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Effect of probiotic administration on gut microbiota and depressive behaviors in mice

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Abstract

Background

The gut microbiota is closely associated with the bidirectional gut-brain axis that modulates neuropsychological functions of the central nervous system, thereby affecting mental disorders such as depression. Although it is known that probiotics affect brain functions, the impact of probiotics on the regulation of the prevalence and composition of gut microbiota, leading to anti-depressive effects has not been well understood.

Methods

Mice were randomly divided into four different groups (n = 10 for each group) as follows: Group G1 (normal group) as control and group G2 (stress group) were given sterile saline via oral route daily for 8 weeks without and with stress condition, respectively. Under the stress condition, group G3 (fluoxetine group) was administered with fluoxetine hydrochloride and group G4 (probiotic group) was orally given multi-strains of probiotics daily for 8 weeks. After treatment, all mice underwent behavioral testing. Furthermore, fecal samples were collected from randomly selected 5 mice of each group on day 60 and taxonomical analysis of intestinal microbial distribution was performed.

Results

Mice subjected to restraint stress showed depressive-like behaviors along with high corticosterone levels in serum. However, probiotic administration alleviated depressive-like behaviors and decreased corticosterone level. Moreover, fecal microbiota was distinctly altered in probiotic-treated mice of the stress group. The relative abundance of phylum and genus levels was significantly decreased in the stress group, but probiotic administration restored the composition of microbes restored.

Conclusion

Ingested probiotics alter the composition of gut microbiota, likely improving the symptoms of depression.

Probiotic administration alters gut microbiota and reduces depressive-like behaviors

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References

  1. Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann General Psychiatry. 2017;16:18.

    Article  Google Scholar 

  2. Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJ, et al. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med. 2013;10:e1001547.

    Article  Google Scholar 

  3. Bostwick JM, Pankratz VS. Affective disorders and suicide risk: a reexamination. Am J Psychiatry. 2000;157:1925–32.

    Article  CAS  Google Scholar 

  4. Gump BB, Matthews KA, Eberly LE, Chang YF, Group MR. Depressive symptoms and mortality in men: results from the multiple risk factor intervention trial. Stroke. 2005;36:98–102.

    Article  Google Scholar 

  5. Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186–94.

    Article  Google Scholar 

  6. Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015;28:203–9.

    PubMed  PubMed Central  Google Scholar 

  7. Foster JA, McVey Neufeld KA. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013;36:305–12.

    Article  CAS  Google Scholar 

  8. Evrensel A, Ceylan ME. The gut-brain axis: the missing link in depression. Clin Psychopharmacol Neurosci. 2015;13:239–44.

    Article  CAS  Google Scholar 

  9. Rudzki L, Szulc A. “Immune gate” of psychopathology-the role of gut derived immune activation in major psychiatric disorders. Front Psychiatry. 2018;9:205.

    Article  Google Scholar 

  10. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008;29:117–24.

    PubMed  Google Scholar 

  11. Maes M, Kubera M, Leunis JC, Berk M. Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. J Affect Disord. 2012;141:55–62.

    Article  CAS  Google Scholar 

  12. Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers:Tthe gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015;9:392.

    PubMed  PubMed Central  Google Scholar 

  13. Ait-Belgnaoui A, Durand H, Cartier C, Chaumaz G, Eutamene H, Ferrier L, et al. Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology. 2012;37:1885–95.

  14. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. 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;108:16050–5.

  15. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008;43:164–74.

    Article  Google Scholar 

  16. Jeon S, Lee CH, Liu QF, Kim GW, Koo BS, Pak SC. Alteration in brain-derived neurotrophic factor (BDNF) after treatment of mice with herbal mixture containing Euphoria Longana. Houttuynia cordata and Dioscorea japonica Daru. 2014;22:77.

  17. Zeni AL, Zomkowski AD, Maraschin M, Rodrigues AL, Tasca CI. Ferulic acid exerts antidepressant-like effect in the tail suspension test in mice: evidence for the involvement of the serotonergic system. Eur J Pharmacol. 2012;679:68–74.

    Article  CAS  Google Scholar 

  18. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–6.

  19. Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013;74:720–6.

    Article  CAS  Google Scholar 

  20. Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan TG. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010;170:1179–88.

    Article  CAS  Google Scholar 

  21. McVey Neufeld KA, Kay S, Bienenstock J. Mouse strain affects behavioral and neuroendocrine stress responses following administration of probiotic Lactobacillus rhamnosus JB-1 or traditional antidepressant fluoxetine. Front Neurosci. 2018;12:294.

    Article  Google Scholar 

  22. Li N, Wang Q, Wang Y, Sun A, Lin Y, Jin Y, et al. Oral probiotics ameliorate the behavioral deficits induced by chronic mild stress in mice via the gut microbiota-inflammation axis. Front Behav Neurosci. 2018;12:266.

    Article  Google Scholar 

  23. Messaoudi M, Violle N, Bisson JF, Desor D, Javelot H, Rougeot C. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes. 2011;2:256–61.

    Article  Google Scholar 

  24. Rao AV, Bested AC, Beaulne TM, Katzman MA, Iorio C, Berardi JM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009;1:6.

    Article  Google Scholar 

  25. Zheng P, Cheng K, Zeng L, Zhou CJ, Xie P. A new pathway for the gut microbiota to modulate the brain: activation of pattern-recognition receptors by microbial products. Mol Psychiatry. 2017;22:162–3.

    Article  CAS  Google Scholar 

  26. Pfau ML, Menard C, Russo SJ. Inflammatory mediators in mood disorders: therapeutic opportunities. Annu Rev Pharmacol Toxicol. 2018;58:411–28.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education [2016R1D1A1B03932530 (B.S.K)].

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Author notes

  1. Quan Feng Liu and Hong-Man Kim contributed equally to this work.

Authors and Affiliations

  1. Department of Oriental Neuropsychiatry, Graduate School of Oriental Medicine, Dongguk University, Goyang, Republic of Korea

    Quan Feng Liu

  2. Cell Biotech R&D Center, Gimpo, Republic of Korea

    Hong-Man Kim, Sanghyun Lim & Myung-Jun Chung

  3. Department of Biostatistics, College of Medicine, Dongguk University, Goyang, Republic of Korea

    Chi-Yeon Lim

  4. Department of Oriental Medicine, Dongguk University, Gyeongju, Republic of Korea

    Byung-Soo Koo

  5. Department of Food Science and Biotechnology, College of Life Science and Biotechnology, Dongguk University, Goyang, Republic of Korea

    Seok-Seong Kang

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  1. Quan Feng Liu
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Correspondence to Byung-Soo Koo or Seok-Seong Kang.

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Liu, Q.F., Kim, HM., Lim, S. et al. Effect of probiotic administration on gut microbiota and depressive behaviors in mice. DARU J Pharm Sci 28, 181–189 (2020). https://doi.org/10.1007/s40199-020-00329-w

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  • DOI: https://doi.org/10.1007/s40199-020-00329-w

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