransmitters and the gut microbiome with emotional distress in mixed type of irritable bowel syndrome. Sci. Rep. 2022 12 1 1648 10.1038/s41598‑022‑05756‑0 35102266
    [Google Scholar]
  93. Cao J. Liu Q. Hao H. Bu Y. Tian X. Wang T. Yi H. Lactobacillus paracasei X11 ameliorates hyperuricemia and modulates gut microbiota in mice. Front. Immunol. 2022 13 940228 10.3389/fimmu.2022.940228 35874662
    [Google Scholar]
  94. Nian F. Wu L. Xia Q. Tian P. Ding C. Lu X. Akkermansia muciniphila and Bifidobacterium bifidum prevent NAFLD by regulating FXR expression and gut microbiota. J. Clin. Transl. Hepatol. 2023 000 000 000 10.14218/JCTH.2022.00415 37408808
    [Google Scholar]
  95. Azad M.A.K. Sarker M. Li T. Yin J. Probiotic species in the modulation of gut microbiota: An overview. BioMed Res. Int. 2018 2018 1 1 8 10.1155/2018/9478630 29854813
    [Google Scholar]
  96. Lew L.C. Hor Y.Y. Yusoff N.A.A. Choi S.B. Yusoff M.S.B. Roslan N.S. Ahmad A. Mohammad J.A.M. Abdullah M.F.I.L. Zakaria N. Wahid N. Sun Z. Kwok L.Y. Zhang H. Liong M.T. 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 2064 10.1016/j.clnu.2018.09.010 30266270
    [Google Scholar]
  97. Schaub A.C. Schneider E. Vazquez-Castellanos J.F. Schweinfurth N. Kettelhack C. Doll J.P.K. Yamanbaeva G. Mählmann L. Brand S. Beglinger C. Borgwardt S. Raes J. Schmidt A. Lang U.E. Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: A randomized controlled trial. Transl. Psychiatry 2022 12 1 227 10.1038/s41398‑022‑01977‑z 35654766
    [Google Scholar]
  98. Kaur S. Sharma P. Mayer M.J. Neuert S. Narbad A. Kaur S. Beneficial effects of GABA-producing potential probiotic Limosilactobacillus fermentum L18 of human origin on intestinal permeability and human gut microbiota. Microb. Cell Fact. 2023 22 1 256 10.1186/s12934‑023‑02264‑2 38087304
    [Google Scholar]
  99. Potter K. Gayle E.J. Deb S. Effect of gut microbiome on serotonin metabolism: A personalized treatment approach. Naunyn Schmiedebergs Arch. Pharmacol. 2024 397 5 2589 2602 10.1007/s00210‑023‑02762‑5 37922012
    [Google Scholar]
  100. Sánchez B. Delgado S. Blanco-Míguez A. Lourenço A. Gueimonde M. Margolles A. Probiotics, gut microbiota, and their influence on host health and disease. Mol. Nutr. Food Res. 2017 61 1 1600240 10.1002/mnfr.201600240 27500859
    [Google Scholar]
  101. Park M.R. Shin M. Mun D. Jeong S.Y. Jeong D.Y. Song M. Ko G. Unno T. Kim Y. Oh S. Probiotic Lactobacillus fermentum strain JDFM216 improves cognitive behavior and modulates immune response with gut microbiota. Sci. Rep. 2020 10 1 21701 10.1038/s41598‑020‑77587‑w 33303803
    [Google Scholar]
  102. Huang E. Kang S. Park H. Park S. Ji Y. Holzapfel W.H. Differences in anxiety levels of various murine models in relation to the gut microbiota composition. Biomedicines 2018 6 4 113 10.3390/biomedicines6040113 30518033
    [Google Scholar]
  103. Davani-Davari D. Negahdaripour M. Karimzadeh I. Seifan M. Mohkam M. Masoumi S. Berenjian A. Ghasemi Y. Prebiotics: definition, types, sources, mechanisms, and clinical applications. Foods 2019 8 3 92 10.3390/foods8030092 30857316
    [Google Scholar]
  104. Li H.Y. Zhou D.D. Gan R.Y. Huang S.Y. Zhao C.N. Shang A. Xu X.Y. Li H.B. Effects and mechanisms of probiotics, prebiotics, synbiotics, and postbiotics on metabolic diseases targeting gut microbiota: A narrative review. Nutrients 2021 13 9 3211 10.3390/nu13093211 34579087
    [Google Scholar]
  105. Dou Y. Yu X. Luo Y. Chen B. Ma D. Zhu J. Effect of fructooligosaccharides supplementation on the gut microbiota in human: A systematic review and meta-analysis. Nutrients 2022 14 16 3298 10.3390/nu14163298 36014803
    [Google Scholar]
  106. Silva R.S. Mendonça I.P. Paiva I.H.R. Souza J.R.B. Peixoto C.A. Fructooligosaccharides and galactooligosaccharides improve hepatic steatosis via gut microbiota-brain axis modulation. Int. J. Food Sci. Nutr. 2023 74 7 760 780 10.1080/09637486.2023.2262779 37771001
    [Google Scholar]
  107. Simpson H.L. Campbell B.J. Review article: Dietary fibre-microbiota interactions. Aliment. Pharmacol. Ther. 2015 42 2 158 179 10.1111/apt.13248 26011307
    [Google Scholar]
  108. Gupta S. Dinesh S. Sharma S. Bridging the mind and gut: Uncovering the intricacies of neurotransmitters, neuropeptides, and their influence on neuropsychiatric disorders. Cent. Nerv. Syst. Agents Med. Chem. 2024 24 1 2 21 10.2174/0118715249271548231115071021 38265387
    [Google Scholar]
  109. Parker A. Fonseca S. Carding S.R. Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health. Gut Microbes 2020 11 2 135 157 10.1080/19490976.2019.1638722 31368397
    [Google Scholar]
  110. Burokas A. Arboleya S. Moloney R.D. Peterson V.L. Murphy K. Clarke G. Stanton C. Dinan T.G. Cryan J.F. Targeting the microbiota-gut-brain axis: Prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol. Psychiatry 2017 82 7 472 487 10.1016/j.biopsych.2016.12.031 28242013
    [Google Scholar]
  111. Liu Q. Xi Y. Wang Q. Liu J. Li P. Meng X. Liu K. Chen W. Liu X. Liu Z. Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer’s disease mouse model via regulating the gut microbiota-brain axis. Brain Behav. Immun. 2021 95 330 343 10.1016/j.bbi.2021.04.005 33839232
    [Google Scholar]
  112. Aslam H. Lotfaliany M. So D. Berding K. Berk M. Rocks T. Hockey M. Jacka F.N. Marx W. Cryan J.F. Staudacher H.M. Fiber intake and fiber intervention in depression and anxiety: A systematic review and meta-analysis of observational studies and randomized controlled trials. Nutr. Rev. 2024 82 12 1678 1695 10.1093/nutrit/nuad143 38007616
    [Google Scholar]
  113. Cauli O. New effects of prebiotics, probiotics, and symbiotics. Curr. Clin. Pharmacol. 2020 15 3 172 173 10.2174/157488471503201110093435 33327908
    [Google Scholar]
  114. Bistas K.G. Tabet J.P. The benefits of prebiotics and probiotics on mental health. Cureus 2023 15 8 e43217 10.7759/cureus.43217 37692658
    [Google Scholar]
  115. Antony M.A. Chowdhury A. Edem D. Raj R. Nain P. Joglekar M. Verma V. Kant R. Gut microbiome supplementation as therapy for metabolic syndrome. World J. Diabetes 2023 14 10 1502 1513 10.4239/wjd.v14.i10.1502 37970133
    [Google Scholar]
  116. Colletti A. Pellizzato M. Cicero A.F. The possible role of probiotic supplementation in inflammation: A narrative review. Microorganisms 2023 11 9 2160 10.3390/microorganisms11092160 37764004
    [Google Scholar]
  117. Łagowska K. Bajerska J. Kamiński S. Del Bo’ C. Effects of probiotics supplementation on gastrointestinal symptoms in athletes: A systematic review of randomized controlled trials. Nutrients 2022 14 13 2645 10.3390/nu14132645 35807826
    [Google Scholar]
  118. Freijy T.M. Cribb L. Oliver G. Metri N.J. Opie R.S. Jacka F.N. Hawrelak J.A. Rucklidge J.J. Ng C.H. Sarris J. Effects of a high-prebiotic diet versus probiotic supplements versus synbiotics on adult mental health: The “Gut Feelings” randomised controlled trial. Front. Neurosci. 2023 16 1097278 10.3389/fnins.2022.1097278 36815026
    [Google Scholar]
  119. Hamamah S. Amin A. Al-Kassir A.L. Chuang J. Covasa M. Dietary fat modulation of gut microbiota and impact on regulatory pathways controlling food intake. Nutrients 2023 15 15 3365 10.3390/nu15153365 37571301
    [Google Scholar]
  120. Álvarez-Herms J. Odriozola A. Microbiome and physical activity. Adv. Genet. 2024 111 409 450 10.1016/bs.adgen.2024.01.002 38908903
    [Google Scholar]
  121. Meyers G.R. Samouda H. Bohn T. Short chain fatty acid metabolism in relation to gut microbiota and genetic variability. Nutrients 2022 14 24 5361 10.3390/nu14245361 36558520
    [Google Scholar]
  122. Porcari S. Benech N. Valles-Colomer M. Segata N. Gasbarrini A. Cammarota G. Sokol H. Ianiro G. Key determinants of success in fecal microbiota transplantation: From microbiome to clinic. Cell Host Microbe 2023 31 5 712 733 10.1016/j.chom.2023.03.020 37167953
    [Google Scholar]
  123. Wu R. Xiong R. Li Y. Chen J. Yan R. Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation. J. Autoimmun. 2023 141 103062 10.1016/j.jaut.2023.103062 37246133
    [Google Scholar]
  124. Chinna Meyyappan A. Forth E. Wallace C.J.K. Milev R. Effect of fecal microbiota transplant on symptoms of psychiatric disorders: A systematic review. BMC Psychiatry 2020 20 1 299 10.1186/s12888‑020‑02654‑5 32539741
    [Google Scholar]
  125. Lu Y. Yuan X. Wang M. He Z. Li H. Wang J. Li Q. Gut microbiota influence immunotherapy responses: Mechanisms and therapeutic strategies. J. Hematol. Oncol. 2022 15 1 47 10.1186/s13045‑022‑01273‑9 35488243
    [Google Scholar]
  126. Niccolai E. Martinelli I. Quaranta G. Nannini G. Zucchi E. De Maio F. Gianferrari G. Bibbò S. Cammarota G. Mandrioli J. Fecal microbiota transplantation in amyotrophic lateral sclerosis: Clinical protocol and evaluation of microbiota immunity axis. Methods Mol. Biol. 2024 2761 373 396 10.1007/978‑1‑0716‑3662‑6_27
    [Google Scholar]
  127. Chen R. Xu Y. Wu P. Zhou H. Lasanajak Y. Fang Y. Tang L. Ye L. Li X. Cai Z. Zhao J. Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota. Pharmacol. Res. 2019 148 104403 10.1016/j.phrs.2019.104403 31425750
    [Google Scholar]
  128. Settanni C.R. Ianiro G. Bibbò S. Cammarota G. Gasbarrini A. Gut microbiota alteration and modulation in psychiatric disorders: Current evidence on fecal microbiota transplantation. Prog. Neuropsychopharmacol. Biol. Psychiatry 2021 109 110258 10.1016/j.pnpbp.2021.110258 33497754
    [Google Scholar]
  129. Purdel C. Margină D. Adam-Dima I. Ungurianu A. The beneficial effects of dietary interventions on gut microbiota—An up-to-date critical review and future perspectives. Nutrients 2023 15 23 5005 10.3390/nu15235005 38068863
    [Google Scholar]
  130. Beam A. Clinger E. Hao L. Effect of diet and dietary components on the composition of the gut microbiota. Nutrients 2021 13 8 2795 10.3390/nu13082795 34444955
    [Google Scholar]
  131. Sergeev I.N. Aljutaily T. Walton G. Huarte E. Effects of synbiotic supplement on human gut microbiota, body composition and weight loss in obesity. Nutrients 2020 12 1 222 10.3390/nu12010222 31952249
    [Google Scholar]
  132. Wolter M. Grant E.T. Boudaud M. Steimle A. Pereira G.V. Martens E.C. Desai M.S. Leveraging diet to engineer the gut microbiome. Nat. Rev. Gastroenterol. Hepatol. 2021 18 12 885 902 10.1038/s41575‑021‑00512‑7 34580480
    [Google Scholar]
  133. Zhang C. Yin A. Li H. Wang R. Wu G. Shen J. Zhang M. Wang L. Hou Y. Ouyang H. Zhang Y. Zheng Y. Wang J. Lv X. Wang Y. Zhang F. Zeng B. Li W. Yan F. Zhao Y. Pang X. Zhang X. Fu H. Chen F. Zhao N. Hamaker B.R. Bridgewater L.C. Weinkove D. Clement K. Dore J. Holmes E. Xiao H. Zhao G. Yang S. Bork P. Nicholson J.K. Wei H. Tang H. Zhang X. Zhao L. Dietary modulation of gut microbiota contributes to alleviation of both genetic and simple obesity in children. EBioMedicine 2015 2 8 968 984 10.1016/j.ebiom.2015.07.007 26425705
    [Google Scholar]
  134. Basso M. Zorzan I. Johnstone N. Barberis M. Cohen Kadosh K. Diet quality and anxiety: A critical overview with focus on the gut microbiome. Front. Nutr. 2024 11 1346483 10.3389/fnut.2024.1346483 38812941
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673356125250409182218
Loading
/content/journals/cmc/10.2174/0109298673356125250409182218
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test