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Altered colonic function and microbiota profile in a mouse model of chronic depression

A. J. Park, J. Collins, P. A. Blennerhassett and 4 more

Neurogastroenterology & Motility · 2013 · CC BY-NC

doi:10.1111/nmo.12153

Abstract

Background Depression often coexists with the irritable bowel syndrome ( IBS ) which is characterized by alterations in gut function. There is emerging evidence that the microbial composition (microbiota) of the gut is altered in IBS , but the basis for this is poorly understood. The aim of this study was to determine whether the induction of chronic depression results in changes in the colonic function and in its microbial community, and to explore underlying mechanisms. Methods Bilateral olfactory bulbectomy ( OB x) was used to induce depression‐like behavior in mice. Colonic function was assessed by measuring muscle contractility, pellet excretion, c‐fos activity, and serotonin levels. Microbiota profiles were obtained using denaturing gradient gel electrophoresis ( DGGE ). The hypothalamic‐pituitary axis ( HPA ) was assessed by the hypothalamic expression of corticotropin‐releasing hormone ( CRH ). In separate studies, mice without OB x received CRH via intracerebroventricular ( ICV ) infusion for 4 weeks prior to assessing colonic function and microbiota profiles. Key Results Olfactory bulbectomy mice demonstrated chronic depression‐ and anxiety‐like behaviors associated with elevated central CRH expression and increases in c‐Fos activity, serotonin levels, and motility in the colon. These changes were accompanied by an altered intestinal microbial profile. Central CRH administration produced similar changes in behavior and motility and altered the microbiota profile in the colon. Conclusions & Inferences The induction of chronic depression alters motor activity and the microbial profile in the colon likely via activation of the HPA . These findings provide a basis for linking the behavioral and gastrointestinal manifestations of IBS .

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References 47

  1. 1.

    Folks DG. The interface of psychiatry and irritable bowel syndrome. Curr Psychiatry Rep. 2004;6:210-5.

    Not in our library10.1007/s11920-004-0066-0

  2. 2.

    Malinen E, Rinttila T, Kajander K, et al. Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR. Am J Gastroenterol. 2005;100:373-82.

    Not in our library10.1111/j.1572-0241.2005.40312.x

  3. 3.

    Lyra A, Rinttila T, Nikkila J, et al. Diarrhoea-predominant irritable bow-el syndrome distinguishable by 16S rRNA gene phylotype quantification. World J Gastroenterol. 2009;15:5936-45.

    Not in our library10.3748/wjg.15.5936

  4. 4.
  5. 5.

    Kassinen A, Krogius-Kurikka L, Makivuokko H, et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007;133:24-33.

    Not in our library10.1053/j.gastro.2007.04.005

  6. 6.

    Matto J, Maunuksela L, Kajander K, et al. Composition and temporal stability of gastrointestinal microbiota in irritable bowel syndrome–a longitudinal study in IBS and control subjects. FEMS Immunol Med Microbiol. 2005;43:213-22.

    Not in our library10.1016/j.femsim.2004.08.009

  7. 7.

    Verdu EF, Bercik P, Verma-Gandhu M, et al. Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Gut. 2006;55:182-90.

    Not in our library10.1136/gut.2005.066100

  8. 8.

    Bercik P, Denou E, Collins J, et al. The intestinal microbiota affects central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011;141:599-609.

    Not in our library10.1053/j.gastro.2011.04.052

  9. 9.

    Bailey MT, Coe CL. Maternal separation disrupts the integrity of the intestinal microbiota in infant rhesus monkeys. Dev Psychobiol. 1999;35:146-55.

    Not in our library

  10. 10.

    Bailey MT, Lubach GR, Coe CL. Prenatal stress alters bacterial colonization of the gut in infant monkeys. J Pediatr Gastroenterol Nutr. 2004;38:414-21.

    Not in our library10.1097/00005176-200404000-00009

  11. 11.

    O'Mahony SM, Marchesi JR, Scully P, et al. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry. 2009;65:263-7.

    Not in our library10.1016/j.biopsych.2008.06.026

  12. 12.

    Tannock GW, Savage DC. Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tract. Infect Immun. 1974;9:591-8.

    Not in our library10.1128/iai.9.3.591-598.1974

  13. 13.

    Bailey MT, Dowd SE, Parry NM, Galley JD, Schauer DB, Lyte M. Stressor exposure disrupts commensal microbial populations in the intestines and leads to increased colonization by Citrobacter rodentium. Infect Immun. 2010;78:1509-19.

    Not in our library10.1128/iai.00862-09

  14. 14.

    Bailey MT, Dowd SE, Galley JD, Hufnagle AR, Allen RG, Lyte M. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun. 2011;25:397-407.

    Not in our library10.1016/j.bbi.2010.10.023

  15. 15.

    Cryan JF, Holmes A. The ascent of mouse: advances in modeling human depression and anxiety. Nat Rev Drug Discov. 2005;4:775-90.

    Not in our library10.1038/nrd1825

  16. 16.

    Palazidou E. The neurobiology of depression. Brit Med Bull. 2012;101:127-45.

    Not in our library10.1093/bmb/lds004

  17. 17.

    Harkin A, Kelly JP, Leonard BE. A review of the relevance and validity of olfactory bulbectomy as a model of depression. Clin Neurosci Res. 2003;3:253-62.

    Not in our library

  18. 18.

    Song C, Leonard BE. The olfactory bulbectomised rat as a model of depression. Neurosci Biobehav Rev. 2005;29:627-47.

    Not in our library10.1016/j.neubiorev.2005.03.010

  19. 19.

    Wang D, Noda Y, Tsunekawa H, et al. Behavioural and neurochemical features of olfactory bulbectomized rats resembling depression with comorbid anxiety. Behav Brain Res. 2007;178:262-73.

    Not in our library10.1016/j.bbr.2007.01.003

  20. 20.

    Santos J, Saunders PR, Hanssen NP, et al. Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat. Am J Physiol. 1999;277:G391-9.

    Not in our library10.1152/ajpgi.1999.277.2.g391

  21. 21.

    Cryan JF, Mombereau C, Vassout A. The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev. 2005;29:571-625.

    Not in our library10.1016/j.neubiorev.2005.03.009

  22. 22.

    Haller J, Alicki M. Current animal models of anxiety, anxiety disorders, and anxiolytic drugs. Curr Opin Psychiatry. 2012;25:59-64.

    Not in our library10.1097/yco.0b013e32834de34f

  23. 23.

    Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol. 2003;463:3-33.

    Not in our library10.1016/s0014-2999(03)01272-x

  24. 24.

    Million M, Grigoriadis DE, Sullivan S, et al. A novel water-soluble selective CRF1 receptor antagonist, NBI 35965, blunts stress-induced visceral hyperalgesia and colonic motor function in rats. Brain Res. 2003;985:32-42.

    Not in our library10.1016/s0006-8993(03)03027-0

  25. 25.

    Carrico JA, Pinto FR, Simas C, et al. Assessment of band-based similarity coefficients for automatic type and subtype classification of microbial isolates analyzed by pulsed-field gel electrophoresis. J Clin Microbiol. 2005;43:5483-90.

    Not in our library10.1128/jcm.43.11.5483-5490.2005

  26. 26.

    Fromin N, Hamelin J, Tarnawski S, et al. Statistical analysis of denaturing gel electrophoresis (DGE) fingerprinting patterns. Environ Microbiol. 2002;4:634-43.

    Not in our library10.1046/j.1462-2920.2002.00358.x

  27. 27.

    Costa E, Puhl NJ, Selinger LB, Inglis GD. Characterization of mucosa-associated bacterial communities of the mouse intestine by terminal restriction fragment length polymorphism: utility of sampling strategies and methods to reduce single-stranded DNA artifacts. J Microbiol Methods. 2009;78:175-80.

    Not in our library10.1016/j.mimet.2009.05.011

  28. 28.

    Bruno WJ, Socci ND, Halpern AL. Weighted neighbor joining: a likelihood-based approach to distance-based phylogeny reconstruction. Mol Biol Evol. 2000;17:189-97.

    Not in our library10.1093/oxfordjournals.molbev.a026231

  29. 29.

    Nozu T, Kumei S, Takakusaki K, Ataka K, Fujimiya M, Okumura T. Central orexin-A increases colonic motility in conscious rats. Neurosci Lett. 2011;498:143-6.

    Not in our library10.1016/j.neulet.2011.04.078

  30. 30.

    Vallance BA, Blennerhassett PA, Collins SM. Increased intestinal muscle contractility and worm expulsion in nematode-infected mice. Am J Physiol. 1997;272:G321-7.

    Not in our library10.1152/ajpgi.1997.272.2.g321

  31. 31.

    Dinan TG. Inflammatory markers in depression. Curr Opin Psychiatry. 2009;22:32-6.

    Not in our library10.1097/yco.0b013e328315a561

  32. 32.

    Raison CL, Miller AH. Is depression an inflammatory disorder? Curr Psychiatry Rep. 2011;13:467-75.

    Not in our library10.1007/s11920-011-0232-0

  33. 33.

    Raedler TJ. Inflammatory mechanisms in major depressive disorder. Curr Opin Psychiatry. 2011;24:519-25.

    Not in our library10.1097/yco.0b013e32834b9db6

  34. 34.

    Connor TJ, Harkin A, Kelly JP, Leonard BE. Olfactory bulbectomy provokes a suppression of interleukin-1beta and tumour necrosis factor-alpha production in response to an in vivo challenge with lipopolysaccharide: effect of chronic desipramine treatment. NeuroImmunoModulation. 2000;7:27-35.

    Not in our library10.1159/000026417

  35. 35.

    Meguid MM, Gleason JR, Yang ZJ. Olfactory bulbectomy in rats modulates feeding pattern but not total food intake. Physiol Behav. 1993;54:471-5.

    Not in our library10.1016/0031-9384(93)90238-b

  36. 36.

    Meguid MM, Koseki M, Yang ZJ, Gleason JR, Laviano A. Acute adaptive changes in food intake pattern following olfactory ablation in rats. NeuroReport. 1997;8:1439-44.

    Not in our library10.1097/00001756-199704140-00023

  37. 37.

    Lechin F, van der Dijs B, Acosta E, Gómez F, Lechin E, Arocha L. Distal colon motility and clinical parameters in depression. J Affect Disord. 1983;5:19-26.

    Not in our library10.1016/0165-0327(83)90032-0

  38. 38.

    Rodes L, Paul A, Coussa-Charley M, et al. Transit time affects the community stability of Lactobacillus and Bifidobacterium species in an in vitro model of human colonic microbiotia. Artif Cells Blood Substit Immobil Biotechnol. 2011;39:351-6.

    Not in our library10.3109/10731199.2011.622280

  39. 39.

    O'Malley D, Julio-Pieper M, Gibney SM, Dinan TG, Cryan JF. Distinct alterations in colonic morphology and physiology in two rat models of enhanced stress-induced anxiety and depression-like behaviour. Stress. 2010;13:114-22.

    Not in our library10.3109/10253890903067418

  40. 40.

    O'Mahony SM, Hyland NP, Dinan TG, Cryan JF. Maternal separation as a model of brain-gut axis dysfunction. Psychopharmacology. 2011;214:71-88.

    Not in our library10.1007/s00213-010-2010-9

All 47 references

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