Skip to main content Accessibility help

Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects

  • Michaël Messaoudi (a1), Robert Lalonde (a2), Nicolas Violle (a1), Hervé Javelot (a3), Didier Desor (a4), Amine Nejdi (a1), Jean-François Bisson (a1), Catherine Rougeot (a5), Matthieu Pichelin (a6), Murielle Cazaubiel (a6) and Jean-Marc Cazaubiel (a6)...


In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger–hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects
      Available formats


Corresponding author

*Corresponding author: M. Messaoudi, fax +33 383 446 441, email


Hide All
1Forsythe, P, Sudo, N, Dinan, T, et al. (2010) Mood and gut feelings. Brain Behav Immun 24, 916.
2Mayer, EA (2000) The neurobiology of stress and gastrointestinal disease. Gut 47, 861869.
3McEwen, BS (2003) Mood disorders and allostatic load. Biol Psychiatry 54, 200207.
4O'Mahony, SM, Marchesi, JR, Scully, P, et al. (2009) Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 65, 263267.
5Lutgendorff, F, Akkermans, LM & Söderholm, JD (2008) The role of microbiota and probiotics in stress-induced gastro-intestinal damage. Curr Mol Med 8, 282298.
6Drossman, DA, Sandler, RS & McKee, DC (1982) Bowel patterns among subjects not seeking health care. Gastroenterology 83, 529534.
7Whitehead, WE, Crowell, MD, Robinson, JC, et al. (1992) Effects of stressful life events on bowel symptoms: subjects with irritable bowel syndrome compared with subjects without bowel dysfunction. Gut 33, 825830.
8Gwee, KA (1999) The role of psychological and biological factors in post-infective gut dysfunction. Gut 44, 400406.
9Duffy, LC, Zielezny, MA, Marshall, JR, et al. (1991) Relevance of major stress events as an indicator of disease activity prevalence in inflammatory bowel disease. Behav Med 17, 101110.
10Garrett, VD, Brantley, PJ, Jones, G, et al. (1991) The relationship between daily stress and Crohn's disease. J Behav Med 14, 8796.
11Greene, B & Blanchard, EB (1994) Cognitive therapy for irritable bowel syndrome. J Consult Clin Psychol 62, 576582.
12Bennett, EJ, Tennant, CC, Piesse, C, et al. (1998) Level of chronic life stress predicts clinical outcome in irritable bowel syndrome. Gut 43, 256261.
13Levenstein, S, Kaplan, GA & Smith, MW (1997) Psychological predictors of peptic ulcer incidence in the Alameda County Study. J Clin Gastroenterol 24, 140146.
14Levenstein, S, Ackerman, S, Kiecolt-Glaser, JK, et al. (1999) Stress and peptic ulcer disease. JAMA 281, 1011.
15Levenstein, S, Prantera, C, Varvo, V, et al. (2000) Stress and exacerbation in ulcerative colitis: a prospective study of patients enrolled in remission. Am J Gastroenterol 95, 12131220.
16Aoyama, N, Kinoshita, Y, Fujimoto, S, Himeno, S, et al. (1998) Peptic ulcers after the Hanshin-Awaji earthquake: increased incidence of bleeding gastric ulcers. Am J Gastroenterol 93, 311316.
17Finlay-Jones, R & Brown, GW (1981) Types of stressful life event and the onset of anxiety and depressive disorders. Psychol Med 11, 803815.
18Caspi, A, Sugden, K, Moffitt, TE, et al. (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386389.
19Kendler, KS, Prescott, CA, Myers, J, et al. (2003) The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Arch Gen Psychiatry 60, 929937.
20Wheatley, D (1998) Stress, anxiety and depression. Stress Med 13, 173177.
21Whitehead, WE, Palsson, O & Jones, KR (2002) Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology 122, 11401156.
22Graff, LA, Walker, JR & Bernstein, CN (2009) Depression and anxiety in inflammatory bowel disease: a review of comorbidity and management. Inflamm Bowel Dis 15, 11051118.
23Neufeld, KA & Foster, JA (2009) Effects of gut microbiota on the brain: implications for psychiatry. J Psychiatry Neurosci 34, 230231.
24Goehler, LE, Park, SM, Opitz, N, et al. (2007) Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior. Brain Behav Immun 22, 354366.
25Sudo, N, Chida, Y, Aiba, Y, et al. (2004) Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. J Physiol 558, 263275.
26Söderholm, JD, Yates, DA, Gareau, MG, et al. (2002) Neonatal maternal separation predisposes adult rats to colonic barrier dysfunction in response to mild stress. Am J Physiol Gastrointest Liver Physiol 283, G1257G1263.
27Coutinho, SV, Plotsky, PM, Sablad, M, et al. (2002) Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. Am J Physiol Gastrointest Liver Physiol 282, G307G316.
28Gareau, MG, Jury, J, MacQueen, G, et al. (2007) Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut 56, 15221528.
29Girard, SA, Bah, TM, Kaloustian, S, et al. (2009) Lactobacillus helveticus and Bifidobacterium longum in combination reduce the apoptosis propensity in the limbic system after myocardial infarction in a rat model. Br J Nutr 102, 14201425.
30Bailey, MT, Lubach, GR & Coe, CL (2004) Prenatal stress alters bacterial colonization of the gut in infant monkeys. J Pediatr Gastroenterol Nutr 38, 414421.
31Qin, J, Li, R, Raes, J, et al. (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 5965.
32Pineiro, M & Stanton, C (2007) Probiotic bacteria: legislative framework – requirements to evidence basis. J Nutr 137, 850S853S.
33Arvanitoyannis, IS & Van Houwelingen-Koukaliaroglou, M (2005) Functional foods: a survey of health claims, pros and cons, and current legislation. Crit Rev Food Sci Nutr 45, 385404.
34Diop, L, Guillou, S & Durand, H (2008) Probiotic food supplement reduces stress-induced gastrointestinal symptoms in volunteers: a double-blind, placebo-controlled, randomized trial. Nutr Res 28, 15.
35Estrada, A, Drew, MD & Van Kessel, A (2001) Effect of the dietary supplementation of fructooligosaccharides and Bifidobacterium longum to early-weaned pigs on performance and fecal bacterial populations. Can J Anim Sci 81, 141148.
36Wine, E, Gareau, MG, Johnson-Henry, K, et al. (2009) Strain-specific probiotic (Lactobacillus helveticus) inhibition of Campylobacter jejuni invasion of human intestinal epithelial cells. FEMS Microbiol Lett 300, 146152.
37Wallace, TD, Bradley, S, Buckley, ND, et al. (2003) Interactions of lactic acid bacteria with human intestinal epithelial cells: effects on cytokine production. J Food Prot 66, 466472.
38Haskey, N & Dahl, WJ (2009) Synbiotic therapy improves quality of life and reduced symptoms in pediatric ulcerative colitis. Infant Child Adoles Nutr 1, 8893.
39Yamamura, S, Morishima, H, Kumano-go, T, et al. (2009) The effect of Lactobacillus helveticus fermented milk on sleep and health perception in elderly subjects. Eur J Nutr 63, 100105.
40Treit, D, Pinel, JP & Fibiger, HC (1981) Conditioned defensive burying: a new paradigm for the study of anxiolytic agents. Pharmacol Biochem Behav 15, 619626.
41Messaoudi, M, Lalonde, R, Schroeder, H, et al. (2009) Anxiolytic-like effects and safety profile of a tryptic hydrolysate from bovine alpha s1-casein in rats. Fundam Clin Pharmacol 23, 323330.
42Derogatis, LR, Lipman, RS, Rickels, K, et al. (1974) The Hopkins Symptom Checklist (HSCL): a self-report symptom inventory. Behav Sci 19, 115.
43Derogatis, LR, Lipman, RS, Rickels, K, et al. (1974) The Hopkins Symptom Checklist (HSCL). A measure of primary symptom dimensions. Mod Probl Pharmacopsychiatry 7, 79110.
44Zigmond, AS & Snaith, RP (1983) The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 67, 361370.
45Cohen, S & Williamson, G (1988) Perceived stress in a probability sample of the United States. In The Social Psychology of Health: Claremont Symposium on Applied Social Psychology, pp. 3167 [Spacapan, S and Oskamp, S, editors]. Newbury Park, CA: Sage.
46Vitaliano, PP (1985) The Ways of Coping Checklist: revision and psychometric properties. Multiv Behav Res 20, 326.
47Paulhan, I, Nuissier, J, Quintard, B, et al. (1994) The measurement of “coping”. French translation and validation of the Vitaliano's scale (Vitaliano et al. 1985). Ann Med Psychol (Paris) 152, 292299.
48Mason, JW, Giller, EL, Kosten, TR, et al. (1986) Urinary free-cortisol levels in posttraumatic stress disorder patients. J Nerv Ment Dis 174, 145149.
49Martin, FP, Rezzi, S, Peré-Trepat, E, et al. (2009) Metabolic effects of dark chocolate consumption on energy, gut microbiota, and stress-related metabolism in free-living subjects. J Proteome Res 8, 55685579.
50ASAB/ABS (2006) Guidelines for the treatment of animals in behavioural research and teaching. Anim Behav 71, 245253.
51Canadian Council on Animal Care (1993) Guide to the Care and Use of Experimental Animals, vol. 1, 2nd ed. Ottawa, ON: CCAC.
52Naser, SM, Hagen, KE, Vancanneyt, M, et al. (2006) Lactobacillus suntoryeus Cachat and Priest 2005 is a later synonym of Lactobacillus helveticus (Orla-Jensen 1919) Bergey et al. 1925 (approved lists 1980). Int J Syst Evol Microbiol 56, 355360.
53Hagen, KE, Tramp, CA, Altermann, E, et al. (2010) Sequence analysis of plasmid pIR52-1 from Lactobacillus helveticus R0052 and investigation of its origin of replication. Plasmid 63, 108117.
54Ventura, M, Callegari, ML, Morelli, L, et al. (2000) S-layer gene as a molecular marker for identification of Lactobacillus helveticus. FEMS Microbiol Lett 189, 275279.
55Ventura, M, Canchaya, C, Meylan, V, et al. (2003) Analysis, characterization, and loci of the tuf genes in Lactobacillus and Bifidobacterium species and their direct application for species identification. Appl Environ Microbiol 69, 69086922.
56Altschul, SF, Madden, TL, Schaffer, AA, et al. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25, 33893402.
57Bjelland, I, Dahl, AA & Haug, TT (2002) The validity of the Hospital Anxiety and Depression Scale. An updated literature review. Psychosom Res 52, 6977.
58Lazarus, RS & Folkman, S (1984) Stress, Appraisal and Coping. New York: Springer.
59Benton, D, Williams, C & Brown, A (2007) Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Nutr 61, 355361.
60Rao, 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 Pathogens 1, 16.
61Yan, F & Polk, DB (2002) Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. J Biol Chem 277, 5095950965.
62Lammers, KM, Brigidi, P, Vitali, B, et al. (2003) Immunomodulatory effects of probiotic bacteria DNA: IL-1 and IL-10 response in human peripheral blood mononuclear cells. FEMS Immunol Med Microbiol 38, 165172.
63Ramiah, K, van Reenen, CA & Dicks, LM (2008) Surface-bound proteins of Lactobacillus plantarum 423 that contribute to adhesion of Caco-2 cells and their role in competitive exclusion and displacement of Clostridium sporogenes and Enterococcus faecalis. Res Microbiol 159, 470475.
64Parracho, H, McCartney, AL & Gibson, GR (2005) Probiotics and prebiotics in infant nutrition. Proc Nutr Soc 66, 405411.
65Hanstock, TL, Clayton, EH, Li, KM, et al. (2004) Anxiety and aggression associated with the fermentation of carbohydrates in the hindgut of rats. Physiol Behav 82, 357368.
66Shultz, SR, MacFabe, DF, Ossenkopp, KP, et al. (2008) Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: implications for an animal model of autism. Neuropharmacology 54, 901911.
67Alesci, S, Martinez, PE, Kelkar, S, et al. (2005) Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: clinical implications. J Clin Endocrinol Metab 90, 25222530.
68Capuron, L, Neurauter, G, Musselman, DL, et al. (2003) Interferon-alpha-induced changes in tryptophan metabolism. Relationship to depression and paroxetine treatment. Biol Psychiatry 54, 906914.
69Hauser, P, Khosla, J, Aurora, H, et al. (2002) A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorder in patients with hepatitis C. Mol Psychiatry 7, 942947.
70Musselman, DL, Lawson, DH, Gumnick, JF, et al. (2001) Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med 344, 961966.
71Maes, M (2001) The immunoregulatory effects of antidepressants. Hum Psychopharmacol 16, 95103.
72Desbonnet, L, Garrett, L, Clarke, G, et al. (2008) The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res 43, 164174.
73Duncker, SC, Wang, L, Hols, P, et al. (2008) The d-alanine content of lipoteichoic acid is crucial for Lactobacillus plantarum-mediated protection from visceral pain perception in a rat colorectal distension model. Neurogastroenterol Motil 20, 843850.
74Karimi, K, Inman, MD, Bienenstock, J, et al. (2009) Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice. Am J Respir Crit Care Med 179, 186193.
75Logan, AC & Katzman, M (2005) Major depressive disorder: probiotics may be an adjuvant therapy. Med Hypotheses 64, 533538.
76Munck, A, Guyre, PM & Holbrook, NJ (1984) Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 5, 2544.
77Ottenweller, JE, Natelson, BH, Pitman, DL, et al. (1989) Adrenocortical and behavioral responses to repeated stressors: toward an animal model of chronic stress and stress-related mental illness. Biol Psychiatry 26, 829841.
78Lowry, CA, Hollis, JH, de Vries, A, et al. (2007) Identification of an immune-responsive mesolimbocortical serotonergic system: potential role in regulation of emotional behavior. Neuroscience 146, 756772.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed