Skip to content
2000
Volume 32, Issue 37
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

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.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673356125250409182218
2025-04-25
2025-11-01

  • From This Site

    /content/journals/cmc/10.2174/0109298673356125250409182218
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AntosZ. ZackiewiczK. TomaszekN. ModzelewskiS. WaszkiewiczN. Beyond pharmacology: A narrative review of alternative therapies for anxiety disorders.Diseases202412921610.3390/diseases1209021639329885
     [Google Scholar]
  2. TeessonM. MitchellP.B. DeadyM. MemedovicS. SladeT. BaillieA. 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. Psychiatry2011451193994610.3109/00048674.2011.61459021967412
     [Google Scholar]
  3. PathakY.V. PathakS. StoughC. Anxiety, gut microbiome, and nutraceuticals: Recent trends and clinical evidence.CRC PressBoca Raton202310.1201/9781003333821
     [Google Scholar]
  4. GenerosoJ.S. GiridharanV.V. LeeJ. MacedoD. BarichelloT. The role of the microbiota-gut-brain axis in neuropsychiatric disorders.Br. J. Psychiatry202143329330510.1590/1516‑4446‑2020‑098732667590
     [Google Scholar]
  5. RutschA. KantsjöJ.B. RonchiF. The gut-brain axis: How microbiota and host inflammasome influence brain physiology and pathology.Front. Immunol.20201160417910.3389/fimmu.2020.60417933362788
     [Google Scholar]
  6. CurtiC.F. BossolaniJ.A. CamargoR.A. CarameloA.A.F. SilvaM.G.L. FavaroM.E.F. SoncinL.V. IsmaelL. CostaM.C.S. MarimA.G. DolciC.E.M. BossoH. The gut-brain axis: Exploring the role of microbiota in depression and anxiety disorder.Int. J. Health Sci.202442621310.22533/at.ed.1594262418038
     [Google Scholar]
  7. SocałaK. DoboszewskaU. SzopaA. SerefkoA. WłodarczykM. ZielińskaA. PoleszakE. FichnaJ. WlaźP. The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders.Pharmacol. Res.202117210584010.1016/j.phrs.2021.10584034450312
     [Google Scholar]
  8. MontagnaniM. BottalicoL. PotenzaM.A. CharitosI.A. TopiS. ColellaM. SantacroceL. The crosstalk between gut microbiota and nervous system: A bidirectional interaction between microorganisms and metabolome.Int. J. Mol. Sci.202324121032210.3390/ijms24121032237373470
     [Google Scholar]
  9. WangH. ZhaoT. LiuZ. Danzengquzhen Cisangzhuoma MaJ. LiX. HuangX. LiB. The neuromodulatory effects of flavonoids and gut microbiota through the gut-brain axis.Front. Cell. Infect. Microbiol.202313119764610.3389/fcimb.2023.119764637424784
     [Google Scholar]
  10. MediavillaC. Bidirectional gut-brain communication: A role for orexin-A.Neurochem. Int.202014110488210.1016/j.neuint.2020.10488233068686
     [Google Scholar]
  11. PetraA.I. PanagiotidouS. HatziagelakiE. StewartJ.M. ContiP. TheoharidesT.C. Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation.Clin. Ther.201537598499510.1016/j.clinthera.2015.04.00226046241
     [Google Scholar]
  12. ThionM.S. LowD. SilvinA. ChenJ. GriselP. Schulte-SchreppingJ. BlecherR. UlasT. SquarzoniP. HoeffelG. Microbiome influences prenatal and adult microglia in a sex-specific manner.Cell2018172350051610.1016/j.cell.2017.11.04229275859
     [Google Scholar]
  13. ErnyD. Hrabě de AngelisA.L. JaitinD. WieghoferP. StaszewskiO. DavidE. Keren-ShaulH. MahlakoivT. JakobshagenK. BuchT. SchwierzeckV. UtermöhlenO. ChunE. GarrettW.S. McCoyK.D. DiefenbachA. StaeheliP. StecherB. AmitI. PrinzM. Host microbiota constantly control maturation and function of microglia in the CNS.Nat. Neurosci.201518796597710.1038/nn.403026030851
     [Google Scholar]
  14. SperandioV. TorresA.G. JarvisB. NataroJ.P. KaperJ.B. Bacteria–host communication: The language of hormones.Proc. Natl. Acad. Sci. USA2003100158951895610.1073/pnas.153710010012847292
     [Google Scholar]
  15. YeoS. ParkH. JiY. ParkS. YangJ. LeeJ. MatharaJ.M. ShinH. HolzapfelW. Influence of gastrointestinal stress on autoinducer-2 activity of two Lactobacillus species.FEMS Microbiol. Ecol.2015917fiv06510.1093/femsec/fiv06526092949
     [Google Scholar]
  16. SacoorC. MaruggJ.D. LimaN.R. EmpadinhasN. MontezinhoL. Gut-brain axis impact on canine anxiety disorders: New challenges for behavioral veterinary medicine.Vet. Med. Int.202420241285675910.1155/2024/285675938292207
     [Google Scholar]
  17. Malan-MullerS. Valles-ColomerM. RaesJ. LowryC.A. SeedatS. HemmingsS.M.J. The gut microbiome and mental health: Implications for anxiety-and trauma-related disorders.OMICS20182229010710.1089/omi.2017.007728767318
     [Google Scholar]
  18. LydiardR.B. The role of GABA in anxiety disorders.J. Clin. Psychiatry200364Suppl. 3212712662130
     [Google Scholar]
  19. WuJ.T. SunC.L. LaiT.T. LiouC.W. LinY.Y. XueJ.Y. WangH.W. ChaiL.M.X. LeeY.J. ChenS.L. ChangA.Y.W. HungJ.H. HsuC.C. WuW.L. Oral short-chain fatty acids administration regulates innate anxiety in adult microbiome-depleted mice.Neuropharmacology202221410914010.1016/j.neuropharm.2022.10914035613660
     [Google Scholar]
  20. YangD.F. HuangW.C. WuC.W. HuangC.Y. YangY.C.S.H. TungY.T. Acute sleep deprivation exacerbates systemic inflammation and psychiatry disorders through gut microbiota dysbiosis and disruption of circadian rhythms.Microbiol. Res.202326812729210.1016/j.micres.2022.12729236608535
     [Google Scholar]
  21. BravoJ.A. Julio-PieperM. ForsytheP. KunzeW. DinanT.G. BienenstockJ. CryanJ.F. Communication between gastrointestinal bacteria and the nervous system.Curr. Opin. Pharmacol.201212666767210.1016/j.coph.2012.09.01023041079
     [Google Scholar]
  22. ChakrabartiA. GeurtsL. HoylesL. IozzoP. KraneveldA.D. La FataG. MianiM. PattersonE. PotB. ShorttC. VauzourD. 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.20227928010.1007/s00018‑021‑04060‑w35044528
     [Google Scholar]
  23. AnandN. GorantlaV.R. ChidambaramS.B. The role of gut dysbiosis in the pathophysiology of neuropsychiatric disorders.Cells20221215410.3390/cells1201005436611848
     [Google Scholar]
  24. Milà-GuaschM. RamírezS. LlanaS.R. Fos-DomènechJ. DropmannL.M. PozoM. EyreE. Gómez-ValadésA.G. ObriA. Haddad-TóvolliR. ClaretM. Maternal emulsifier consumption programs offspring metabolic and neuropsychological health in mice.PLoS Biol.2023218e300217110.1371/journal.pbio.300217137616199
     [Google Scholar]
  25. LeighS.J. UhligF. WilmesL. Sanchez-DiazP. GheorgheC.E. GoodsonM.S. Kelley-LoughnaneN. HylandN.P. CryanJ.F. ClarkeG. The impact of acute and chronic stress on gastrointestinal physiology and function: A microbiota–gut–brain axis perspective.J. Physiol.2023601204491453810.1113/JP28195137756251
     [Google Scholar]
  26. XiaoQ. ShuR. WuC. TongY. XiongZ. ZhouJ. YuC. XieX. FuZ. Crocin-I alleviates the depression-like behaviors probably via modulating “microbiota-gut-brain” axis in mice exposed to chronic restraint stress.J. Affect. Disord.202027647648610.1016/j.jad.2020.07.04132871679
     [Google Scholar]
  27. BercikP. CollinsS.M. The effects of inflammation, infection and antibiotics on the microbiota-gut-brain axis.Adv. Exp. Med. Biol.201481727928910.1007/978‑1‑4939‑0897‑4_1324997039
     [Google Scholar]
  28. BaumelW.T. MillsJ.A. SchroederH.K. NeptuneZ. LevineA. StrawnJ.R. Gastrointestinal symptoms in pediatric patients with anxiety disorders and their relationship to selective serotonin reuptake inhibitor treatment or placebo.Child Psychiatry Hum. Dev.202311210.1007/s10578‑023‑01586‑x37659029
     [Google Scholar]
  29. BaskeM.M. TimmermanK.C. GarmoL.G. FreitasM.N. McCollumK.A. RenT.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.202435430931710.1016/j.jad.2024.03.08838499070
     [Google Scholar]
  30. AslamH. GreenJ. JackaF.N. CollierF. BerkM. PascoJ. DawsonS.L. Fermented foods, the gut and mental health: A mechanistic overview with implications for depression and anxiety.Nutr. Neurosci.202023965967110.1080/1028415X.2018.154433230415609
     [Google Scholar]
  31. WasiakJ. Gawlik-KotelnickaO. Intestinal permeability and its significance in psychiatric disorders – A narrative review and future perspectives.Behav. Brain Res.202344811445910.1016/j.bbr.2023.11445937121278
     [Google Scholar]
  32. JuruenaM.F. ErorF. CleareA.J. YoungA.H. The role of early life stress in HPA axis and anxiety.Anxiety Disorders. Advances in Experimental Medicine and Biology; Kim, Y.K., EdSpringerSingapore2020Vol. 1191141153
     [Google Scholar]
  33. YoonS. KimY.-K. The role of the oxytocin system in anxiety disorders.Adv. Exp. Med. Biol.2020119110312010.1007/978‑981‑32‑9705‑0_732002925
     [Google Scholar]
  34. FeliceD. GABAB receptors: Anxiety and mood disordersCurr. Top. Behav. Neurosci.20225224126510.1007/7854_2020_17132860591
     [Google Scholar]
  35. NikolausS. AntkeC. BeuM. MüllerH.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.201021211913910.1515/REVNEURO.2010.21.2.11920614802
     [Google Scholar]
  36. KriegerJ.P. AskerM. van der VeldenP. BörchersS. RichardJ.E. MaricI. LongoF. SinghA. de LartigueG. SkibickaK.P. Neural pathway for gut feelings: Vagal interoceptive feedback from the gastrointestinal tract is a critical modulator of anxiety-like behavior.Biol. Psychiatry202292970972110.1016/j.biopsych.2022.04.02035965105
     [Google Scholar]
  37. XiaG. HanY. MengF. HeY. SrisaiD. FariasM. DangM. PalmiterR.D. XuY. WuQ. Reciprocal control of obesity and anxiety–depressive disorder via a GABA and serotonin neural circuit.Mol. Psychiatry20212672837285310.1038/s41380‑021‑01053‑w33767348
     [Google Scholar]
  38. JindalA. MaheshR. KumarB. Anxiolytic-like effect of linezolid in experimental mouse models of anxiety.Prog. Neuropsychopharmacol. Biol. Psychiatry201340475310.1016/j.pnpbp.2012.09.00623021974
     [Google Scholar]
  39. SchmidtnerA.K. SlatteryD.A. GläsnerJ. HiergeistA. GryksaK. MalikV.A. Hellmann-RegenJ. HeuserI. BaghaiT.C. GessnerA. RupprechtR. Di BenedettoB. NeumannI.D. Minocycline alters behavior, microglia and the gut microbiome in a trait-anxiety-dependent manner.Transl. Psychiatry20199122310.1038/s41398‑019‑0556‑931519869
     [Google Scholar]
  40. GloverM.E. CohenJ.L. SingerJ.R. SabbaghM.N. RainvilleJ.R. HylandM.T. MorrowC.D. WeaverC.T. HodesG.E. KermanI.A. ClintonS.M. Examining the role of microbiota in emotional behavior: Antibiotic treatment exacerbates anxiety in high anxiety-prone male rats.Neuroscience202145917919710.1016/j.neuroscience.2021.01.03033540050
     [Google Scholar]
  41. MajidiJ. Kosari-NasabM. SalariA.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.201612011310.1016/j.brainresbull.2015.10.00926521068
     [Google Scholar]
  42. KimS.Y. WooS.Y. RazaS. HoD. JeonS.W. ChangY. RyuS. KimH.L. KimH.N. Association between gut microbiota and anxiety symptoms: A large population-based study examining sex differences.J. Affect. Disord.2023333212910.1016/j.jad.2023.04.00337031878
     [Google Scholar]
  43. NikolovaV.L. SmithM.R.B. HallL.J. CleareA.J. StoneJ.M. YoungA.H. Perturbations in gut microbiota composition in psychiatric disorders: A review and meta-analysis.JAMA Psychiatry202178121343135410.1001/jamapsychiatry.2021.257334524405
     [Google Scholar]
  44. GasmiA. BjørklundG. MujawdiyaP.K. SemenovaY. DosaA. PiscopoS. PenJ.J. BenahmedA.G. CosteaD.O. Gut microbiota in bariatric surgery.Crit. Rev. Food Sci. Nutr.202363289299931410.1080/10408398.2022.206711635531940
     [Google Scholar]
  45. BearT.L.K. DalzielJ.E. CoadJ. RoyN.C. ButtsC.A. GopalP.K. The role of the gut microbiota in dietary interventions for depression and anxiety.Adv. Nutr.202011489090710.1093/advances/nmaa01632149335
     [Google Scholar]
  46. CryanJ.F. DinanT.G. Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour.Nat. Rev. Neurosci.2012131070171210.1038/nrn334622968153
     [Google Scholar]
  47. AnsariF. PourjafarH. TabriziA. HomayouniA. The effects of probiotics and prebiotics on mental disorders: A review on depression, anxiety, Alzheimer, and autism spectrum disorders.Curr. Pharm. Biotechnol.202021755556510.2174/138920102166620010711381231914909
     [Google Scholar]
  48. LiuR.T. WalshR.F.L. SheehanA.E. Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials.Neurosci. Biobehav. Rev.2019102132310.1016/j.neubiorev.2019.03.02331004628
     [Google Scholar]
  49. SimpsonC.A. Diaz-ArtecheC. ElibyD. SchwartzO.S. SimmonsJ.G. CowanC.S.M. The gut microbiota in anxiety and depression – A systematic review.Clin. Psychol. Rev.20218310194310.1016/j.cpr.2020.10194333271426
     [Google Scholar]
  50. WileyN.C. DinanT.G. RossR.P. StantonC. ClarkeG. CryanJ.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.20179573225324628727115
     [Google Scholar]
  51. KutiD. WinklerZ. HorváthK. JuhászB. PaholcsekM. StágelA. GulyásG. CzeglédiL. FerencziS. KovácsK.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.20208421822810.1016/j.bbi.2019.12.00431821847
     [Google Scholar]
  52. CaniP.D. BibiloniR. KnaufC. WagetA. NeyrinckA.M. DelzenneN.M. BurcelinR. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice.Diabetes20085761470148110.2337/db07‑140318305141
     [Google Scholar]
  53. On WahD.T. KavaliersM. BishnoiI.R. OssenkoppK.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.201936031232210.1016/j.bbr.2018.12.00330521932
     [Google Scholar]
  54. HsiaoE.Y. McBrideS.W. HsienS. SharonG. HydeE.R. McCueT. CodelliJ.A. ChowJ. ReismanS.E. PetrosinoJ.F. The microbiota modulates gut physiology and behavioral abnormalities associated with autism.Cell20131557145110.1016/j.cell.2013.11.02424315484
     [Google Scholar]
  55. BernsteinC.N. The brain-gut axis and stress in inflammatory bowel disease.Gastroenterol. Clin. North Am.201746483984610.1016/j.gtc.2017.08.00629173525
     [Google Scholar]
  56. El-HakimY. BakeS. ManiK.K. SohrabjiF. Impact of intestinal disorders on central and peripheral nervous system diseases.Neurobiol. Dis.202216510562710.1016/j.nbd.2022.10562735032636
     [Google Scholar]
  57. StillingR.M. RyanF.J. HobanA.E. ShanahanF. ClarkeG. ClaessonM.J. DinanT.G. CryanJ.F. Microbes & neurodevelopment – Absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala.Brain Behav. Immun.20155020922010.1016/j.bbi.2015.07.00926184083
     [Google Scholar]
  58. BearT. DalzielJ. CoadJ. RoyN. ButtsC. GopalP. The microbiome-gut-brain axis and resilience to developing anxiety or depression under stress.Microorganisms20219472310.3390/microorganisms904072333807290
     [Google Scholar]
  59. FieldsC.T. ChassaingB. Castillo-RuizA. OsanR. GewirtzA.T. de VriesG.J. Effects of gut-derived endotoxin on anxiety-like and repetitive behaviors in male and female mice.Biol. Sex Differ.201891710.1186/s13293‑018‑0166‑x29351816
     [Google Scholar]
  60. ŁośK. WaszkiewiczN. Biological markers in anxiety disorders.J. Clin. Med.2021108174410.3390/jcm1008174433920547
     [Google Scholar]
  61. GiollabhuiN.M. SlaneyC. HemaniG. FoleyE. van der MostP. NolteI. SniederH. SmithG.D. KhandakerG. HartmanC. Role of inflammation in depressive and anxiety disorders, affect, and cognition: Genetic and non-genetic findings in the lifelines cohort study.medRxiv2024
     [Google Scholar]
  62. van EedenW.A. El FilaliE. van HemertA.M. CarlierI.V.E. PenninxB.W.J.H. LamersF. SchoeversR. GiltayE.J. Basal and LPS-stimulated inflammatory markers and the course of anxiety symptoms.Brain Behav. Immun.20219837838710.1016/j.bbi.2021.09.00134509625
     [Google Scholar]
  63. FengX.Z. LiZ. LiZ.Y. WangK. TanX. ZhaoY.Y. MiW.F. ZhuW.L. BaoY.P. LuL. LiS.X. Effectiveness and safety of second-generation antipsychotics for psychiatric disorders apart from schizophrenia: A systematic review and meta-analysis.Psychiatry Res.202433211563710.1016/j.psychres.2023.11563738150810
     [Google Scholar]
  64. ThronsonL.R. PagalilauanG.L. Psychopharmacology.Med. Clin. North Am.201498592795810.1016/j.mcna.2014.06.00125134867
     [Google Scholar]
  65. McGuinnessA.J. DavisJ.A. DawsonS.L. LoughmanA. CollierF. O’HelyM. SimpsonC.A. GreenJ. MarxW. HairC. GuestG. MohebbiM. BerkM. StupartD. WattersD. JackaF.N. A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia.Mol. Psychiatry20222741920193510.1038/s41380‑022‑01456‑335194166
     [Google Scholar]
  66. ZengC. YangP. CaoT. GuY. LiN. ZhangB. XuP. LiuY. LuoZ. CaiH. Gut microbiota: An intermediary between metabolic syndrome and cognitive deficits in schizophrenia.Prog. Neuropsychopharmacol. Biol. Psychiatry202110611009710.1016/j.pnpbp.2020.11009732916223
     [Google Scholar]
  67. DiasM.F. NogueiraY.J.A. Romano-SilvaM.A. Marques de MirandaD. Effects of antipsychotics on the gastrointestinal microbiota: A systematic review.Psychiatry Res.202433611591410.1016/j.psychres.2024.11591438663221
     [Google Scholar]
  68. TomizawaY. KurokawaS. IshiiD. MiyahoK. IshiiC. SanadaK. FukudaS. MimuraM. KishimotoT. Effects of psychotropics on the microbiome in patients with depression and anxiety: Considerations in a naturalistic clinical setting.Int. J. Neuropsychopharmacol.20212429710710.1093/ijnp/pyaa07032975292
     [Google Scholar]
  69. ZhangY. FanQ. HouY. ZhangX. YinZ. CaiX. WeiW. WangJ. HeD. WangG. YuanY. HaoH. ZhengX. Bacteroides species differentially modulate depression-like behavior via gut-brain metabolic signaling.Brain Behav. Immun.2022102112210.1016/j.bbi.2022.02.00735143877
     [Google Scholar]
  70. DurantiS. RuizL. LugliG.A. TamesH. MilaniC. MancabelliL. MancinoW. LonghiG. CarnevaliL. SgoifoA. MargollesA. VenturaM. Ruas-MadiedoP. TurroniF. Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA.Sci. Rep.20201011411210.1038/s41598‑020‑70986‑z32839473
     [Google Scholar]
  71. ZhuR. FangY. LiH. LiuY. WeiJ. ZhangS. WangL. FanR. WangL. LiS. ChenT. 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.202314115813710.3389/fimmu.2023.115813737033942
     [Google Scholar]
  72. LiuP. LiuZ. WangJ. WangJ. GaoM. ZhangY. YangC. ZhangA. LiG. LiX. LiuS. LiuL. SunN. ZhangK. Immunoregulatory role of the gut microbiota in inflammatory depression.Nat. Commun.2024151300310.1038/s41467‑024‑47273‑w38589368
     [Google Scholar]
  73. HuangF. WuX. Brain neurotransmitter modulation by gut microbiota in anxiety and depression.Front. Cell Dev. Biol.2021964910310.3389/fcell.2021.64910333777957
     [Google Scholar]
  74. TakayanagiY. OnakaT. Roles of oxytocin in stress responses, allostasis and resilience.Int. J. Mol. Sci.202123115010.3390/ijms2301015035008574
     [Google Scholar]
  75. AllenM.J. GABA ReceptorStatPearlsTreasure Island, FL Statpearls Publishing2025
     [Google Scholar]
  76. Dresp-LangleyB. From reward to anhedonia-dopamine function in the global mental health context.Biomedicines2023119246910.3390/biomedicines1109246937760910
     [Google Scholar]
  77. AlbertP.R. Vahid-AnsariF. LuckhartC. Serotonin-prefrontal cortical circuitry in anxiety and depression phenotypes: Pivotal role of pre- and post-synaptic 5-HT1A receptor expression.Front. Behav. Neurosci.2014819910.3389/fnbeh.2014.0019924936175
     [Google Scholar]
  78. LiuG. ChongH.X. ChungF.Y.L. LiY. LiongM.T. Lactobacillus plantarum DR7 modulated bowel movement and gut microbiota associated with dopamine and serotonin pathways in stressed adults.Int. J. Mol. Sci.20202113460810.3390/ijms2113460832610495
     [Google Scholar]
  79. BhatiaN.Y. JalgaonkarM.P. HargudeA.B. SherjeA.P. OzaM.J. DoshiG.M. Gut-brain axis and neurological disorders-how microbiomes affect our mental health.CNS Neurol. Disord. Drug Targets20232271008103010.2174/187152732166622082217203936017855
     [Google Scholar]
  80. O’MahonyS.M. ClarkeG. BorreY.E. DinanT.G. CryanJ.F. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis.Behav. Brain Res.2015277324810.1016/j.bbr.2014.07.02725078296
     [Google Scholar]
  81. MhannaA. MartiniN. HmaydooshG. HamwiG. JarjanaziM. ZaifahG. KazzazoR. Haji MohamadA. AlshehabiZ. The correlation between gut microbiota and both neurotransmitters and mental disorders: A narrative review.Medicine20241035e3711410.1097/MD.000000000003711438306525
     [Google Scholar]
  82. StrandwitzP. Neurotransmitter modulation by the gut microbiota.Brain Res.20181693Pt B12813310.1016/j.brainres.2018.03.01529903615
     [Google Scholar]
  83. ZanoliL. TuttolomondoA. InserraG. CappelloM. GranataA. MalatinoL. CastellinoP. Anxiety, depression, chronic inflammation and aortic stiffness in Crohn’s disease: The brain--Gut--vascular axis.J. Hypertens.202038102008201710.1097/HJH.000000000000251732890277
     [Google Scholar]
  84. SkowrońskaA. Gawlik-KotelnickaO. MargulskaA. StrzeleckiD. 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.Metabolites202313218210.3390/metabo1302018236837799
     [Google Scholar]
  85. ChengJ. HuH. JuY. LiuJ. WangM. LiuB. ZhangY. Gut microbiota-derived short-chain fatty acids and depression: Deep insight into biological mechanisms and potential applications.Gen. Psychiatr.2024371e10137410.1136/gpsych‑2023‑10137438390241
     [Google Scholar]
  86. PattersonT.T. GrandhiR. Gut microbiota and neurologic diseases and injuries.Adv. Exp. Med. Biol.20201238739110.1007/978‑981‑15‑2385‑4_632323181
     [Google Scholar]
  87. StevensB.R. GoelR. SeungbumK. RichardsE.M. HolbertR.C. PepineC.J. RaizadaM.K. Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression.Gut20186781555.2155710.1136/gutjnl‑2017‑31475928814485
     [Google Scholar]
  88. ZhangK. ChenL. YangJ. LiuJ. LiJ. LiuY. LiX. ChenL. HsuC. ZengJ. XieX. WangQ. 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. B202313124801482210.1016/j.apsb.2023.09.01038045052
     [Google Scholar]
  89. MoțățăianuA. ȘerbanG. AndoneS. 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.202324201509410.3390/ijms24201509437894774
     [Google Scholar]
  90. FarajiN. PayamiB. EbadpourN. GorjiA. Vagus nerve stimulation and gut microbiota interactions: A novel therapeutic avenue for neuropsychiatric disorders.Neurosci. Biobehav. Rev.202516910599010.1016/j.neubiorev.2024.10599039716559
     [Google Scholar]
  91. MirzaeiR. BouzariB. Hosseini-FardS.R. MazaheriM. AhmadyousefiY. AbdiM. JalalifarS. KarimitabarZ. TeimooriA. KeyvaniH. ZamaniF. YousefimashoufR. KarampoorS. Role of microbiota-derived short-chain fatty acids in nervous system disorders.Biomed. Pharmacother.202113911166110.1016/j.biopha.2021.11166134243604
     [Google Scholar]
  92. BarandouziZ.A. LeeJ. del Carmen RosasM. ChenJ. HendersonW.A. StarkweatherA.R. CongX.S. Associations of neurotransmitters and the gut microbiome with emotional distress in mixed type of irritable bowel syndrome.Sci. Rep.2022121164810.1038/s41598‑022‑05756‑035102266
     [Google Scholar]
  93. CaoJ. LiuQ. HaoH. BuY. TianX. WangT. YiH. Lactobacillus paracasei X11 ameliorates hyperuricemia and modulates gut microbiota in mice.Front. Immunol.20221394022810.3389/fimmu.2022.94022835874662
     [Google Scholar]
  94. NianF. WuL. XiaQ. TianP. DingC. LuX. Akkermansia muciniphila and Bifidobacterium bifidum prevent NAFLD by regulating FXR expression and gut microbiota.J. Clin. Transl. Hepatol.202300000000010.14218/JCTH.2022.0041537408808
     [Google Scholar]
  95. AzadM.A.K. SarkerM. LiT. YinJ. Probiotic species in the modulation of gut microbiota: An overview.BioMed Res. Int.2018201811810.1155/2018/947863029854813
     [Google Scholar]
  96. LewL.C. HorY.Y. YusoffN.A.A. ChoiS.B. YusoffM.S.B. RoslanN.S. AhmadA. MohammadJ.A.M. AbdullahM.F.I.L. ZakariaN. WahidN. SunZ. KwokL.Y. ZhangH. LiongM.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.20193852053206410.1016/j.clnu.2018.09.01030266270
     [Google Scholar]
  97. SchaubA.C. SchneiderE. Vazquez-CastellanosJ.F. SchweinfurthN. KettelhackC. DollJ.P.K. YamanbaevaG. MählmannL. BrandS. BeglingerC. BorgwardtS. RaesJ. SchmidtA. LangU.E. Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: A randomized controlled trial.Transl. Psychiatry202212122710.1038/s41398‑022‑01977‑z35654766
     [Google Scholar]
  98. KaurS. SharmaP. MayerM.J. NeuertS. NarbadA. KaurS. Beneficial effects of GABA-producing potential probiotic Limosilactobacillus fermentum L18 of human origin on intestinal permeability and human gut microbiota.Microb. Cell Fact.202322125610.1186/s12934‑023‑02264‑238087304
     [Google Scholar]
  99. PotterK. GayleE.J. DebS. Effect of gut microbiome on serotonin metabolism: A personalized treatment approach.Naunyn Schmiedebergs Arch. Pharmacol.202439752589260210.1007/s00210‑023‑02762‑537922012
     [Google Scholar]
  100. SánchezB. DelgadoS. Blanco-MíguezA. LourençoA. GueimondeM. MargollesA. Probiotics, gut microbiota, and their influence on host health and disease.Mol. Nutr. Food Res.2017611160024010.1002/mnfr.20160024027500859
     [Google Scholar]
  101. ParkM.R. ShinM. MunD. JeongS.Y. JeongD.Y. SongM. KoG. UnnoT. KimY. OhS. Probiotic Lactobacillus fermentum strain JDFM216 improves cognitive behavior and modulates immune response with gut microbiota.Sci. Rep.20201012170110.1038/s41598‑020‑77587‑w33303803
     [Google Scholar]
  102. HuangE. KangS. ParkH. ParkS. JiY. HolzapfelW.H. Differences in anxiety levels of various murine models in relation to the gut microbiota composition.Biomedicines20186411310.3390/biomedicines604011330518033
     [Google Scholar]
  103. Davani-DavariD. NegahdaripourM. KarimzadehI. SeifanM. MohkamM. MasoumiS. BerenjianA. GhasemiY. Prebiotics: definition, types, sources, mechanisms, and clinical applications.Foods2019839210.3390/foods803009230857316
     [Google Scholar]
  104. LiH.Y. ZhouD.D. GanR.Y. HuangS.Y. ZhaoC.N. ShangA. XuX.Y. LiH.B. Effects and mechanisms of probiotics, prebiotics, synbiotics, and postbiotics on metabolic diseases targeting gut microbiota: A narrative review.Nutrients2021139321110.3390/nu1309321134579087
     [Google Scholar]
  105. DouY. YuX. LuoY. ChenB. MaD. ZhuJ. Effect of fructooligosaccharides supplementation on the gut microbiota in human: A systematic review and meta-analysis.Nutrients20221416329810.3390/nu1416329836014803
     [Google Scholar]
  106. SilvaR.S. MendonçaI.P. PaivaI.H.R. SouzaJ.R.B. PeixotoC.A. Fructooligosaccharides and galactooligosaccharides improve hepatic steatosis via gut microbiota-brain axis modulation.Int. J. Food Sci. Nutr.202374776078010.1080/09637486.2023.226277937771001
     [Google Scholar]
  107. SimpsonH.L. CampbellB.J. Review article: Dietary fibre-microbiota interactions.Aliment. Pharmacol. Ther.201542215817910.1111/apt.1324826011307
     [Google Scholar]
  108. GuptaS. DineshS. SharmaS. Bridging the mind and gut: Uncovering the intricacies of neurotransmitters, neuropeptides, and their influence on neuropsychiatric disorders.Cent. Nerv. Syst. Agents Med. Chem.202424122110.2174/011871524927154823111507102138265387
     [Google Scholar]
  109. ParkerA. FonsecaS. CardingS.R. Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health.Gut Microbes202011213515710.1080/19490976.2019.163872231368397
     [Google Scholar]
  110. BurokasA. ArboleyaS. MoloneyR.D. PetersonV.L. MurphyK. ClarkeG. StantonC. DinanT.G. CryanJ.F. Targeting the microbiota-gut-brain axis: Prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice.Biol. Psychiatry201782747248710.1016/j.biopsych.2016.12.03128242013
     [Google Scholar]
  111. LiuQ. XiY. WangQ. LiuJ. LiP. MengX. LiuK. ChenW. LiuX. LiuZ. 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.20219533034310.1016/j.bbi.2021.04.00533839232
     [Google Scholar]
  112. AslamH. LotfalianyM. SoD. BerdingK. BerkM. RocksT. HockeyM. JackaF.N. MarxW. CryanJ.F. StaudacherH.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.202482121678169510.1093/nutrit/nuad14338007616
     [Google Scholar]
  113. CauliO. New effects of prebiotics, probiotics, and symbiotics.Curr. Clin. Pharmacol.202015317217310.2174/15748847150320111009343533327908
     [Google Scholar]
  114. BistasK.G. TabetJ.P. The benefits of prebiotics and probiotics on mental health.Cureus2023158e4321710.7759/cureus.4321737692658
     [Google Scholar]
  115. AntonyM.A. ChowdhuryA. EdemD. RajR. NainP. JoglekarM. VermaV. KantR. Gut microbiome supplementation as therapy for metabolic syndrome.World J. Diabetes202314101502151310.4239/wjd.v14.i10.150237970133
     [Google Scholar]
  116. CollettiA. PellizzatoM. CiceroA.F. The possible role of probiotic supplementation in inflammation: A narrative review.Microorganisms2023119216010.3390/microorganisms1109216037764004
     [Google Scholar]
  117. ŁagowskaK. BajerskaJ. KamińskiS. Del Bo’C. Effects of probiotics supplementation on gastrointestinal symptoms in athletes: A systematic review of randomized controlled trials.Nutrients20221413264510.3390/nu1413264535807826
     [Google Scholar]
  118. FreijyT.M. CribbL. OliverG. MetriN.J. OpieR.S. JackaF.N. HawrelakJ.A. RucklidgeJ.J. NgC.H. SarrisJ. Effects of a high-prebiotic diet versus probiotic supplements versus synbiotics on adult mental health: The “Gut Feelings” randomised controlled trial.Front. Neurosci.202316109727810.3389/fnins.2022.109727836815026
     [Google Scholar]
  119. HamamahS. AminA. Al-KassirA.L. ChuangJ. CovasaM. Dietary fat modulation of gut microbiota and impact on regulatory pathways controlling food intake.Nutrients20231515336510.3390/nu1515336537571301
     [Google Scholar]
  120. Álvarez-HermsJ. OdriozolaA. Microbiome and physical activity.Adv. Genet.202411140945010.1016/bs.adgen.2024.01.00238908903
     [Google Scholar]
  121. MeyersG.R. SamoudaH. BohnT. Short chain fatty acid metabolism in relation to gut microbiota and genetic variability.Nutrients20221424536110.3390/nu1424536136558520
     [Google Scholar]
  122. PorcariS. BenechN. Valles-ColomerM. SegataN. GasbarriniA. CammarotaG. SokolH. IaniroG. Key determinants of success in fecal microbiota transplantation: From microbiome to clinic.Cell Host Microbe202331571273310.1016/j.chom.2023.03.02037167953
     [Google Scholar]
  123. WuR. XiongR. LiY. ChenJ. YanR. Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation.J. Autoimmun.202314110306210.1016/j.jaut.2023.10306237246133
     [Google Scholar]
  124. Chinna MeyyappanA. ForthE. WallaceC.J.K. MilevR. Effect of fecal microbiota transplant on symptoms of psychiatric disorders: A systematic review.BMC Psychiatry202020129910.1186/s12888‑020‑02654‑532539741
     [Google Scholar]
  125. LuY. YuanX. WangM. HeZ. LiH. WangJ. LiQ. Gut microbiota influence immunotherapy responses: Mechanisms and therapeutic strategies.J. Hematol. Oncol.20221514710.1186/s13045‑022‑01273‑935488243
     [Google Scholar]
  126. NiccolaiE. MartinelliI. QuarantaG. NanniniG. ZucchiE. De MaioF. GianferrariG. BibbòS. CammarotaG. MandrioliJ. Fecal microbiota transplantation in amyotrophic lateral sclerosis: Clinical protocol and evaluation of microbiota immunity axis.Methods Mol. Biol.2024276137339610.1007/978‑1‑0716‑3662‑6_27
     [Google Scholar]
  127. ChenR. XuY. WuP. ZhouH. LasanajakY. FangY. TangL. YeL. LiX. CaiZ. ZhaoJ. Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota.Pharmacol. Res.201914810440310.1016/j.phrs.2019.10440331425750
     [Google Scholar]
  128. SettanniC.R. IaniroG. BibbòS. CammarotaG. GasbarriniA. Gut microbiota alteration and modulation in psychiatric disorders: Current evidence on fecal microbiota transplantation.Prog. Neuropsychopharmacol. Biol. Psychiatry202110911025810.1016/j.pnpbp.2021.11025833497754
     [Google Scholar]
  129. PurdelC. MarginăD. Adam-DimaI. UngurianuA. The beneficial effects of dietary interventions on gut microbiota—An up-to-date critical review and future perspectives.Nutrients20231523500510.3390/nu1523500538068863
     [Google Scholar]
  130. BeamA. ClingerE. HaoL. Effect of diet and dietary components on the composition of the gut microbiota.Nutrients2021138279510.3390/nu1308279534444955
     [Google Scholar]
  131. SergeevI.N. AljutailyT. WaltonG. HuarteE. Effects of synbiotic supplement on human gut microbiota, body composition and weight loss in obesity.Nutrients202012122210.3390/nu1201022231952249
     [Google Scholar]
  132. WolterM. GrantE.T. BoudaudM. SteimleA. PereiraG.V. MartensE.C. DesaiM.S. Leveraging diet to engineer the gut microbiome.Nat. Rev. Gastroenterol. Hepatol.2021181288590210.1038/s41575‑021‑00512‑734580480
     [Google Scholar]
  133. ZhangC. YinA. LiH. WangR. WuG. ShenJ. ZhangM. WangL. HouY. OuyangH. ZhangY. ZhengY. WangJ. LvX. WangY. ZhangF. ZengB. LiW. YanF. ZhaoY. PangX. ZhangX. FuH. ChenF. ZhaoN. HamakerB.R. BridgewaterL.C. WeinkoveD. ClementK. DoreJ. HolmesE. XiaoH. ZhaoG. YangS. BorkP. NicholsonJ.K. WeiH. TangH. ZhangX. ZhaoL. Dietary modulation of gut microbiota contributes to alleviation of both genetic and simple obesity in children.EBioMedicine20152896898410.1016/j.ebiom.2015.07.00726425705
     [Google Scholar]
  134. BassoM. ZorzanI. JohnstoneN. BarberisM. Cohen KadoshK. Diet quality and anxiety: A critical overview with focus on the gut microbiome.Front. Nutr.202411134648310.3389/fnut.2024.134648338812941
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673356125250409182218
Loading
The Gut Microbiota-anxiety Connection: Evidence, Mechanisms, and Therapeutic Strategies
Curr. Med. Chem. 32, 8233 (2025); https://doi.org/10.2174/0109298673356125250409182218
/content/journals/cmc/10.2174/0109298673356125250409182218
/content/journals/cmc/10.2174/0109298673356125250409182218
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): antipsychotics; anxiety disorders; dietary interventions; dysbiosis; fecal microbiota transplantation; gut microbiota; Gut-brain axis; leaky gut; metabolic endotoxemia; prebiotics; probiotics; symbiotics

Most Cited Most Cited RSS feed

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