Molecular Neurobiology

, Volume 55, Issue 6, pp 5337–5352 | Cite as

Bifidobacterium pseudocatenulatum CECT 7765 Ameliorates Neuroendocrine Alterations Associated with an Exaggerated Stress Response and Anhedonia in Obese Mice

  • Ana AgustiEmail author
  • A. Moya-Pérez
  • I. Campillo
  • S. Montserrat-de la Paz
  • V. Cerrudo
  • A. Perez-Villalba
  • Yolanda SanzEmail author


Obesity, besides being a problem of metabolic dysfunction, constitutes a risk factor for psychological disorders. Experimental models of diet-induced obesity have revealed that obese animals are prone to anxious and depressive-like behaviors. The present study aimed to evaluate whether Bifidobacterium pseudocatenulatum CECT 7765 could reverse the neurobehavioral consequences of obesity in a high-fat diet (HFD) fed mouse model via regulation of the gut–brain axis. Adult male wild-type C57BL-6 mice were fed a standard diet or HFD, supplemented with either placebo or the bifidobacterial strain for 13 weeks. Behavioral tests were performed, and immune and neuroendocrine parameters were analyzed including leptin and corticosterone and their receptors, Toll-like receptor 2 (TLR2) and neurotransmitters. We found that obese mice showed anhedonia (p < 0.050) indicative of a depressive-like behavior and an exaggerated hypothalamic-pituitary axis (HPA)-mediated stress response to acute physical (p < 0.001) and social stress (p < 0.050), but these alterations were ameliorated by B. pseudocatenulatum CECT 7765 (p < 0.050). These behavioral effects were parallel to reductions of the obesity-associated hyperleptinemia (p < 0.001) and restoration of leptin signaling (p < 0.050), along with fat mass loss (p < 0.010). B. pseudocatenulatum CECT 7765 administration also led to restoration of the obesity-induced reductions in adrenaline in the hypothalamus (p < 0.010), involved in the hypothalamic control of energy balance. Furthermore, the bifidobacterial strain reduced the obesity-induced upregulation of TLR2 protein or gene expression in the intestine (p < 0.010) and the hippocampus (p < 0.050) and restored the alterations of 5-HT levels in the hippocampus (p < 0.050), which could contribute to attenuating the obesity-associated depressive-like behavior (p < 0.050). In summary, the results indicate that B. pseudocatenulatum CECT 7765 could play a role in depressive behavior comorbid with obesity via regulation of endocrine and immune mediators of the gut–brain axis.


Obesity Bifidobacterium Microbiota Depression Stress Serotonin TLR2 


Funding Information

This work and the contract of AA were supported by grant AGL2014-52101-P from the Spanish Ministry of Economy and Competitiveness (MINECO). The scholarship of AM from MECD and the PTA contract of IC from MINECO are also fully acknowledged. CIBERNED funding AP is also acknowledged.

Compliance with Ethical Standards

Experiments were carried out in strict compliance with the recommendations provided in the Guide for the Care and Use of Laboratory Animals of the University of Valencia (Central Service of Support to Research [SCSIE], University of Valencia, Spain), and the protocol was approved by its Ethics Committee (Approval number 2015/VSC/PEA/00041).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2017_768_MOESM1_ESM.docx (14 kb)
Supplemental Table 1 (DOCX 14 kb)


  1. 1.
    Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG (2010) Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry 67(3):220–229CrossRefPubMedGoogle Scholar
  2. 2.
    Needham BL, Epel ES, Adler NE, Kiefe C (2010) Trajectories of change in obesity and symptoms of depression: the Cardia study. Am J Public Health 100(6):1040–1046CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ma J, Xiao L (2010) Obesity and depression in US women: results from the 2005-2006 National Health and Nutritional Examination Survey. Obesity (Silver Spring) 18(2):347–353CrossRefGoogle Scholar
  4. 4.
    Farshim P, Walton G, Chakrabarti B, Givens I, Saddy D, Kitchen I, Swann J R, Bailey A (2016) Maternal weaning modulates emotional behavior and regulates the gut-brain axis. Sci Rep 6:21958CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Morris G, Berk M, Carvalho A, Caso JR, Sanz Y, Walder K, Maes M (2016) The role of the microbial metabolites including tryptophan catabolites and short chain fatty acids in the pathophysiology of immune-inflammatory and neuroimmune disease. Mol Neurobiol 54(6):4432–4451Google Scholar
  6. 6.
    Sharma S, Fulton S (2013) Diet-induced obesity promotes depressive-like behaviour that is associated with neural adaptations in brain reward circuitry. Int J Obes 37(3):382–389CrossRefGoogle Scholar
  7. 7.
    Pan A, Sun Q, Czernichow S, Kivimaki M, Okereke OI, Lucas M, Manson JE, Ascherio A et al (2012) Bidirectional association between depression and obesity in middle-aged and older women. Int J Obes 36(4):595–602CrossRefGoogle Scholar
  8. 8.
    Cooke AA, Connaughton RM, Lyons CL, McMorrow AM, Roche HM (2016) Fatty acids and chronic low grade inflammation associated with obesity and the metabolic syndrome. Eur J Pharmacol 785:207–214CrossRefPubMedGoogle Scholar
  9. 9.
    Sanz Y, Moya-Perez A (2014) Microbiota, inflammation and obesity. Adv Exp Med Biol 817:291–317CrossRefPubMedGoogle Scholar
  10. 10.
    Latorre E, Layunta E, Grasa L, Castro M, Pardo J, Gomollon F, Alcalde AI, Mesonero JE (2016) Intestinal serotonin transporter inhibition by Toll-like receptor 2 activation. A feedback modulation. PLoS One 11(12):e0169303CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Himes RW, Smith CW (2010) Tlr2 is critical for diet-induced metabolic syndrome in a murine model. FASEB J 24(3):731–739CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Mawe GM, Hoffman JM (2013) Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol 10(8):473–486CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Spiller R (2008) Serotonin and Gi clinical disorders. Neuropharmacology 55(6):1072–1080CrossRefPubMedGoogle Scholar
  14. 14.
    Dale E, Pehrson AL, Jeyarajah T, Li Y, Leiser SC, Smagin G, Olsen CK, Sanchez C (2016) Effects of serotonin in the hippocampus: how SSRIs and multimodal antidepressants might regulate pyramidal cell function. CNS Spectr 21(2):143–161CrossRefPubMedGoogle Scholar
  15. 15.
    Yamada N, Katsuura G, Ochi Y, Ebihara K, Kusakabe T, Hosoda K, Nakao K (2011) Impaired CNS leptin action is implicated in depression associated with obesity. Endocrinology 152(7):2634–2643CrossRefPubMedGoogle Scholar
  16. 16.
    Collins SM, Surette M, Bercik P (2012) The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 10:735–742CrossRefPubMedGoogle Scholar
  17. 17.
    De Palma G, Blennerhassett P, Lu J, Deng Y, Park AJ, Green W, Denou E, Silva MA et al (2015) Microbiota and host determinants of behavioral phenotype in maternally separated mice. Nat Commun 6:7735CrossRefPubMedGoogle Scholar
  18. 18.
    Sanz Y (2016) The encyclopedia of food and health. Academic Press, OxfordGoogle Scholar
  19. 19.
    Hanstock TL, Mallet PE, Clayton EH (2010) Increased plasma D-lactic acid associated with impaired memory in rats. Physiol Behav 101(5):653–659CrossRefPubMedGoogle Scholar
  20. 20.
    Tana C, Umesaki Y, Imaoka A, Handa T, Kanazawa M, Fukudo S (2010) Neurogastroenterol Motil. Neurogastroenterol Motil 22(5):512–519PubMedGoogle Scholar
  21. 21.
    Schroeder FA, Lin CL, Crusio WE, Akbarian S (2007) Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol Psychiatry 62(1):55–64CrossRefPubMedGoogle Scholar
  22. 22.
    Logan AC, Katzman M (2005) Major depressive disorder: probiotics may be an adjuvant therapy. Med Hypotheses 64(3):533–538CrossRefPubMedGoogle Scholar
  23. 23.
    Shadnoush M, Shaker Hosseini R, Mehrabi Y, Delpisheh A, Alipoor E, Faghfoori Z, Mohammadpour N, Zaringhalam Moghadam J (2013) Probiotic yogurt affects pro- and anti-inflammatory factors in patients with inflammatory bowel disease. Iran J Pharm Res 12(4):929–936PubMedPubMedCentralGoogle Scholar
  24. 24.
    Barouei J, Moussavi M, Hodgson DM (2015) Perinatal maternal probiotic intervention impacts immune responses and ileal mucin gene expression in a rat model of irritable bowel syndrome. Benefic Microbes 6(1):83–95CrossRefGoogle Scholar
  25. 25.
    Moya-Perez A, Neef A, Sanz Y (2015) Bifidobacterium pseudocatenulatum Cect 7765 reduces obesity-associated inflammation by restoring the lymphocyte-macrophage balance and gut microbiota structure in high-fat diet-fed mice. PLoS One 10(7):e0126976CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Moya-Perez A, Romo-Vaquero M, Tomas-Barberan F, Sanz Y, Garcia-Conesa MT (2014) Hepatic molecular responses to Bifidobacterium pseudocatenulatum Cect 7765 in a mouse model of diet-induced obesity. Nutr Metab Cardiovasc Dis 24(1):57–64CrossRefPubMedGoogle Scholar
  27. 27.
    Cano PG, Santacruz A, Trejo FM, Sanz Y (2013) Bifidobacterium Cect 7765 improves metabolic and immunological alterations associated with obesity in high-fat diet-fed mice. Obesity (Silver Spring) 21(11):2310–2321CrossRefGoogle Scholar
  28. 28.
    Moratalla A, Gomez-Hurtado I, Santacruz A, Moya A, Peiro G, Zapater P, Gonzalez-Navajas JM, Gimenez P et al (2014) Protective effect of Bifidobacterium pseudocatenulatum Cect7765 against induced bacterial antigen translocation in experimental cirrhosis. Liver Int 34(6):850–858CrossRefPubMedGoogle Scholar
  29. 29.
    Moratalla A, Caparros E, Juanola O, Portune K, Puig-Kroger A, Estrada-Capetillo L, Bellot P, Gomez-Hurtado I et al (2016) Bifidobacterium pseudocatenulatum Cect7765 induces an M2 anti-inflammatory transition in macrophages from patients with cirrhosis. J Hepatol 64(1):135–145CrossRefPubMedGoogle Scholar
  30. 30.
    Stetz J, Hunt K, Kendall KC, Wasser SK (2013) Effects of exposure, diet, and thermoregulation on fecal glucocorticoid measures in wild bears. PLoS One 8(2):e55967CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF et al (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161(2):264–276CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Duncko R, Brtko J, Kvetnansky R, Jezova D (2001) Altered function of peripheral organ systems in rats exposed to chronic mild stress model of depression. Cell Mol Neurobiol 21(4):403–411CrossRefPubMedGoogle Scholar
  33. 33.
    Crawley J, Goodwin FK (1980) Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav 13(2):167–170CrossRefPubMedGoogle Scholar
  34. 34.
    Liu J, Guo M, Lu XY (2015) Leptin/Leprb in the ventral tegmental area mediates anxiety-related behaviors. Int J Neuropsychopharmacol 19(2).
  35. 35.
    Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229(2):327–336PubMedGoogle Scholar
  36. 36.
    Mahanti S, Majhi A, Chongdar S, Kundu K, Dutta K, Basu A, Bishayi B (2013) Increased resistance of immobilized-stressed mice to infection: correlation with behavioral alterations. Brain Behav Immun 28:115–127CrossRefPubMedGoogle Scholar
  37. 37.
    Tamashiro KL, Nguyen MM, Sakai RR (2005) Social stress: from rodents to primates. Front Neuroendocrinol 26(1):27–40CrossRefPubMedGoogle Scholar
  38. 38.
    De Miguel Z, Vegas O, Garmendia L, Arregi A, Beitia G, Azpiroz A (2011) Behavioral coping strategies in response to social stress are associated with distinct neuroendocrine, monoaminergic and immune response profiles in mice. Behav Brain Res 225(2):554–561CrossRefPubMedGoogle Scholar
  39. 39.
    De Kloet ER, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6(6):463–475CrossRefPubMedGoogle Scholar
  40. 40.
    Wilkening JL, Ray C, Varner J (2016) When can we measure stress noninvasively? Postdeposition effects on a fecal stress metric confound a multiregional assessment. Ecol Evol 6(2):502–513CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Denenberg VH (1969) Open-field behavior in the rat: what does it mean? Ann N Y Acad Sci 159(3):852–859CrossRefPubMedGoogle Scholar
  42. 42.
    Seibenhener ML, Wooten MC (2015) Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp (96):e52434.
  43. 43.
    Hageman I, Nielsenb M, Wortweina G, Diemerc NH, Jorgensen MB (2009) Electroconvulsive stimulation normalize stress-induced changes in the glucocorticoid receptor and behaviour. Behav Brain Res 196(1):71–77CrossRefPubMedGoogle Scholar
  44. 44.
    Colelli V, Campus P, Conversi D, Orsini C, Cabib S (2014) Either the dorsal hippocampus or the dorsolateral striatum is selectively involved in consolidation of forced swim-induced immobility depending on genetic background. Neurobiol Learn Mem 111:49–55CrossRefPubMedGoogle Scholar
  45. 45.
    Castagne V, Moser P, Porsolt RD (2009) Behavioral assessment of antidepressant activity in rodents. In: Buccafusco JJ (ed) Methods of behavior analysis in neuroscience, 2nd edn. CRC Press, Boca RatonGoogle Scholar
  46. 46.
    Yang JL, Liu X, Jiang H, Pan F, Ho CS, Ho RC (2016) The effects of high-fat-diet combined with chronic unpredictable mild stress on depression-like behavior and leptin/Leprb in male rats. Sci Rep 6:35239CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Lopresti AL, Maker GL, Hood SD, Drummond PD (2014) A review of peripheral biomarkers in major depression: the potential of inflammatory and oxidative stress biomarkers. Prog Neuro-Psychopharmacol Biol Psychiatry 48:102–111CrossRefGoogle Scholar
  48. 48.
    Moya-Perez A, Perez-Villalba A, Benitez-Paez A, Campillo I, Sanz Y (2017) Bifidobacterium Cect 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice. Brain Behav Immun 65:43–56Google Scholar
  49. 49.
    Sharma S, Zhuang Y, Gomez-Pinilla F (2012) High-fat diet transition reduces brain Dha levels associated with altered brain plasticity and behaviour. Sci Rep 2:431CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Hamer M, Batty GD, Kivimaki M (2012) Risk of future depression in people who are obese but metabolically healthy: the English longitudinal study of ageing. Mol Psychiatry 17(9):940–945CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Slyepchenko AMM, Jacka FN, Köhler CA, Barichello T, RS MI, Berk M, Grande I, Foster JA et al (2017) Gut microbiota, bacterial translocation, and interactions with diet: pathophysiological links between major depressive disorder and non-communicable medical comorbidities. Psychother Psychosom 86(1):31–46CrossRefPubMedGoogle Scholar
  52. 52.
    Tanaka M, Yoshida M, Emoto H, Ishii H (2000) Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: basic studies. Eur J Pharmacol 405(1–3):397–406CrossRefPubMedGoogle Scholar
  53. 53.
    Kesby JP, Kim JJ, Scadeng M, Woods G, Kado DM, Olefsky JM, Jeste DV, Achim CL et al (2015) Spatial cognition in adult and aged mice exposed to high-fat diet. PLoS One 10(10):e0140034CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Stepanichev MY, Tishkina AO, Novikova MR, Levshina IP, Freiman SV, Onufriev MV, Levchenko OA, Lazareva NA et al (2016) Anhedonia but not passive floating is an indicator of depressive-like behavior in two chronic stress paradigms. Acta Neurobiol Exp (Wars) 76(4):324–333Google Scholar
  55. 55.
    Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S et al (1995) Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1(11):1155–1161CrossRefPubMedGoogle Scholar
  56. 56.
    Stieg MR, Sievers C, Farr O, Stalla GK, Mantzoros CS (2015) Leptin: a hormone linking activation of neuroendocrine axes with neuropathology. Psychoneuroendocrinology 51:47–57CrossRefPubMedGoogle Scholar
  57. 57.
    Carvalho AF, Rocha DQ, RS MI, Mesquita LM, Köhler CA, Hyphantis TN, Sales PM, Machado-Vieira R et al (2014) Adipokines as emerging depression biomarkers: a systematic review and meta-analysis. J Psychiatr Res 59:28–37CrossRefPubMedGoogle Scholar
  58. 58.
    Liu CS, Carvalho AF, McIntyre RS (2014) Towards a “metabolic” subtype of major depressive disorder: shared pathophysiological mechanisms may contribute to cognitive dysfunction. CNS Neurol Disord Drug Targets 13(10):1693–1707CrossRefPubMedGoogle Scholar
  59. 59.
    Vogelzangs N, Beekman AT, van Reedt Dortland AK, Schoevers RA, Giltay EJ, de Jonge P, Penninx BW (2014) Inflammatory and metabolic dysregulation and the 2-year course of depressive disorders in antidepressant users. Neuropsychopharmacology 39(7):1624–1634CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Sharma A, Bartell SM, Baile CA, Chen B, Podolsky RH, McIndoe RA, She JX (2010) Hepatic gene expression profiling reveals key pathways involved in leptin-mediated weight loss in Ob/Ob mice. PLoS One 5(8):e12147CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Willner P, Towell A, Sampson D, Sophokleous S, Muscat R (1987) Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology 93(3):358–364CrossRefPubMedGoogle Scholar
  62. 62.
    Lu XY, Kim CS, Frazer A, Zhang W (2006) Leptin: a potential novel antidepressant. Proc Natl Acad Sci U S A 103(5):1593–1598CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Buyse M, Ovesjo ML, Goiot H, Guilmeau S, Peranzi G, Moizo L, Walker F, Lewin MJ et al (2001) Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve. Eur J Neurosci 14(1):64–72CrossRefPubMedGoogle Scholar
  64. 64.
    De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL, Boschero AC, Saad MJ, Velloso LA (2005) Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146(10):4192–4199CrossRefPubMedGoogle Scholar
  65. 65.
    Jeon BT, Jeong EA, Shin HJ, Lee Y, Lee DH, Kim HJ, Kang SS, Cho GJ et al (2012) Resveratrol attenuates obesity-associated peripheral and central inflammation and improves memory deficit in mice fed a high-fat diet. Diabetes 61(6):1444–1454CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Puig KL, Floden AM, Adhikari R, Golovko MY, Combs CK (2012) Amyloid precursor protein and proinflammatory changes are regulated in brain and adipose tissue in a murine model of high fat diet-induced obesity. PLoS One 7(1):e30378CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Kempuraj D, Thangavel R, Natteru PA, Selvakumar GP, Saeed D, Zahoor H, Zaheer S, Iyer SS et al (2016) Neuroinflammation induces neurodegeneration. J Neurol Neurosurg Spine 1(1):1003PubMedPubMedCentralGoogle Scholar
  68. 68.
    Hayward JH, Lee SJ (2014) A decade of research on Tlr2 discovering its pivotal role in glial activation and neuroinflammation in neurodegenerative diseases. Exp Neurobiol 23(2):138–147CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Kim C, Ho DH, Suk JE, You S, Michael S, Kang J, Joong Lee S, Masliah E et al (2013) Neuron-released oligomeric alpha-synuclein is an endogenous agonist of Tlr2 for paracrine activation of microglia. Nat Commun 4:1562CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Hwang DH, Kim JA, Lee JY (2016) Mechanisms for the activation of toll-like receptor 2/4 by saturated fatty acids and inhibition by docosahexaenoic acid. Eur J Pharmacol 785:24–35CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Boukouvalas G, Gerozissis K, Kitraki E (2010) Adult consequences of post-weaning high fat feeding on the limbic-Hpa axis of female rats. Cell Mol Neurobiol 30(4):521–530CrossRefPubMedGoogle Scholar
  72. 72.
    Maniam J, Morris MJ (2010) Voluntary exercise and palatable high-fat diet both improve behavioral profile and stress responses in male rats exposed to early life stress: role of hippocampus. Psychoneuroendocrinology 35(10):1553–1564CrossRefPubMedGoogle Scholar
  73. 73.
    Reimann M, Qin N, Gruber M, Bornstein SR, Kirschbaum C, Ziemssen T, Eisenhofer G (2017) Adrenal medullary dysfunction as a feature of obesity. Int J Obes (Lond) 41(5):714–721Google Scholar
  74. 74.
    Gotthardt JD, Verpeut JL, Yeomans BL, Yang JA, Yasrebi A, Roepke TA, Bello NT (2016) Intermittent fasting promotes fat loss with lean mass retention, increased hypothalamic norepinephrine content, and increased neuropeptide Y gene expression in diet-induced obese male mice. Endocrinology 157(2):679–691CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Microbial Ecology, Nutrition and Health Research UnitInstitute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC)Paterna-ValenciaSpain
  2. 2.Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Cell Biology DepartmentUniversity of ValenciaValenciaSpain

Personalised recommendations