Metabolites from the Gut Microbiota and the Role in the Gut-Brain Axis
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Published
Apr 30, 2022
Abstract
The gut microbiota is highly capable of biotransformation, exposing the host to a wide variety of physiologically active compounds. These metabolites participate in signaling between the gastrointestinal tract and the central nervous system and may regulate physiological and pathological processes in the central nervous system. This bidirectional communication can take place in a variety of ways, including binding to receptors in the host brain, stimulating the vagus nerve in the gut, modifying central neurotransmission, and influencing neuroinflam- mation. The purpose of this article is to discuss the mechanism of action of microbial metabolites such as short-chain fatty acids, bile acids, and neurotransmitters in the gut-brain axis and to propose new strategies for treating related neurological illnesses from a gut microbiota regulation perspective.
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Keywords
Gut Microbiota, Metabolites, Gut-Brain Axis, Central Nervous System, Neuromodulation
References
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2. Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol 2015; 28(2):203-209.
3. Dicks LMT, Hurn D, Hermanus D. Gut bacteria and neuropsychiatric disorders. Microorganisms 2021; 9(12):2583. DOI: https://doi.org/10.3390/microorganisms9122583
4. Clapp M, Aurora N, Herrera L, Bhatia M, Wilen E, Wakefield S. Gut microbiota's effect on mental health: The gut-brain axis. Clin Pract 2017; 7(4):987. DOI: https://doi.org/10.4081/cp.2017.987
5. Rios-Covian D, González S, Nogacka AM, Arboleya S, Salazar N, Gueimonde M, de Los Reyes-Gavilán CG. An overview on fecal branched short-chain fatty acids along human life and as related with body mass index: Associated dietary and anthropometric factors. Front Microbiol 2020; 11:973. DOI: https://doi.org/10.3389/fmicb.2020.00973
6. Hills RD Jr, Pontefract BA, Mishcon HR, Black CA, Sutton SC, Theberge CR. Gut Microbiome: Profound Implications for Diet and Disease. Nutrients 2019; 11(7):1613. DOI: https://doi.org/10.3390/nu11071613
7. Tian T, Zhao Y, Yang Y, Wang T, Jin S, Guo J, Liu Z. The protective role of short-chain fatty acids acting as signal molecules in chemotherapy- or radiation-induced intestinal inflammation. Am J Cancer Res 2020; 10(11):3508-3531.
8. Caspani G, Kennedy S, Foster JA, Swann J. Gut microbial metabolites in depression: understanding the biochemical mechanisms. Microb Cell 2019; 6(10):454-481. DOI: https://doi.org/10.15698/mic2019.10.693
9. Averina OV, Zorkina YA, Yunes RA, Kovtun AS, Ushakova VM, Morozova AY, Kostyuk GP, Danilenko VN, Chekhonin VP. Bacterial metabolites of human gut microbiota correlating with depression. Int J Mol Sci 2020; 21(23):9234. DOI: https://doi.org/10.3390/ijms21239234
10. Alagiakrishnan K, Halverson T. Microbial therapeutics in neurocognitive and psychiatric disorders. J Clin Med Res 2021; 13(9):439-459. DOI: https://doi.org/10.14740/jocmr4575
11. Zhu G, Zhao J, Zhang H, Chen W, Wang G. Administration of Bifidobacterium breve improves the brain function of Aβ1-42-treated mice via the modulation of the gut microbiome. Nutrients 2021; 13(5):1602. DOI: https://doi.org/10.3390/nu13051602
12. Metzdorf J, Tönges L. Short-chain fatty acids in the context of Parkinson's disease. Neural Regen Res 2021; 16(10):2015-2016. DOI: https://doi.org/10.4103/1673-5374.308089
13. Ho L, Ono K, Tsuji M, Mazzola P, Singh R, Pasinetti GM. Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer's disease-type beta-amyloid neuropathological mechanisms. Expert Rev Neurother 2018; 18(1):83-90. DOI: https://doi.org/10.1080/14737175.2018.1400909
14. Sadler R, Cramer JV, Heindl S, Kostidis S, Betz D, Zuurbier KR, Northoff BH, Heijink M, Goldberg MP, Plautz EJ, Roth S, Malik R, Dichgans M, Holdt LM, Benakis C, Giera M, Stowe AM, Liesz A. Short-chain fatty acids improve poststroke recovery via immunological mechanisms. J Neurosci 2020; 40(5):1162-1173. DOI: https://doi.org/10.1523/JNEUROSCI.1359-19.2019
15. Block RC, Dorsey ER, Beck CA, Brenna JT, Shoulson I. Altered cholesterol and fatty acid metabolism in Huntington disease. J Clin Lipidol 2010; 4(1):17-23. DOI: https://doi.org/10.1016/j.jacl.2009.11.003
16. Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, Harmsen HJM, Faber KN, Hermoso MA. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol 2019; 10:277. DOI: https://doi.org/10.3389/fimmu.2019.00277. Erratum in: Front Immunol 2019; 10:1486.
17. Sivaprakasam S, Prasad PD, Singh N. Benefits of short-chain fatty acids and their receptors in inflammation and carcinogenesis. Pharmacol Ther 2016; 164:144-151. DOI: https://doi.org/10.1016/j.pharmthera.2016.04.007
18. Wang Y, Wang Z, Wang Y, Li F, Jia J, Song X, Qin S, Wang R, Jin F, Kitazato K, Wang Y. The gut-microglia connection: Implications for central nervous system diseases. Front Immunol 2018; 9:2325. DOI: https://doi.org/10.3389/fimmu.2018.02325
19. Wu Y, Wang CZ, Wan JY, Yao H, Yuan CS. Dissecting the interplay mechanism between epigenetics and gut microbiota: Health maintenance and disease prevention. Int J Mol Sci 2021; 22(13):6933. DOI: https://doi.org/10.3390/ijms22136933
20. Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol (Lausanne) 2020; 11:25. DOI: https://doi.org/10.3389/fendo.2020.00025
21. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 2012; 61(2):364-371. DOI: https://doi.org/10.2337/db11-1019
22. Larraufie P, Martin-Gallausiaux C, Lapaque N, Dore J, Gribble FM, Reimann F, Blottiere HM. SCFAs strongly stimulate PYY production in human enteroendocrine cells. Sci Rep 2018; 8(1):74. DOI: https://doi.org/10.1038/s41598-017-18259-0
23. Byrne CS, Chambers ES, Morrison DJ, Frost G. The role of short chain fatty acids in appetite regulation and energy homeostasis. Int J Obes (Lond) 2015; 39(9):1331-1338. DOI: https://doi.org/10.1038/ijo.2015.84
24. van Son J, Koekkoek LL, La Fleur SE, Serlie MJ, Nieuwdorp M. The role of the gut microbiota in the gut-brain axis in obesity: Mechanisms and future implications. Int J Mol Sci 2021; 22(6):2993. DOI: https://doi.org/10.3390/ijms22062993
25. Yu KB, Hsiao EY. Roles for the gut microbiota in regulating neuronal feeding circuits. J Clin Invest 2021; 131(10):e143772. DOI: https://doi.org/10.1172/JCI143772
26. Frost G, Sleeth ML, Sahuri-Arisoylu M, Lizarbe B, Cerdan S, Brody L, Anastasovska J, Ghourab S, Hankir M, Zhang S, Carling D, Swann JR, Gibson G, Viardot A, Morrison D, Louise Thomas E, Bell JD. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun 2014; 5:3611. DOI: https://doi.org/10.1038/ncomms4611
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How to Cite
Fukushima, K. (2022). Metabolites from the Gut Microbiota and the Role in the Gut-Brain Axis. Science Insights, 40(5), 507–513. https://doi.org/10.15354/si.22.re037
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