To the content
2 . 2021

Antioxidant and anxiolytic effect of Bifidobacterium adolescentis and Lactobacillus acidophilus under conditions of normobaric hypoxia with hypercapnia

Abstract

Research in recent years has shown that there is a close connection between the brain and the intestine through neuronal, endocrine and immune pathways. The introduction of probiotics into the diet of animals and humans helps to reduce the level of anxiety and depression, as well as inflammatory processes during emotional stress.

The aim of this work was to study the effect of intragastric administration of Bifidobacterium adolescentis and Lactobacillus acidophilus on oxidative processes in the brain tissues and the level of anxiety in rats under conditions of normoxia and acute hypoxia with hypercapnia.

Material and methods. The experiment was performed on 64 male Wistar rats aged 2.5 months (body weight from 240 to 270 g). The animals were divided into 4 groups: group 1 - control; 2 - hypoxia; 3 - hypoxia + probiotics; 4 - probiotics. There were 16 animals in each group; half of them participated in the behavioral test, and the other half in the biochemical studies. Rats of groups 3 and 4 were orally administered lyophilized bacteria Bifidobacterium adolescentis MC-42, Lactobacillus acidophilus A-97, and Lactobacillus acidophilus A-630for 30 days before hypoxia. The daily dose of probiotics was 1x109 CFU per animal, administered in a volume of 1 ml. Acute hypoxia with hypercapnia was simulated by placing rats in airtight vessels with a capacity of 1L before the first agonal inhalation. A day later, in the brain tissues oxidative processes were assessed by the chemiluminescence method and by the level of malone dialdehyde (MDA). The activity of catalase in brain tissues was also determined. The level of anxiety of rats was investigated in the «elevated plus maze» test.

Results. Compared to other groups, more intensive free radical oxidation took place in the brain tissues of hypoxified animals that did not receive B. adolescentis and L. acidophilus. There was a significant increase in chemiluminescence intensity and MDA level by 38 and 15%, respectively, compared with the control. In the brain tissues of these animals, catalase activity was reduced by 10% (p<0.01). Moreover, in the group of rats treated with B. adolescentis and L. acidophilus and subjected to acute hypoxia, the value of the light sum of chemiluminescence was 22% lower (p<0.01) than in the hypoxified group without taking probiotics, while the concentration of MDA and catalase activity remained at the level of physiological norms and did not differ from control. Hypoxified animals receiving biomass of lactobacteria and bifidobacteria had also a lower level of anxiety and a higher exploratory activity, expressed in an increase in the number of entries in the open and closed arms, a longer stay in the open arms and the center of the maze, and more frequent performance of orientation reactions and hanging.

Conclusion. Pre-hypoxic administration of B. adolescentis and L. acidophilus reduces the development of oxidative stress in rat brain tissues and reduces anxiety indices in the “elevatedplus maze” test, thereby exhibiting antioxidant and anxiolytic effects.

Keywords:hypercapnic hypoxia, probiotics, Bifidobacterium adolescentis, Lactobacillus acidophilus, malone dialdehyde, chemiluminescence, catalase, anxiety

Funding. The study was not sponsored.

Conflict of interests. The authors declare no conflicts of interest.

For citation: Kozin S.V., Kravtsov A.A., Kravchenko S.V., Ivashchenko L.I. Antioxidant and anxiolytic effect of Bifidobacterium adolescentis and Lactobacillus acidophilus under conditions of normobaric hypoxia with hypercapnia. Voprosy pitaniia [Problems of Nutrition]. 2021; 90 (2): 63-72. DOI: https://doi.org/10.33029/0042-8833-2021-90-2-63-72 (in Russian)

References

1. Vetrovoy O.V., Rybnikova E.A., Samoylov M.O. Cerebral mechanisms of hypoxic/ischemic postconditioning. Biokhimiya [Biochemistry]. 2017; 82 (3): 392–400. DOI: https://doi.org/10.1134/S000629791703018X (in Russian)

2. Lee R.H.C., Lee M.H.H., Wu C.Y.C., Couto e Silva A., Possoit H.E., Hsieh T.H., et al. Cerebral ischemia and neuroregeneration. Neural Regen Res. 2018; 13 (3): 373–85. DOI: https://doi.org/10.4103/1673-5374.228711

3. Paolucci S., Iosa M., Coiro P., Venturiero V., Savo A., De Angelis D., et al. Post-stroke depression increases disability more than 15% in ischemic stroke survivors: a case-control study. Front Neurol. 2019; 10: 926. DOI: https://doi.org/10.3389/fneur.2019.00926

4. Voronina T.A. The role of hypoxia in stroke and convulsive states. Antihypoxants. Obzory po klinicheskoy farmakologii i lekarstvennoy terapii [Reviews on Clinical Pharmacology and Drug Therapy]. 2016; 14 (1): 63–79. DOI: https://doi.org/10.17816/RCF14163-70 (in Russian)

5. Latorre R., Sternini C., De Giorgio R., Greenwood-Van Meerveld B. Enteroendocrine cells: a review of their role in brain-gut communication. Neurogastroenterol Motil. 2016; 28 (5): 620–30. DOI: https://doi.org/10.1111/nmo.12754

6. Savignac H.M., Tramullas M., Kiely B., Dinan T.G. Bifidobacteria modulate cognitive processes in an anxious mouse strain. Behav Brain Res. 2015; 287: 59–72. DOI: https://doi.org/10.1016/j.bbr.2015.02.044

7. Savignac H.M., Kiely B., Dinan T.G., Cryan J.F. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil. 2014; 26 (11): 1615–27. DOI: https://doi.org/10.1111/nmo.12427

8. Bercik P., Park A.J., Sinclair D., Khoshdel A., Lu J., Huang X., et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil. 2011; 23 (12): 1132–9. DOI: https://doi.org/10.1111/j.1365-2982.2011.01796.x

9. Arseneault-Bréard J., Rondeau I., Gilbert K., Girard Stéphanie-Anne, Tompkins T.A., Godbout R., et al. Combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces post-myocardial infarction depression symptoms and restores intestinal permeability in a rat model. Br J Nutr. 2012; 107 (12): 1793–9. DOI: https://doi.org/10.1017/S0007114511005137

10. Battaglini D., Pimentel-Coelho P.M., Robba C., Dos Santos C.C., Cruz F.F., Pelosi P., et al. Gut microbiota in acute ischemic stroke: from pathophysiology to therapeutic implications. Front Neurol. 2020; 11: 598. DOI: https://doi.org/10.3389/fneur.2020.00598

11. Akhoundzadeh K., Vakili A., Shadnoush M., Sadeghzadeh J. Effects of the oral ingestion of probiotics on brain damage in a transient model of focal cerebral ischemia in mice. Iran J Med Sci. 2018; 43 (1): 32–40. PMCID: PMC5775992.

12. Rahmati H., Momenabadi S., Vafaei A.A., Bandegi A. R., Mazaheri Z., Vakili A. Probiotic supplementation attenuates hippocampus injury and spatial learning and memory impairments in a cerebral hypoperfusion mouse model. Mol Biol Rep. 2019; 46 (5): 4985–95. DOI: https://doi.org/10.1007/s11033-019-04949-7

13. Yamashiro K., Tanaka R., Urabe T., Ueno Y., Yamashiro Y., Nomoto K., et al. Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke. PLoS One. 2017; 12 (2). DOI: https://doi.org/10.1371/journal.pone.0176062

14. Rice M.W., Pandya J.D., Shear D.A. Gut microbiota as a therapeutic target to ameliorate the biochemical, neuroanatomical, and behavioral effects of traumatic brain injuries. Front Neurol. 2019; 10: 875. DOI: https://doi.org/10.3389/fneur.2019.00875

15. Sun M.F., Shen Y.Q. Dysbiosis of gut microbiota and microbial metabolites in Parkinson’s disease. Ageing Res Rev. 2018; 45: 53–61. DOI: https://doi.org/10.1016/j.arr.2018.04.004

16. Gazerani P. Probiotics for Parkinson’s disease. Int J Mol Sci. 2019; 20 (17): 4121. DOI: https://doi.org/10.3390/ijms20174121

17. Kouchaki E., Tamtaji O.R., Salami M., Bahmani F., Kakhaki R.D., Akbari E., et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2017; 36 (5): 1245–9. DOI: https://doi.org/10.1016/j.clnu.2016.08.015

18. Tian P., Wang G., Zhao J., Zhang H., Chen W. Bifidobacterium with the role of 5-hydroxytryptophan synthesis regulation alleviates the symptom of depression and related microbiota dysbiosis. J Nutr Biochem. 2019; 66: 43–51. DOI: https://doi.org/10.1016/j.jnutbio.2019.01.007

19. Duranti S., Ruiz L., Lugli G.A., Tames H., Milani C., Mancabelli L., et al. Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA. Sci Rep. 2020; 10 (1): 14112. DOI: https://doi.org/10.1038/s41598-020-70986-z

20. Yunes R.A., Poluektova E.U., Dyachkova M.S., Klimina K.M., Kovtun A.S., Averina O.V., et al. GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota. Anaerobe. 2016; 42: 197–204. DOI: https://doi.org/10.1016/j.anaerobe.2016.10.011

21. Barrett E., Ross R.P., O’Toole P.W., Fitzgerald G.F., Stanton C. γ-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol. 2012; 113 (2): 411–7. DOI: https://doi.org/10.1111/j.1365-2672.2012.05344.x

22. Oleskin A.V., Shenderov B.A., Rogovsky V.S. Role of neurochemicals in the interaction between the microbiota and the immune and the nervous system of the host organism. Probiotics Antimicrob Proteins. 2017; 9 (3): 215–34. DOI: https://doi.org/10.1007/s12602-017-9262-1

23. Ferrer I., Vidal N. Neuropathology of cerebrovascular diseases. Handb Clin Neurol. 2017; 145: 79–114. DOI: https://doi.org/10.1016/B978-0-12-802395-2.00007-9

24. Rahaman P., Del Bigio M.R. Histology of brain trauma and hypoxia-ischemia. Acad Forensic Pathol. 2018; 8 (3): 539–54. DOI: https://doi.org/10.1177/1925362118797728

25. Buresh Ya., Bureshova O., H’yuston D.P. Methods and basic experiments for studying the brain and behavior. Moscow: Vysshaya shkola, 1991: 399 p. (in Russian)

26. Habriev R.U. Guidelines for experimental (preclinical) study of new pharmacological substances. Moscow: Meditsina, 2005: 832 p. (in Russian)

27. Farkhutdinov R.R., Likhovskikh V.A. Chemiluminescent methods for studying free radical oxidation in biology and medicine. Ufa, 1995: 87 p. (in Russian)

28. Gavrilov V.B., Gavrilova A.R., Mazhul’ L.M. Analysis of the procedures for estimation of lipid peroxidation products using thiobarbituric acid test. Voprosy meditsinskoy khimii [Problems of Medical Chemistry]. 1987; 33 (1): 118–22. (in Russian)

29. Korolyuk M.A., Ivanova L.I., Mayorova I.G., Tokarev V.E. Method for determining catalase activity. Laboratornoe delo [Laboratory Work]. 1988; (1): 16–9. (in Russian)

30. Surace M.J., Block M.L. Targeting microglia-mediated neurotoxicity: the potential of NOX2 inhibitors. Cell Mol Life Sci. 2012; 69 (14): 2409–27. DOI: https://doi.org/10.1007/s00018-012-1015-4

31. Pace T.W., Hu F., Miller A.H. Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun. 2007; 21 (1): 9–19. DOI: https://doi.org/10.1016/j.bbi.2006.08.009

32. van der Kleij H., O’Mahony C., Shanahan F., O’Mahony L., Bienenstock J. Protective effects of Lactobacillus rhamnosus [corrected] and Bifidobacterium infantis in murine models for colitis do not involve the vagus nerve. Am J Physiol Regul Integr Comp Physiol. 2008; 295 (4): 1131–7. DOI: https://doi.org/10.1152/ajpregu.90434.2008

33. Quaresma M., Damasceno S., Monteiro C., Lima F., Mendes T., Lima M., et al. Probiotic mixture containing Lactobacillus spp. and Bifidobacterium spp. attenuates 5-fluorouracil-induced intestinal mucositis in mice. Nutr Cancer. 2020; 72 (8): 1355–65. DOI: https://doi.org/10.1080/01635581.2019.1675719

34. Yano J.M. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015; 161 (2): 264–76. DOI: https://doi.org/10.1016/j.cell.2015.02.047

35. Oleskin A.V., Shenderov B.A. Probiotics and psychobiotics: the role of microbial neurochemicals. Probiotics Antimicrob Proteins. 2019; 11 (4): 1071–85. DOI: https://doi.org/10.1007/s12602-019-09583-0

36. Guo Y., Xie J.P., Deng K., Li X., Yuan Y., Xuan Q., et al. Prophylactic effects of Bifidobacterium adolescentis on anxiety and depression-like phenotypes after chronic stress: a role of the gut microbiota-inflammation axis. Front Behav Neurosci. 2019; 13: 126. DOI: https://doi.org/10.3389/fnbeh.2019.00126

37. Desbonnet L., Garrett L., Clarke G., Bienenstock J., Dinan T.G. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008; 43 (2): 164–74. DOI: https://doi.org/10.1016/j.jpsychires.2008.03.009

38. Swaab D.F., Bao A.M., Lucassen P.J. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev. 2005; 4 (2): 141–94. DOI: https://doi.org/10.1016/j.arr.2005.03.003

39. Agus A., Planchais J., Sokol H. Gut Microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe. 2018; 23 (6): 716–24. DOI: https://doi.org/10.1016/j.chom.2018.05.003

40. Baj A., Moro E., Bistoletti M., Orlandi V., Crema F., Giaroni C. Glutamatergic signaling along the microbiota-gut-brain axis. Int J Mol Sci. 2019; 20 (6): 1482. DOI: https://doi.org/10.3390/ijms20061482

41. Du Y., Gao X.R., Peng L., Ge J.F. Crosstalk between the microbiota-gut-brain axis and depression. Heliyon. 2020; 6 (6): e04097. DOI: https://doi.org/10.1016/j.heliyon.2020.e04097

42. Mayer E.A. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci. 2011; 12 (8): 453–66. DOI: https://doi.org/10.1038/nrn3071

43. Andersson U., Tracey K.J. Reflex principles of immunological homeostasis. Annu Rev Immunol. 2012; 30: 313–35. DOI: https://doi.org/10.1146/annurev-immunol-020711-075015

44. Altavilla D., Guarini S., Bitto A., Mioni C., Giuliani D., Bigiani A., et al. Activation of the cholinergic anti-inflammatory pathway reduces NF-kappab activation, blunts TNF-alpha production, and protects against splanchic artery occlusion shock. Shock. 2006; 25 (5): 500–6. DOI: https://doi.org/10.1097/01.shk.0000209539.91553.82

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

SCImago Journal & Country Rank
Scopus CiteScore
CHIEF EDITOR
CHIEF EDITOR
Viktor A. Tutelyan
Full Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Scientific Director of the Federal Research Centre of Nutrition, Biotechnology and Food Safety (Moscow, Russia)

Journals of «GEOTAR-Media»