Psychobiotics, the Pharmacology of Probiotics, and Our Body’s Naturally Innate Pharmacy

It’s a little known fact that one of our body’s innate pharmacies resides in our gut.

Where, exactly, in our gut, you ask?

Well, in neurochemicals isolated in various microbial species whose diversity depends on our microbiome’s health. This speaks to another emerging area of interest: probiotics as pharmacy.

This article will briefly discuss five neurochemical isolated from various genera of normal gut bacteria:

1. GABA: Lactobacillus and Bifidobacterium. GABA is the main inhibitory neurotransmitter in the central nervous system, helping to induce a parasympathetic response, and significantly impacting and regulating various processes both physiologically and psychologically. Several animal studies indicate that various species of Lactobacillus and Bifidobacterium are capable of producing GABA in the gut. (1, 2, 3, 4)

2. Norepinephrine: Escherichia, Bacillus, and Saccharomyces. Norepinephrine is a naturally occurring neurotransmitter active during a sympathetic response which is upregulated during fight or flight and acts as a stress hormone. Several animal studies have shown that various species of Escherichia, Bacillus, and Saccharomyces play a role in upregulatting and producing norepinephrine. (5, 6, 7, 8)

3. Serotonin: Candida, Streptococcus, Escherichia, and Enterococcus. Serotonin is a key hormone, an estimated 90% of which is thought to be produced in the gut, that is key in mood stabilization and happiness, as well as impacting learning, attention, and memory processes. Several animal studies have indicate that various species of Candida, Streptococcus, Escherichia and Enterococcus play a role in serotonin production. (9, 10, 11, 12)

4. Dopamine: Bacillus and Serratia. Dopamine is a key neurotransmitter in our ability to experience pleasure, as well as cognitive control in our prefrontal cortext. Several animal studies have shown that certain species of Bacillus and Serratia play a key role in the production of dopamine. (13, 14)

5. Acetylcholine: Lactobacillus. Acetylcholine is the main neurotransmitter of the parasympathetic nervous system and its receptors are present all throughout our smooth muscle, blood vessels, and even heart muscle, as it helps to downregulate the function of certain organs during rest and digest. Several animal studies show that various species of Bacillus and Serratia are capable of producing acetylecholine in the gut. (15, 16)

Resources:

1. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF. 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 Sep 20;108(38):16050-5. doi: 10.1073/pnas.1102999108. Epub 2011 Aug 29. PMID: 21876150; PMCID: PMC3179073
2. Patterson E, Ryan PM, Wiley N, Carafa I, Sherwin E, Moloney G, Franciosi E, Mandal R, Wishart DS, Tuohy K, Ross RP, Cryan JF, Dinan TG, Stanton C. Gamma-aminobutyric acid-producing lactobacilli positively affect metabolism and depressive-like behaviour in a mouse model of metabolic syndrome. Sci Rep. 2019 Nov 8;9(1):16323. doi: 10.1038/s41598-019-51781-x. PMID: 31704943; PMCID: PMC6841999
3. Duranti, S., Ruiz, L., Lugli, G.A. et al. Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA. Sci Rep 10, 14112 (2020). https://doi.org/10.1038/s41598-020-70986-z
4. Yunes RA, Poluektova EU, Vasileva EV, Odorskaya MV, Marsova MV, Kovalev GI, Danilenko VN. A Multi-strain Potential Probiotic Formulation of GABA-Producing Lactobacillus plantarum 90sk and Bifidobacterium adolescentis 150 with Antidepressant Effects. Probiotics Antimicrob Proteins. 2020 Sep;12(3):973-979. doi: 10.1007/s12602-019-09601-1. PMID: 31677091
5. Lopes, J.G., Sourjik, V. Chemotaxis of Escherichia coli to major hormones and polyamines present in human gut. ISME J 12, 2736–2747 (2018). https://doi.org/10.1038/s41396-018-0227-5
6. Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Res. 2018;1693(Pt B):128-133. doi:10.1016/j.brainres.2018.03.015
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8. Malikina KD, Shishov VA, Chuvelev DI, Kudrin VS, Oleskin AV. [Regulatory role of monoamine neurotransmitters in Saccharomyces cerevisiae cells]. Prikl Biokhim Mikrobiol. 2010 Nov-Dec;46(6):672-7. Russian. PMID: 21261078
9. Mayr A, Hinterberger G, Dierich MP, Lass-Flörl C. Interaction of serotonin with Candida albicans selectively attenuates fungal virulence in vitro. Int J Antimicrob Agents. 2005;26(4):335-337. doi:10.1016/j.ijantimicag.2005.07.006
10. Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis [published correction appears in Cell. 2015 Sep 24;163:258]. Cell. 2015;161(2):264-276. doi:10.1016/j.cell.2015.02.047
11. Banskota S, Regmi SC, Gautam J, Gurung P, Lee YJ, Ku SK, Lee JH, Lee J, Chang HW, Park SJ, Kim JA. Serotonin disturbs colon epithelial tolerance of commensal E. coli by increasing NOX2-derived superoxide. Free Radic Biol Med. 2017 May;106:196-207. doi: 10.1016/j.freeradbiomed.2017.02.034. Epub 2017 Feb 17. PMID: 28216386
12. Evrensel A, Ceylan ME. The Gut-Brain Axis: The Missing Link in Depression. Clin Psychopharmacol Neurosci. 2015;13(3):239-244. doi:10.9758/cpn.2015.13.3.239
13. Liu J, Xu F, Nie Z, Shao L. Gut Microbiota Approach-A New Strategy to Treat Parkinson’s Disease. Front Cell Infect Microbiol. 2020;10:570658. Published 2020 Oct 22. doi:10.3389/fcimb.2020.570658
14. Zhu F, Li C, Chu F, Tian X, Zhu J. Target Dysbiosis of Gut Microbes as a Future Therapeutic Manipulation in Alzheimer’s Disease. Front Aging Neurosci. 2020;12:544235. Published 2020 Oct 6. doi:10.3389/fnagi.2020.544235
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16. Yong SJ, Tong T, Chew J, Lim WL. Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential. Front Neurosci. 2020;13:1361. Published 2020 Jan 14. doi:10.3389/fnins.2019.01361