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Psychobiotic interventions attenuate chronic alcohol use-mediated exacerbation of posttraumatic stress disorder in rats: the role of gut-liver axis response

  • Elizabeth T. Akinluyi EMAIL logo , Edem E. Edem , Kelvin M. Dakoru , Chinaza J. Nnodim , Michael A. Oladipupo , Olusegun A. Adeoluwa , Abiola O. Obisesan , Benneth Ben-Azu and Olusegun G. Adebayo
Published/Copyright: December 21, 2022

Abstract

Objectives

The incidence of co-occurring alcohol-use disorder (AUD) and post-traumatic stress disorder (PTSD) is high, and the presence of one disorder aggravates the severity of the other. Emerging evidence shows the neuroprotective and anti-inflammation functions of psychobiotics. Hence, the study explored the effects of probiotics and synbiotic inulin on the gut- and liver-oxidative and inflammatory biomarkers in chronic alcohol exacerbation of PTSD symptoms in rats.

Methods

Young adult rats were administered 10% ethanol in a two-bottle choice test for six weeks and were subjected to single prolonged stress. Probiotics and synbiotic intervention followed this. Markers of oxido-inflammatory stress, liver functions, intestinal (faecal) metabolites, occludin expression, and histopathology of the ileum and liver were evaluated.

Results

Chronic alcohol drinking and PTSD increased oxido-inflammatory stress, markers of hepatic damage, and reduced faecal metabolites, which were attenuated by probiotic and synbiotic interventions. Furthermore, reduced immunoexpression of gut and liver occludin, with loss of barrier integrity, viable hepatocytes, congestive portal area, and shortened villi and crypt depth, were observed. Probiotic and synbiotic interventions mitigated these effects.

Conclusions

The study demonstrates that psychobiotics mitigate the detrimental effects of co-occurring chronic alcohol intake in the context of PTSD.


Corresponding author: Elizabeth T. Akinluyi, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Afe Babalola University, Ado- Ekiti, Nigeria, E-mail:
Kelvin M. Dakoru, Chinaza J. Nnodim, and Michael A. Oladipupo contributed equally to this work.

Acknowledgments

The authors wish to acknowledge the technical staff of the Department of Pharmacology and Therapeutics, Afe Babalola University, for their technical support.

  1. Research funding: The authors received no external funds for the research and publication of this article.

  2. Author contributions: Elizabeth T. Akinluyi: Conceptu-alization, Methodology, Supervision, Writing-Review & editing. Edem E. Edem: Conceptualization, Methodology, Writing-review & editing. Kelvin M. Dakoru, Chinaza J. Nnodim, and Michael A. Oladipupo: Investigation, Resources. Olusegun A. Adeoluwa: Methodology, Super-vision, Resources, Review. Abiola O. Obisesan: Resources, Supervision. Benneth Ben-Azu: Writing-Review and editing. Olusegun G. Adebayo: Writing-Original draft preparation.

  3. Competing interests: The authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: The study was approved by the Research Ethics Committee of the Afe Babalola University AB/EC/21/03/002.

References

1. Reus, VI, Fochtmann, LJ, Bukstein, O, Eyler, AE, Hilty, DM, Horvitz-Lennon, M, et al.. The American Psychiatric Association practice guideline for the pharmacological treatment of patients with alcohol use disorder. Am J Psychiatry 2018;175:86–90. https://doi.org/10.1176/appi.ajp.2017.1750101.Search in Google Scholar PubMed

2. Blanco, C, Xu, Y, Brady, K, Pérez-Fuentes, G, Okuda, M, Wang, S. Comorbidity of post-traumatic stress disorder with alcohol dependence among US adults: results from national epidemiological survey on alcohol and related conditions. Drug Alcohol Depend 2013;132:630–8. https://doi.org/10.1016/j.drugalcdep.2013.04.016.Search in Google Scholar PubMed PubMed Central

3. Sinha, R. How does stress lead to risk of alcohol relapse? Alcohol Res 2012;34:432–40.Search in Google Scholar

4. Gilpin, NW, Weiner, JL. Neurobiology of comorbid post-traumatic stress disorder and alcohol-use disorder. Genes Brain Behav 2017;16:15–43. https://doi.org/10.1111/gbb.12349.Search in Google Scholar PubMed PubMed Central

5. Fernández-Rodríguez, S, Cano-Cebrián, MJ, Rius-Pérez, S, Pérez, S, Guerri, C, Granero, L, et al.. Different brain oxidative and neuroinflammation status in rats during prolonged abstinence depending on their ethanol relapse-like drinking behavior: effects of ethanol reintroduction. Drug Alcohol Depend 2022;232:109284. https://doi.org/10.1016/j.drugalcdep.2022.109284.Search in Google Scholar PubMed

6. Wang, Z, Mandel, H, Levingston, CA, Young, MR. An exploratory approach demonstrating immune skewing and a loss of coordination among cytokines in plasma and saliva of Veterans with combat-related PTSD. Hum Immunol 2016;77:652–7. https://doi.org/10.1016/j.humimm.2016.05.018.Search in Google Scholar PubMed PubMed Central

7. Serova, LI, Laukova, M, Alaluf, LG, Pucillo, L, Sabban, EL. Intranasal neuropeptide Y reverses anxiety and depressive-like behavior impaired by single prolonged stress PTSD model. Eur Neuropsychopharmacol 2014;24:142–7. https://doi.org/10.1016/j.euroneuro.2013.11.007.Search in Google Scholar PubMed

8. Suh, J, Ressler, KJ. Common biological mechanisms of alcohol use disorder and post-traumatic stress disorder. Alcohol Res 2018;39:131–45.Search in Google Scholar

9. Shukla, PK, Meena, AS, Dalal, K, Canelas, C, Samak, G, Pierre, JF, et al.. Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis. Sci Rep 2021;11:1–8. https://doi.org/10.1038/s41598-020-80637-y.Search in Google Scholar PubMed PubMed Central

10. Petrakis, IL, Simpson, TL. Post-traumatic stress disorder and alcohol use disorder: a critical review of pharmacologic treatments. Alcohol Clin Exp Res 2017;41:226–37. https://doi.org/10.1111/acer.13297.Search in Google Scholar PubMed PubMed Central

11. Moya-Pérez, A, Perez-Villalba, A, Benitez-Paez, A, Campillo, I, Sanz, Y. Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice. Brain Behav Immun 2017;65:43–56. https://doi.org/10.1016/j.bbi.2017.05.011.Search in Google Scholar PubMed

12. Mazidi, M, Rezaie, P, Ferns, GA, Vatanparast, H. Impact of probiotic administration on serum C-reactive protein concentrations: systematic review and meta-analysis of randomized control trials. Nutrients 2017;9:20. https://doi.org/10.3390/nu9010020.Search in Google Scholar PubMed PubMed Central

13. Leclercq, S, Forsythe, P, Bienenstock, J. Posttraumatic stress disorder: does the gut microbiome hold the key? Can J Psychiatry 2016;6:204–13. https://doi.org/10.1177/0706743716635535.Search in Google Scholar PubMed PubMed Central

14. Leclercq, S, Stärkel, P, Delzenne, NM, de Timary, P. The gut microbiota: a new target in the management of alcohol dependence? Alcohol 2019;74:105–11. https://doi.org/10.1016/j.alcohol.2018.03.005.Search in Google Scholar PubMed

15. Hill, C, Guarner, F, Reid, G, Gibson, GR, Merenstein, DJ, Pot, B, et al.. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014;11:506–14. https://doi.org/10.1038/nrgastro.2014.66.Search in Google Scholar PubMed

16. Salami, M. Interplay of good bacteria and central nervous system: cognitive aspects and mechanistic considerations. Front Neurosci 2021;15:613120. https://doi.org/10.3389/fnins.2021.613120.Search in Google Scholar PubMed PubMed Central

17. Markowiak, P, Śliżewska, K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients 2017;9:1021. https://doi.org/10.3390/nu9091021.Search in Google Scholar PubMed PubMed Central

18. Panesar, PS, Shinde, C. Effect of storage on syneresis, pH, Lactobacillus acidophilus count, Bifidobacterium bifidum count of Aloe vera fortified probiotic yoghurt. Curr Res Dairy Sci 2014;4:17–23. https://doi.org/10.3923/crds.2012.17.23.Search in Google Scholar

19. Rao, M, Gao, C, Xu, L, Jiang, L, Zhu, J, Chen, G, et al.. Effect of inulin-type carbohydrates on insulin resistance in patients with type 2 diabetes and obesity: a systematic review and meta-analysis. J Diabetes Res 2019. https://doi.org/10.1155/2019/5101423. 31534973.Search in Google Scholar PubMed PubMed Central

20. Huang, CH, Ho, CY, Chen, CT, Hsu, HF, Lin, YH. Probiotic BSH activity and anti-obesity potential of Lactobacillus plantarum strain TCI378 isolated from Korean Kimchi. Prev Nutr Food Sci 2019;24:434. https://doi.org/10.3746/pnf.2019.24.4.434.Search in Google Scholar PubMed PubMed Central

21. Akram, W, Garud, N, Joshi, R. Role of inulin as prebiotics on inflammatory bowel disease. Drug Discoveries Ther 2019;13:1–8. https://doi.org/10.5582/ddt.2019.01000.Search in Google Scholar PubMed

22. Wang, L, Shang, Q, Guo, W, Wu, X, Wu, L, Wu, L, et al.. Evaluation of the hypoglycemic effect of probiotics via directly consuming glucose in intestines of STZ-induced diabetic mice and glucose water-induced diabetic mice. J Funct Foods 2020;64:103614. https://doi.org/10.1016/j.jff.2019.103614.Search in Google Scholar

23. Chitapanarux, I, Chitapanarux, T, Traisathit, P, Kudumpee, S, Tharavichitkul, E, Lorvidhaya, V. Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients. Radiat Oncol 2010;5:1–6. https://doi.org/10.1186/1748-717x-5-31.Search in Google Scholar

24. Carnicella, S, Ron, D, Barak, S. Intermittent ethanol access schedule in rats as a preclinical model of alcohol abuse. Alcohol 2014;48:243–52. https://doi.org/10.1016/j.alcohol.2014.01.006.Search in Google Scholar PubMed PubMed Central

25. Yuan, Y, Zhen, L, Li, Z, Xu, W, Leng, H, Xu, W, et al.. trans-Resveratrol ameliorates anxiety-like behaviors and neuropathic pain in mouse model of post-traumatic stress disorder. J Psychopharmacol 2020;34:726–36. https://doi.org/10.1177/0269881120914221.Search in Google Scholar PubMed

26. Zheng, K, Wu, L, He, Z, Yang, B, Yang, Y. Measurement of the total protein in serum by biuret method with uncertainty evaluation. Measurement 2017;112:16–21. https://doi.org/10.1016/j.measurement.2017.08.013.Search in Google Scholar

27. De Leon, JA, Borges, CR. Evaluation of oxidative stress in biological samples using the thiobarbituric acid reactive substances assay. JoVE 2020;159:e61122.Search in Google Scholar

28. Reitman, S, Frankel, S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56–63. https://doi.org/10.1093/ajcp/28.1.56.Search in Google Scholar PubMed

29. Jollow, DJ, Mitchell, JR, Zampaglione, N, Gillette, JR. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 1974;11:151–69. https://doi.org/10.1159/000136485.Search in Google Scholar PubMed

30. Coimbra-Costa, D, Alva, N, Duran, M, Carbonell, T, Rama, R. Oxidative stress and apoptosis after acute respiratory hypoxia and reoxygenation in rat brain. Redox Biol 2017;12:216–25. https://doi.org/10.1016/j.redox.2017.02.014.Search in Google Scholar PubMed PubMed Central

31. Krawisz, JE, Sharon, P, Stenson, WF. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity: assessment of inflammation in rat and hamster models. Gastroenterology 1984;87:1344–50. https://doi.org/10.1016/0016-5085(84)90202-6.Search in Google Scholar

32. Zhang, C, Tang, P, Xu, H, Weng, Y, Tang, Q, Zhao, H. Analysis of short-chain fatty acids in fecal samples by headspace-gas chromatography. Chromatographia 2018;81:1317–23. https://doi.org/10.1007/s10337-018-3572-7.Search in Google Scholar

33. Liguori, I, Russo, G, Curcio, F, Bulli, G, Aran, L, Della-Morte, D, et al.. Oxidative stress, aging, and diseases. Clin Interventions Aging 2018;13:757. https://doi.org/10.2147/cia.s158513.Search in Google Scholar PubMed PubMed Central

34. Kim, GH, Kim, JE, Rhie, SJ, Yoon, S. The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol 2015;24:325. https://doi.org/10.5607/en.2015.24.4.325.Search in Google Scholar PubMed PubMed Central

35. Bhat, AH, Dar, KB, Anees, S, Zargar, MA, Masood, A, Sofi, MA, et al.. Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother 2015;74:101–10. https://doi.org/10.1016/j.biopha.2015.07.025.Search in Google Scholar PubMed

36. Mutlu, EA, Gillevet, PM, Rangwala, H, Sikaroodi, M, Naqvi, A, Engen, PA, et al.. Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol 2012;302:G966–78. https://doi.org/10.1152/ajpgi.00380.2011.Search in Google Scholar PubMed PubMed Central

37. Barnes, MA, Roychowdhury, S, Nagy, LE. Innate immunity and cell death in alcoholic liver disease: role of cytochrome P4502E1. Redox Biol 2014;2:929–35. https://doi.org/10.1016/j.redox.2014.07.007.Search in Google Scholar PubMed PubMed Central

38. Ramachandra, CJ, Ja, KM, Chua, J, Cong, S, Shim, W, Hausenloy, DJ. Myeloperoxidase as a multifaceted target for cardiovascular protection. Antioxid Redox Signal 2020;32:1135–49. https://doi.org/10.1089/ars.2019.7971.Search in Google Scholar PubMed

39. Chami, B, Martin, NJ, Dennis, JM, Witting, PK. Myeloperoxidase in the inflamed colon: a novel target for treating inflammatory bowel disease. Arch Biochem Biophys 2018;645:61–71. https://doi.org/10.1016/j.abb.2018.03.012.Search in Google Scholar PubMed

40. Roth Flach, RJ, Su, C, Bollinger, E, Cortes, C, Robertson, AW, Opsahl, AC, et al.. Myeloperoxidase inhibition in mice alters atherosclerotic lesion composition. PLoS One 2019;14:e0214150. https://doi.org/10.1371/journal.pone.0214150.Search in Google Scholar PubMed PubMed Central

41. Sugamata, R, Dobashi, H, Nagao, T, Yamamoto, KI, Nakajima, N, Sato, Y, et al.. Contribution of neutrophil-derived myeloperoxidase in the early phase of fulminant acute respiratory distress syndrome induced by influenza virus infection. Microbiol Immunol 2012;56:171–82. https://doi.org/10.1111/j.1348-0421.2011.00424.x.Search in Google Scholar PubMed

42. McLoughlin, RF, Berthon, BS, Jensen, ME, Baines, KJ, Wood, LG. Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis. Am J Clin Nutr 2017;106:930–45. https://doi.org/10.3945/ajcn.117.156265.Search in Google Scholar PubMed

43. Cresci, GA, Bush, K, Nagy, LE. Tributyrin supplementation protects mice from acute ethanol-induced gut injury. Alcohol Clin Exp Res 2014;38:1489–501. https://doi.org/10.1111/acer.12428.Search in Google Scholar PubMed PubMed Central

44. Chen, S, Chen, H, Du, Q, Shen, J. Targeting myeloperoxidase (MPO) mediated oxidative stress and inflammation for reducing brain ischemia injury: potential application of natural compounds. Front Physiol 2020;11:433. https://doi.org/10.3389/fphys.2020.00433.Search in Google Scholar PubMed PubMed Central

45. Khan, AA, Alsahli, MA, Rahmani, AH. Myeloperoxidase as an active disease biomarker: recent biochemical and pathological perspectives. Med Sci 2018;6:33. https://doi.org/10.3390/medsci6020033.Search in Google Scholar PubMed PubMed Central

46. Sproston, NR, Ashworth, JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018;9:754. https://doi.org/10.3389/fimmu.2018.00754.Search in Google Scholar PubMed PubMed Central

47. Du Clos, TW, Mold, C. C-reactive protein: an activator of innate immunity and a modulator of adaptive immunity. Immunol Res 2004;30:261–77. https://doi.org/10.1385/ir:30:3:261.10.1385/IR:30:3:261Search in Google Scholar PubMed

48. Uddin, M, Hossain, MS, Rahman, M, Uddin, AH, Bhuiyan, M. Elemental zinc is inversely associated with C-reactive protein and oxidative stress in chronic liver disease. Biol Trace Elem Res 2017;178:189–93. https://doi.org/10.1007/s12011-016-0919-5.Search in Google Scholar PubMed

49. Baumeister, D, Akhtar, R, Ciufolini, S, Pariante, CM, Mondelli, V. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Mol Psychiatry 2016;21:642–9. https://doi.org/10.1038/mp.2015.67.Search in Google Scholar PubMed PubMed Central

50. Baruah, M. C-reactive protein (CRP) and markers of oxidative stress in acute myocardial infarction. In: Ansar, W, Ghosh, S, editors. Clinical Significance of C-reactive Protein. Singapore: Springer Nature; 2020:95–115 pp.10.1007/978-981-15-6787-2_4Search in Google Scholar

51. Irwin, A. The dark side of light: how artificial lighting is harming the natural world. Nature 2018;553:268–71. https://doi.org/10.1038/d41586-018-00665-7.Search in Google Scholar PubMed

52. Cardia, GF, Silva-Filho, SE, Silva, EL, Uchida, NS, Cavalcante, HA, Cassarotti, LL, et al.. Effect of lavender (Lavandula angustifolia) essential oil on acute inflammatory response. Evidence-Based Complementary Altern Med 2018. https://doi.org/10.1155/2018/1413940. 29743918.Search in Google Scholar PubMed PubMed Central

53. Ponferrada, Á, Caso, JR, Alou, L, Colón, A, Sevillano, D, Moro, MA, et al.. The role of PPARγ on restoration of colonic homeostasis after experimental stress-induced inflammation and dysfunction. Gastroenterology 2007;132:1791–803. https://doi.org/10.1053/j.gastro.2007.02.032.Search in Google Scholar PubMed

54. Chambers, ES, Morrison, DJ, Frost, G. Control of appetite and energy intake by SCFA: what are the potential underlying mechanisms? Proc Nutr Soc 2015;74:328–36. https://doi.org/10.1017/s0029665114001657.Search in Google Scholar PubMed

55. Hu, J, Lin, S, Zheng, B, Cheung, PC. Short-chain fatty acids in control of energy metabolism. Crit Rev Food Sci Nutr 2018;58:1243–9. https://doi.org/10.1080/10408398.2016.1245650.Search in Google Scholar PubMed

56. Wang, J, Ji, H, Wang, S, Liu, H, Zhang, W, Zhang, D, et al.. Probiotic Lactobacillus plantarum promotes intestinal barrier function by strengthening the epithelium and modulating gut microbiota. Front Microbiol 2018;9:1953. https://doi.org/10.3389/fmicb.2018.01953.Search in Google Scholar PubMed PubMed Central

57. Nielsen, TS, Jensen, BB, Purup, S, Jackson, S, Saarinen, M, Lyra, A, et al.. A search for synbiotics: effects of enzymatically modified arabinoxylan and Butyrivibrio fibrisolvens on short-chain fatty acids in the cecum content and plasma of rats. Food Funct 2016;7:1839–48. https://doi.org/10.1039/c6fo00114a.Search in Google Scholar PubMed

58. Li, X, Akhtar, S, Choudhry, MA. Alteration in intestine tight junction protein phosphorylation and apoptosis is associated with increase in IL-18 levels following alcohol intoxication and burn injury. Biochim Biophys Acta 2012;1822:196–203. https://doi.org/10.1016/j.bbadis.2011.09.019.Search in Google Scholar PubMed PubMed Central

59. Chaudhry, KK, Samak, G, Shukla, PK, Mir, H, Gangwar, R, Manda, B, et al.. ALDH2 deficiency promotes ethanol-induced gut barrier dysfunction and fatty liver in mice. Alcohol Clin Exp Res 2015;39:1465–75. https://doi.org/10.1111/acer.12777.Search in Google Scholar PubMed PubMed Central

60. Mir, H, Meena, AS, Chaudhry, KK, Shukla, PK, Gangwar, R, Manda, B, et al.. Occludin deficiency promotes ethanol-induced disruption of colonic epithelial junctions, gut barrier dysfunction and liver damage in mice. Biochim Biophys Acta 2016;1860:765–74. https://doi.org/10.1016/j.bbagen.2015.12.013.Search in Google Scholar PubMed PubMed Central


Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/jcim-2022-0353).


Received: 2022-09-29
Accepted: 2022-11-29
Published Online: 2022-12-21

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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