Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders

Overview

Journal Nutrients

Date 2021 Jul 2

PMID 34205336

Citations 219

Authors

Yijing Chen

Jinying Xu

Yu Chen

Affiliations

Soon will be listed here.

Abstract

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota-gut-brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

Citing Articles

Heterocyclic Antidepressants with Antimicrobial and Fungicide Activity.

Zolotareva D, Zazybin A, Belyankova Y, Bayazit S, Dauletbakov A, Seilkhanov T Molecules. 2025; 30(5).

PMID: 40076325 PMC: 11902072. DOI: 10.3390/molecules30051102.

Modulatory effects of Kratom extract on the gut microbiota of rats: implications for health.

Thongsepee N, Amonyingcharoen S, Chamod P, Himakhun W, Sangpairoj K, Martviset P BMC Complement Med Ther. 2025; 25(1):85.

PMID: 40016684 PMC: 11866890. DOI: 10.1186/s12906-025-04836-8.

Age, sex, and mitochondrial-haplotype influence gut microbiome composition and metabolites in a genetically diverse rat model.

Nguyen H, Cabello E, Dyer D, Fender C, Garcia-Jaramillo M, Hord N Aging (Albany NY). 2025; 17(2):524-549.

PMID: 40015964 PMC: 11892925. DOI: 10.18632/aging.206211.

Gut microbial dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia.

Chen A, Teng C, Wei J, Wu X, Zhang H, Chen P Gut Microbes. 2025; 17(1):2471015.

PMID: 40008452 PMC: 11866968. DOI: 10.1080/19490976.2025.2471015.

Mental Health Disorders Due to Gut Microbiome Alteration and NLRP3 Inflammasome Activation After Spinal Cord Injury: Molecular Mechanisms, Promising Treatments, and Aids from Artificial Intelligence.

Kalaga P, Ray S Brain Sci. 2025; 15(2).

PMID: 40002529 PMC: 11852823. DOI: 10.3390/brainsci15020197.

References

Maini Rekdal V, Bess E, Bisanz J, Turnbaugh P, Balskus E . Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science. 2019; 364(6445). PMC: 7745125. DOI: 10.1126/science.aau6323. View

Romano S, Savva G, Bedarf J, Charles I, Hildebrand F, Narbad A . Meta-analysis of the Parkinson's disease gut microbiome suggests alterations linked to intestinal inflammation. NPJ Parkinsons Dis. 2021; 7(1):27. PMC: 7946946. DOI: 10.1038/s41531-021-00156-z. View

Kuai X, Yao X, Xu L, Zhou Y, Zhang L, Liu Y . Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation. Microb Cell Fact. 2021; 20(1):98. PMC: 8120701. DOI: 10.1186/s12934-021-01589-0. View

Vogt N, Kerby R, Dill-McFarland K, Harding S, Merluzzi A, Johnson S . Gut microbiome alterations in Alzheimer's disease. Sci Rep. 2017; 7(1):13537. PMC: 5648830. DOI: 10.1038/s41598-017-13601-y. View

Zaragoza R . Transport of Amino Acids Across the Blood-Brain Barrier. Front Physiol. 2020; 11:973. PMC: 7538855. DOI: 10.3389/fphys.2020.00973. View

Vaughan C, Aherne A, Lane E, Power O, Carey R, OConnell D . Identification and regional distribution of the dopamine D(1A) receptor in the gastrointestinal tract. Am J Physiol Regul Integr Comp Physiol. 2000; 279(2):R599-609. DOI: 10.1152/ajpregu.2000.279.2.R599. View

Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson E . Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018; 555(7698):623-628. PMC: 6108420. DOI: 10.1038/nature25979. View

Chen Y, Bai J, Wu D, Yu S, Qiang X, Bai H . Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment response. J Affect Disord. 2019; 259:56-66. DOI: 10.1016/j.jad.2019.08.014. View

Ge X, Pan J, Liu Y, Wang H, Zhou W, Wang X . Intestinal Crosstalk between Microbiota and Serotonin and its Impact on Gut Motility. Curr Pharm Biotechnol. 2018; 19(3):190-195. DOI: 10.2174/1389201019666180528094202. View

10.

Bravo J, Forsythe P, Chew M, Escaravage E, Savignac H, Dinan T . Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011; 108(38):16050-5. PMC: 3179073. DOI: 10.1073/pnas.1102999108. View

11.

Cryan J, ORiordan K, Sandhu K, Peterson V, Dinan T . The gut microbiome in neurological disorders. Lancet Neurol. 2019; 19(2):179-194. DOI: 10.1016/S1474-4422(19)30356-4. View

12.

Wikoff W, Anfora A, Liu J, Schultz P, Lesley S, Peters E . Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A. 2009; 106(10):3698-703. PMC: 2656143. DOI: 10.1073/pnas.0812874106. View

13.

Sun M, Zhu Y, Zhou Z, Jia X, Xu Y, Yang Q . Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway. Brain Behav Immun. 2018; 70:48-60. DOI: 10.1016/j.bbi.2018.02.005. View

14.

Gao K, Pi Y, Mu C, Farzi A, Liu Z, Zhu W . Increasing carbohydrate availability in the hindgut promotes hypothalamic neurotransmitter synthesis: aromatic amino acids linking the microbiota-brain axis. J Neurochem. 2019; 149(5):641-659. DOI: 10.1111/jnc.14709. View

15.

Al-Jahmany A, Schultheiss G, Diener M . Effects of dopamine on ion transport across the rat distal colon. Pflugers Arch. 2004; 448(6):605-12. DOI: 10.1007/s00424-004-1299-9. View

16.

Bailey M, Cryan J . The microbiome as a key regulator of brain, behavior and immunity: Commentary on the 2017 named series. Brain Behav Immun. 2017; 66:18-22. DOI: 10.1016/j.bbi.2017.08.017. View

17.

Lee K, Kim J, Han S, Lee D, Lee H, Yim S . The extracellular vesicle of gut microbial Paenalcaligenes hominis is a risk factor for vagus nerve-mediated cognitive impairment. Microbiome. 2020; 8(1):107. PMC: 7364628. DOI: 10.1186/s40168-020-00881-2. View

18.

Hou Y, Shan C, Zhuang S, Zhuang Q, Ghosh A, Zhu K . Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson's disease. Microbiome. 2021; 9(1):34. PMC: 7849090. DOI: 10.1186/s40168-020-00988-6. View

19.

Bo T, Zhang X, Wen J, Deng K, Qin X, Wang D . The microbiota-gut-brain interaction in regulating host metabolic adaptation to cold in male Brandt's voles (Lasiopodomys brandtii). ISME J. 2019; 13(12):3037-3053. PMC: 6863827. DOI: 10.1038/s41396-019-0492-y. View

20.

Kang D, Adams J, Coleman D, Pollard E, Maldonado J, McDonough-Means S . Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci Rep. 2019; 9(1):5821. PMC: 6456593. DOI: 10.1038/s41598-019-42183-0. View