The gastrointestinal tract microbiome, probiotics, and mood

Abstract

Mental health is closely linked to physical health. Depression (e.g., major depression) is highly prevalent worldwide and a major cause of disability. In a subgroup with treatment-resistant depression, standard pharmacotherapy interventions provide small if any incremental improvement in patient outcomes and may also require the application of an alternate approach. Therefore, in addition to the standard pharmacotherapies prescribed, patients will also be advised on the benefits of psychological counseling, electroconvulsive therapy, and transcranial magnetic stimulation or increasing physical activity and reducing harmful substance consumption. Numerous nutraceuticals have a beneficial role in treatment-resistant depression and include, herbal medicines of which Hypericum perforatum is the best studied, omega-3 fatty acid preparations, S-Adenosyl-L-Methionine (SAMe), various mineral formulations (e.g., magnesium) and folate (singly or in combination with B group vitamins) are prescribed to a lesser extent. Furthermore, a largely neglected area of research activity has been the role of live probiotic cultures that contribute to repairing dysbiosis (a leaky gut barrier abnormality) in the gastrointestinal tract (GIT). In this commentary, we build a hypothesis that in addition suggests that GIT metabolites that are elaborated by the microbiome cohort may provide novel and significant avenues for efficacious therapeutic interventions for mood disorders. We posit that the microbiome in the gastrointestinal tract is implicit as an important participant for the amelioration of adverse mood conditions via the diverse metabolic activities provided by live beneficial bacteria (probiotics) as an active adjuvant treatment. This activity is in part triggered by a controlled release of reactive oxygen species (ROS) and hence further questions the antioxidant/oxidative stress postulate.

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References

  1. Amalaradjou MA, Bhunia AK (2012) Modern approaches in probiotics research to control foodborne pathogens. Adv Food Nutr Res 67:185–239

    CAS  PubMed  Article  Google Scholar 

  2. Andrews G, Hall W, Teeson M, Henderson S (1999) The mental health of Australians. Commonwealth Department of Health and Aged Care, Canberra

    Google Scholar 

  3. Benton D, Williams C, Brown A (2007) Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr 61:355–361

    CAS  PubMed  Article  Google Scholar 

  4. Berk M, Williams LJ, Jacka FN et al (2013) So depression is an inflammatory disease, but where does the inflammation come from? BMC Med 11:200

    PubMed Central  PubMed  Google Scholar 

  5. Black DW, Bell S, Hulbert J, Nasrallah A (1988) The importance of axis II diagnoses in patients with major depression. J Affect Disord 14:115–122

    CAS  PubMed  Article  Google Scholar 

  6. Bravo JA, Forsythe P, Chew MV et al (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. PNAS 108:16050–16055

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  7. Brophy JJ (1994) Personality disorder, symptoms and dexamethasone suppression in depression. Affect Disord 31:19–27

    CAS  Article  Google Scholar 

  8. Calanni F, Renzulli C, Barbanti M, Viscomi GC (2014) Rifaximin: beyond the traditional antibiotic activity. J Antibiot (Tokyo). doi: 10.1038/ja.2014.106

  9. Clarke G, Grenham S, Scully P et al (2013) The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18(6):666–673

    CAS  PubMed  Article  Google Scholar 

  10. Collins SM, Bercik P (2009) The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 136:2003–2014

    PubMed  Article  Google Scholar 

  11. Cotter PD, Stanton C, Ross RP, Hill C (2012) The impact of antibiotics on the gut microbiota as revealed by high throughput DNA sequencing. Discov Med 13(70):193–199

    PubMed  Google Scholar 

  12. Cryan JF, O’Mahony SM (2011) The microbiome-gut-brain axis: from bowel to behavior. Neurogastroenterol Motil 23:187–192

    CAS  PubMed  Article  Google Scholar 

  13. Dinan TG, Cryan JF (2013) Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol Motil 25:713–719

    CAS  PubMed  Article  Google Scholar 

  14. Dinan TG, Stanton C, Cryan JF (2013) Psychobiotics: a novel class of psychotropic. Biol Psychiatry 74(10):720–726

    CAS  PubMed  Article  Google Scholar 

  15. Fava M (2010) Switching treatments for complicated depression. J Clin Psychiatry 71(2):e04

    PubMed  Article  Google Scholar 

  16. Foster JA, McVey Neufeld KA (2013) Gut–brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 36(5):305–312

    CAS  PubMed  Article  Google Scholar 

  17. Furness JB, Rivera LR, Cho HJ et al (2013) The gut as a sensory organ. Nat Rev Gastroenterol Hepatol 10(12):729–740

    CAS  PubMed  Article  Google Scholar 

  18. Halmos EP, Christophersen CT, Bird AR et al (2014) Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. doi: 10.1136/gutjnl-2014-307264

  19. Hungin AP, Mulligan C, Pot B et al (2013) Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice—an evidence-based international guide. Aliment Pharmacol Ther 38(8):864–886

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  20. Katon W, Russo J, Von Korff M et al (2002) Long-term effects of a collaborative care intervention in persistently depressed primary care patients. J Gen Intern Med 17(10):741–748

    PubMed Central  PubMed  Article  Google Scholar 

  21. Kiloh LG, Andrews G, Neilson M (1988) The long term outcomes of depression. Br J Psychiatry 153:752–759

    CAS  PubMed  Article  Google Scholar 

  22. Lee AS, Murray RM (1988) The long-term outcome of Maudsley depressives. Br J Psychiatry 153:741–751

    CAS  PubMed  Article  Google Scholar 

  23. Loenen W (2006) S-adenosylmethionine: Jack of all trades and master of everything? Biochem Soc Trans 34(Pt 2):330–333

    CAS  PubMed  Google Scholar 

  24. Lyte M (2011) Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics. BioEssays 33:574–581

    CAS  PubMed  Article  Google Scholar 

  25. Maes M, Kubera M, Leunis JC et al (2013) In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS-damaged neoepitopes. Acta Psychiatr Scand 127(5):344–354

    CAS  PubMed  Article  Google Scholar 

  26. Messaoudi M, Lalonde R, Violle N et al (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 105:755–764

    CAS  PubMed  Article  Google Scholar 

  27. Morris KV, Mattick JS (2014) The rise of regulatory RNA. Nat Rev Genet 15(6):423–437

    CAS  PubMed  Article  Google Scholar 

  28. Najm WI, Reinsch S, Hoehler F et al (2004) S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. ISRCTN36233495. BMC Musculoskelet Disord 5:6

    PubMed Central  PubMed  Article  Google Scholar 

  29. National Collaborating Centre for Mental Health (UK) (2010) Leicester (UK): British Psychological Society. National Institute for Health and Clinical Excellence: Guidance. Depression: the treatment and management of depression in adults (Updated Edition)

  30. Naviaux RK (2014) Metabolic features of the cell danger response. Mitochondrion 16:7–17

    CAS  PubMed  Article  Google Scholar 

  31. Neish AS (2013) Redox signaling mediated by the gut microbiota. Free Radic Res 13 [Epub ahead of print]

  32. Nestler EJ, Barrot M, DiLeone RJ et al (2002) Neurobiology of depression. Neuron 34(1):13–25

    CAS  PubMed  Article  Google Scholar 

  33. Papakostas GI, Mischoulon D, Shyu I et al (2010) S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry 167(8):942–949

    PubMed  Article  Google Scholar 

  34. Perovic B, Jovanovic M, Miljkovic B, Vezmar S (2010) Getting the balance right: established and emerging therapies for major depressive disorders. Nuropsychiatr Dis Treat 7(6):343–364

    Google Scholar 

  35. Piccinelli M, Wilkingson G (1994) Outcome of depression in psychiatric settings. Br J Psychiatry 164:297–304

    CAS  PubMed  Article  Google Scholar 

  36. Rao AV, Bested AC, Beaulne TM et al (2009) A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog 1:6

    PubMed Central  PubMed  Article  Google Scholar 

  37. Roshchina VV (2010) Evolutionary considerations of neurotransmitters in microbial, plant, and animal cells. In: Lyte M, Freestone PPE (eds) Microbial endocrinology: interkingdom signaling in infectious disease and health. Springer, New York, pp 17–52

    Google Scholar 

  38. Schousboe A, Waagepetersen HS (2007) GABA: homeostatic and pharmacological aspects. In: Tepper JM, Abercrombie ED, Bolam JP (eds) GABA and the basal ganglia: from molecules to systems, vol 919. Elsevier Science B, Amsterdam

    Google Scholar 

  39. Shea TM, Glass DR, Pilkonis PA et al (1987) Personality disorders and treatment outcome in the NIMH Treatment of Depression Collaborative Research Program. J Personal Disord 1:27–42

    Article  Google Scholar 

  40. Staudacher H, Lomer MCE, Anderson J et al (2012) Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome. J Nutr 142:1510–1518

    CAS  PubMed  Article  Google Scholar 

  41. Tan M, Zhu JC, Du J et al (2011) Effects of probiotics on serum levels of Th1/Th2 cytokine and clinical outcomes in severe traumatic brain-injured patients: a prospective randomized pilot study. Crit Care 15:R290

    PubMed Central  PubMed  Article  Google Scholar 

  42. Tillisch K, Labus J, Kilpatrick L et al (2013) Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144:1394–1401 1401 e1391-1394

    CAS  PubMed  Article  Google Scholar 

  43. Timmerman HM, Koning CJ, Mulder L et al (2004) Monostrain, multistrain and multispecies probiotics—a comparison of functionality and efficacy. Int J Food Microbiol 96:219–233

    CAS  PubMed  Article  Google Scholar 

  44. Vitetta L, Anton B, Cortizo F, Sali A (2005) Mind-body medicine: stress and its impact on overall health and longevity. Ann NY Acad Sci 1057:492–505

    CAS  PubMed  Article  Google Scholar 

  45. Vitetta L, Briskey D, Hayes E et al (2012) A review of the pharmacobiotic regulation of gastrointestinal inflammation by probiotics, commensal bacteria and prebiotics. Inflammopharmacology 20:251–266

    CAS  PubMed  Article  Google Scholar 

  46. Vitetta L, Linnane AW, Gobe GC (2013a) From the gastrointestinal tract (GIT) to the kidneys: live bacterial cultures (probiotics) mediating reductions of uremic toxin levels via free radical signaling. Toxins (Basel) 5(11):2042–2057

    CAS  Article  Google Scholar 

  47. Vitetta L, Couslon S, Linnane AW, Butt H (2013b) The gastrointestinal microbiome and musculoskeletal diseases: is there a role for probiotics and prebiotics? Pathogens 2:606–626

    CAS  Article  Google Scholar 

  48. Waters LS, Storz G (2009) Regulatory RNAs in bacteria. Cell 136(4):615–628

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  49. WHO (2012) World Health Organisation, depression burden of disease. http://www.who.int/mediacentre/factsheets/fs369/en/. Accessed August 2014

  50. Yang X, Xie L, Li Y, Wei C (2009) More than 9,000,000 unique genes in human gut bacterial community: estimating gene numbers inside a human body. PLoS One 4:e6074

    PubMed Central  PubMed  Article  Google Scholar 

  51. Zoetendal EG, Rajilic-Stojanovic M, de Vos WM (2008) High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut 57:1605–1615

    CAS  PubMed  Article  Google Scholar 

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Acknowledgments

Luis Vitetta has received National Institute of Complementary Medicine and National Health and Medical Research Council of Australia competitive funding and Industry support for research into nutraceuticals.

Conflict of interest

The authors have no further conflicts of interest relevant to the content of this review.

Author contributions

LV and MB conception and design of commentary. LV, MB, and HA read, amended and approved the final version of the manuscript.

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Correspondence to Luis Vitetta.

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Vitetta, L., Bambling, M. & Alford, H. The gastrointestinal tract microbiome, probiotics, and mood. Inflammopharmacol 22, 333–339 (2014). https://doi.org/10.1007/s10787-014-0216-x

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Keywords

  • Mood
  • Depression
  • Nutraceuticals
  • Gastrointestinal tract
  • Microbiome
  • Dysbiosis
  • Probiotics
  • Prebiotics