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A Multi-strain Potential Probiotic Formulation of GABA-Producing Lactobacillus plantarum 90sk and Bifidobacterium adolescentis 150 with Antidepressant Effects

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Abstract

Today, a number of studies conclusively show that certain bacterial strains, mainly from the genera Lactobacillus and Bifidobacterium, influence the functioning of the central nervous system, leading to changes in beahvior, nociception and the cognitive abilities of humans and animals. Such strains serve as the basis for developing probiotics with a curative potential for the central nervous system — psychobioitcs. However, the question of how to find such strains and which criteria to use for their selection remains unanswered. Some compounds produced by bacteria, such as gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter of the central nervous system, are potential mediators between bacterial cells and the host. Previously, we established that some species of Lactobacillus and Bifidobacterium are capable of producing GABA. We presumed that GABA-producing Lactobacillus and Bifidobacterium strains are great candidates to use as psychobiotics. Therefore, we selected the strains Lactobacillus plantarum 90sk and Bifidobacterium adolescentis 150 as efficient GABA producers. The goal of this work was to assess the probiotic properties of the selected strains as well as their antidepressive effects in mice. We established that the ingestion of the probiotic composition based on the selected strains by BALB/c mice for 2 weeks reduced depressive-like behavior in the forced swimming test; the effect was similar to that of fluoxetine.

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References

  1. Lankelma JM, Nieuwdorp M, de Vos WM, Wiersinga WJ (2015) The gut microbiota in internal medicine: implications for health and disease. Neth J Med 73:61–68

    CAS  PubMed  Google Scholar 

  2. Linares DM, Ross P, Stanton C (2016) Beneficial microbes: the pharmacy in the gut. Bioengineered 7(1):11–20. https://doi.org/10.1080/21655979.2015.1126015

    Article  CAS  PubMed  Google Scholar 

  3. Foster JA, McVey Neufeld KA (2013) Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 36(5):305–312. https://doi.org/10.1016/j.tins.2013.01.005

    Article  CAS  PubMed  Google Scholar 

  4. Dinan TG, Stanton C, Cryan JF (2013) Psychobiotics: a novel class of psychotropic. Biol Psychiatry 74:720–726. https://doi.org/10.1016/j.biopsych.2013.05.001

    Article  CAS  PubMed  Google Scholar 

  5. Bambury A, Sandhu K, Cryan JF, Dinan TG (2017) Finding the needle in the haystack: systematic identification of psychobiotics. Br J Pharmacol 175(24):4430–4438. https://doi.org/10.1111/bph.14127

    Article  CAS  Google Scholar 

  6. Hughes DT, Sperandio V (2008) Inter-kingdom signalling: communication between bacteria and their hosts. Nat Rev Microbiol 6(2):111–120. https://doi.org/10.1038/nrmicro1836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Averina OV, Danilenko VN (2017) Human intestinal microbiota: role in development and functioning of the nervous system. Microbiology (Mikrobiologiya) 86(1):1–18. https://doi.org/10.1134/S0026261717010040

    Article  CAS  Google Scholar 

  8. Kovtun AS, Averina OV, Zakharevich NV, Kasianov AS, Danilenko VN (2018) In silico identification of metagenomic signature describing neurometabolic potential of normal human gut microbiota. Russian Journal of Genetics. 54(9):1101–1110. https://doi.org/10.1134/S1022795418090089

    Article  CAS  Google Scholar 

  9. Valles-Colomer M, Falony G, Darzi Y, Tigchelaar EE, Wang J et al (2019) The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiol. 4:623–632. https://doi.org/10.1038/s41564-018-0337-x

    Article  CAS  Google Scholar 

  10. Roshchina VV (2016) New trends and perspectives in the evolution of neurotransmitters in microbial, plant, and animal cells. Adv Exp Med Biol 874:25–77. https://doi.org/10.1007/978-3-319-20215-0_2

    Article  CAS  PubMed  Google Scholar 

  11. Kakee A, Takanaga H, Terasaki T, Naito M, Tsuruo T, Sugiyama Y (2001) Efflux of a suppressive neurotransmitter, GABA, across the blood-brain barrier. J Neurochem 79(1):110–118

    Article  CAS  Google Scholar 

  12. Constans C, Ahnine H, Santin M, Lehericy S, Tanter M, Pouget P, Aubry J-F (2018) Non-invasive ultrasonic modulation of visual evoked response by GABA delivery through the blood brain barrier. bioRxiv 351270. https://doi.org/10.1101/351270

  13. Auteri M, Zizzo MG, Serio R (2015) GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation. Pharmacol Res 93:11–21. https://doi.org/10.1016/j.phrs.2014.12.001

    Article  CAS  PubMed  Google Scholar 

  14. Dhakal R, Bajpai VK, Baek K-H (2012) Production of GABA (γ – aminobutiric acid) by microorganisms: a review. Brazilian J Microbiol 43(4):1230–1241. https://doi.org/10.1590/S1517-83822012000400001

    Article  CAS  Google Scholar 

  15. Yunes RA, Poluektova EU, Dyachkova MS, Klimina KM, Kovtun AS, Averina OV, Orlova VS, Danilenko VN (2016) GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota. Anaerobe 42:197–204. https://doi.org/10.1016/j.anaerobe.2016.10.011

    Article  CAS  PubMed  Google Scholar 

  16. Pokusaeva K, Johson C, Luk B, Uribe G, Fu Y, Oezguen N et al (2016) GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine. Neurogastroenterol.Motil 29(1). https://doi.org/10.1111/nmo.12904

  17. Barrett E, Ross RP, O'Toole PW, Fitzgerald GF, Stanton C (2012) γ-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113(2):411–417. https://doi.org/10.1111/j.1365-2672.2012.05344.x

    Article  CAS  PubMed  Google Scholar 

  18. Mazzoli R, Pessione E (2016) The neuro-endocrinological role of microbial glutamate and GABA signaling. Front Microbiol 7:1934. https://doi.org/10.3389/fmicb.2016.01934

    Article  PubMed  PubMed Central  Google Scholar 

  19. Dyachkova MS, Klimina,KM, Kovtun,AS, Zakharevich NV, Nezametdinova VZ, Averina OV, Danilenko VN (2015) Draft genome sequences of Bifidobacterium angulatum GT102 and Bifidobacterium adolescentis 150: focusing on the genes potentially involved in the gut-brain axis. Genome Annouc 3(4): e00709-e00715. https://doi.org/10.1128/genomeA.00709-15

  20. De Man JC, Rogosa M, Sharpe ME (1960) A medium for the cultivation of lactobacilli. J App Microbiol 23:130–135. https://doi.org/10.1111/j.1365-2672.1960.tb00188.x

    Article  Google Scholar 

  21. Chervinets Y, Chervinets V, Shenderov B, Belyaeva E, Troshin A, Lebedev S, Danilenko V (2018) Adaptation and probiotic potential of lactobacilli isolated from the oral cavity and intestines of healthy people. Probiotics Antimicrob Proteins 10(1):22–33. https://doi.org/10.1007/s12602-017-9348-9

    Article  CAS  PubMed  Google Scholar 

  22. Kotova VY, Manukhov IV, Zavilgelskii GB (2010) Lux-biosensors for detection of SOS-response, heat shock, and oxidative stress. Appl Biochem Microbiol 46:781–788. https://doi.org/10.1134/S0003683810080089

    Article  CAS  Google Scholar 

  23. Marsova,M, Abilev S, Poluektova E, Danilenko V (2018) A bioluminescent test system reveals valuable antioxidant properties of lactobacillus strains from human microbiota. World J Microbiol Biotechnol 34(2):27. https://doi.org/10.1007/s11274-018-2410-2, 29

  24. Lucki I, Dalvi A, Mayorga A (2001) Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology (Berl) 155:315–322

    Article  CAS  Google Scholar 

  25. Porsolt RD, Bertin A, Jalfre M (1978) “Behavioural despair” in rats and mice: strain differences and the effects of imipramine. Eur J Pharmacol 51(3):291–294

    Article  CAS  Google Scholar 

  26. World Health Organization (2017) Depression and other common mental disorders: global health estimates. Licence CC BY-NC-SA 3.0 IGO, Geneva.

  27. Gayathri D, Rashmi BS (2017) Mechanism of development of depression and probiotics as adjuvant therapy for its prevention and management. Mental Health & Prevention 5:40–51. https://doi.org/10.1016/j.mhp.2017.01.003

    Article  Google Scholar 

  28. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA 108(38):16050–16055. https://doi.org/10.1073/pnas.1102999108

    Article  PubMed  Google Scholar 

  29. Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, Bisson JF, Rougeot C, Pichelin M, Cazaubiel M, Cazaubiel JM (2011) Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr 105(5):755–764. https://doi.org/10.1017/S0007114510004319

    Article  CAS  PubMed  Google Scholar 

  30. Ko Y, Lin H-TV, Tsai GJ (2013) Gamma-aminobutyric acid production in black soybean milk by Lactobacillus brevis FPA 3709 and the antidepressant effect of the fermented product on a forced swimming rat model. Process Biochemistry 48(4):559–568. https://doi.org/10.1016/j.procbio.2013.02.021

    Article  CAS  Google Scholar 

  31. Savignac HM, Kiely B, Dinan TG, Cryan JF (2014) Bifidobacteria exert strainspecific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil 26(11):1615–1627. https://doi.org/10.1111/nmo.12427

    Article  CAS  PubMed  Google Scholar 

  32. Liu YW, Liu WH, Wu CC, Juan YC, Wu YC, Tsai HP, Wang S, Tsai YC (2016) Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naïve adult mice. Brain Res 1631:1–12. https://doi.org/10.1016/j.brainres.2015.11.018

    Article  CAS  PubMed  Google Scholar 

  33. Messaoudi M, Violle N, Bisson JF, Desor D, Javelot H, Rougeot C (2011b) Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes 2(4):256–261. https://doi.org/10.4161/gmic.2.4.16108

    Article  PubMed  Google Scholar 

  34. Akkasheh G, Kashani-Poor Z, Tajabadi-Ebrahimi M, Jafari P, Akbari H, Taghizadeh M, Memarzadeh MR, Asemi Z, Esmaillzadeh A (2016) Clinical and metabolic response to probiotic administration in patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial. Nutrition 32(3):315–320. https://doi.org/10.1016/j.nut.2015.09.003

    Article  CAS  PubMed  Google Scholar 

  35. Allen AP, Hutch W, Borre YE, Kennedy PJ, Temko A, Boylan G, Murphy E, Cryan JF, Dinan TG, Clarke G (2016) Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology, and neurocognition in healthy volunteers. Transl Psychiatry 6(11):e939. https://doi.org/10.1038/tp.2016.191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wallace CJK, Milev R (2017) The effects of probiotics on depressive symptoms in humans: a systematic review. Annals of General Psychiatry 16:14. https://doi.org/10.1186/s12991-017-0138-2

    Article  PubMed  PubMed Central  Google Scholar 

  37. Chiu TH, Tsai SJ, Wu TY, Fu SC, Hwang YT (2013) Improvement in antioxidant activity, angiotensin-converting enzyme inhibitory activity and in vitro cellular properties of fermented pepino milk by Lactobacillus strains containing the glutamate decarboxylase gene. J Sci Food Agric 93(4):859–866. https://doi.org/10.1002/jsfa.5809

    Article  CAS  PubMed  Google Scholar 

  38. Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H (2002) GABA and GABA receptors in the central nervous system and other organs. Intern Rev Cytology 213: 1-47. https://doi.org/10.1016/S0074-7696(02)13011-7

  39. Ait-Belgnaoui A, Payard I, Rolland C, Harkat C, Braniste V, Théodorou V, Tompkins TA (2018) Bifidobacterium longum and Lactobacillus helveticus synergistically suppress stress-related visceral hypersensitivity through hypothalamic-pituitary-adrenal axis modulation. J Neurogastroenterol Motil 24(1):138–146. https://doi.org/10.5056/jnm16167

    Article  PubMed  PubMed Central  Google Scholar 

  40. Bambling M, Edwards SC, Hall S, Vitetta L (2017) A combination of probiotics and magnesium orotate attenuate depression in a small SSRI resistant cohort: an intestinal anti-inflammatory response is suggested. Inflammopharmacology 25(2):271–274. https://doi.org/10.1007/s10787-017-0311-x

    Article  CAS  PubMed  Google Scholar 

  41. Hennessy AA, Ross RP, Devery R, Stanton C (2011) The health promoting properties of the conjugated isomers of α-linolenic acid. Lipids 46(2):105–119. https://doi.org/10.1007/s11745-010-3501-5

    Article  CAS  PubMed  Google Scholar 

  42. Levy M, Blacher E, Elinav E (2017) Microbiome, metabolites and host immunity. Curr Opin Microbiol 35:8–15. https://doi.org/10.1016/j.mib.2016.10.003

    Article  CAS  PubMed  Google Scholar 

  43. Kelly JR, Allen AP, Temko A, Hutch W, Kennedy PJ, Farid N, Murphy E, Boylan G, Bienenstock J, Cryan JF, Clarke G, Dinan TG (2017) Lost in translation? The potential psychobiotic Lactobacillus rhamnosus JB-1 fails to modulate stress or cognitive performance in healthy male subjects. Brain Behav Immun 61:50–59. https://doi.org/10.1016/j.bbi.2016.11.018

    Article  CAS  PubMed  Google Scholar 

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Funding

This project was funded by the state budget reserved for “Genetic technologies in biology, medicine, agricultural and environmental activities N 0112-2019-0002.”

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Correspondence to R. A. Yunes.

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The experiments were approved by a Bioethics Committee of the Research Zakusov Institute of Pharmacology. The animals were handled in accordance with the guidelines set by the directive of the Ministry of Health of the Russian Federation (23.08.2010, N2708N).

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Yunes, R.A., Poluektova, E.U., Vasileva, E.V. et al. A Multi-strain Potential Probiotic Formulation of GABA-Producing Lactobacillus plantarum 90sk and Bifidobacterium adolescentis 150 with Antidepressant Effects. Probiotics & Antimicro. Prot. 12, 973–979 (2020). https://doi.org/10.1007/s12602-019-09601-1

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