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Psychopharmacology

, Volume 236, Issue 5, pp 1671–1685 | Cite as

Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function

  • Sofia Cussotto
  • Conall R. Strain
  • Fiona Fouhy
  • Ronan G. Strain
  • Veronica L. Peterson
  • Gerard Clarke
  • Catherine Stanton
  • Timothy G. DinanEmail author
  • John F. CryanEmail author
Original Investigation

Abstract

Rationale

Growing evidence supports a role for the microbiota in regulating gut-brain interactions and, thus, psychiatric disorders. Despite substantial scientific efforts to delineate the mechanism of action of psychotropic medications at a central nervous system (CNS) level, there remains a critical lack of understanding on how these drugs might affect the microbiota and gut physiology.

Objectives

We investigated the antimicrobial activity of psychotropics against two bacterial strain residents in the human gut, Lactobacillus rhamnosus and Escherichia coli. In addition, we examined the impact of chronic treatment with these drugs on microbiota and intestinal parameters in the rat.

Results

In vitro fluoxetine and escitalopram showed differential antimicrobial effects. Lithium, valproate and aripiprazole administration significantly increased microbial species richness and diversity, while the other treatments were not significantly different from controls. At the genus level, several species belonging to Clostridium, Peptoclostridium, Intestinibacter and Christenellaceae were increased following treatment with lithium, valproate and aripiprazole when compared to the control group. Animals treated with escitalopram, venlafaxine, fluoxetine and aripiprazole exhibited an increased permeability in the ileum.

Conclusions

These data show that psychotropic medications differentially influence the composition of gut microbiota in vivo and that fluoxetine and escitalopram have specific antimicrobial activity in vitro. Interestingly, drugs that significantly altered gut microbial composition did not increase intestinal permeability, suggesting that the two factors are not causally linked. Overall, unravelling the impact of psychotropics on gastrointestinal and microbiota measures offers the potential to provide critical insight into the mechanism of action and side effects of these medications.

Keywords

Psychotropics Intestinal permeability Gut microbiota Diversity Richness Short-chain fatty acids Antimicrobial 

Notes

Acknowledgments

The authors gratefully acknowledge Pat Fitzgerald, Gonzalo Rabasa, Karen Scott, Gilliard Lach, Gerry Moloney, Anna Golubeva and Kieran Rea for their invaluable support. We would also like to acknowledge Wiley Barton for his assistance in R scripts and the Teagasc Sequencing Facility, Dr. Paul Cotter, Dr. Fiona Crispie and Ms. Laura Finnegan.

Funding

APC Microbiome Ireland is a research centre funded by Science Foundation Ireland (SFI), through the Irish Government’s National Development Plan (grant no. 12/RC/2273). JFC, TGD and CS have research funding from Dupont Nutrition Biosciences APS, Cremo SA, Alkermes Inc., 4D Pharma PLC, Mead Johnson Nutrition, Nutricia Danone, Suntory Wellness. JFC, TGD, CS and GC have spoken at meetings sponsored by food and pharmaceutical companies.

Compliance with ethical standards

Experiments were conducted in accordance with the European Directive 2010/63/EU. Approval by the Animal Experimentation Ethics Committee of University College Cork was obtained before commencement of all animal-related experiments.

Conflict of interest

All other authors declare that they have no conflict of interest.

Supplementary material

213_2018_5006_MOESM1_ESM.docx (567 kb)
ESM 1 (DOCX 566 kb)
213_2018_5006_MOESM2_ESM.xlsx (15 kb)
ESM 2 (XLSX 15 kb)

References

  1. Ackenheil M, Weber K (2004) Differing response to antipsychotic therapy in schizophrenia: pharmacogenomic aspects. Dialogues Clin Neurosci 6:71–77PubMedPubMedCentralGoogle Scholar
  2. Al-Harbi KS (2012) Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Preference Adherence 6:369–388CrossRefPubMedGoogle Scholar
  3. Ariel L, Inbar S, Edut S, Richter-Levin G (2017) Fluoxetine treatment is effective in a rat model of childhood-induced post-traumatic stress disorder. Transl Psychiatry 7:1260CrossRefPubMedPubMedCentralGoogle Scholar
  4. Ayaz M, Subhan F, Ahmed J, Khan A-u, Ullah F, Ullah I, Ali G, Syed N-i-H, Hussain S (2015a) Sertraline enhances the activity of antimicrobial agents against pathogens of clinical relevance. J Biol Res 22:4Google Scholar
  5. Ayaz M, Subhan F, Ahmed J, Khan AU, Ullah F, Ullah I, Ali G, Syed NI, Hussain S (2015b) Sertraline enhances the activity of antimicrobial agents against pathogens of clinical relevance. J Biol Res (Thessalon) 22:4CrossRefGoogle Scholar
  6. Bahr SM, Tyler BC, Wooldridge N, Butcher BD, Burns TL, Teesch LM, Oltman CL, Azcarate-Peril MA, Kirby JR, Calarge CA (2015a) Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children. Transl Psychiatry 5:e652CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bahr SM, Weidemann BJ, Castro AN, Walsh JW, deLeon O, Burnett CML, Pearson NA, Murry DJ, Grobe JL, Kirby JR (2015b) Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure. EBioMedicine 2:1725–1734CrossRefPubMedCentralGoogle Scholar
  8. Bercik P, Collins SM, Verdu EF (2012) Microbes and the gut-brain axis. Neurogastroenterology Motility 24:405–413CrossRefPubMedGoogle Scholar
  9. Beyazyüz M, Albayrak Y, Eğilmez OB, Albayrak N, Beyazyüz E (2013) Relationship between SSRIs and metabolic syndrome abnormalities in patients with generalized anxiety disorder: a prospective study. Psychiatry Investigation 10:148–154CrossRefPubMedPubMedCentralGoogle Scholar
  10. Bischoff SC, Mailer R, Pabst O, Weier G, Sedlik W, Li Z, Chen JJ, Murphy DL, Gershon MD (2009) Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice. Am J Physiol Gastrointest Liver Physiol 296:G685–G695CrossRefPubMedGoogle Scholar
  11. Bohnert JA, Szymaniak-Vits M, Schuster S, Kern WV (2011a) Efflux inhibition by selective serotonin reuptake inhibitors in Escherichia coli. J Antimicrob Chemother 66:2057–2060CrossRefPubMedGoogle Scholar
  12. Bohnert JA, Szymaniak-Vits M, Schuster S, Kern WV (2011b) Efflux inhibition by selective serotonin reuptake inhibitors in Escherichia coli. J Antimicrob Chemother 66:2057–2060CrossRefPubMedGoogle Scholar
  13. Cani PD, Lecourt E, Dewulf EM, Sohet FM, Pachikian BD, Naslain D, De Backer F, Neyrinck AM, Delzenne NM (2009) Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am J Clin Nutr 90:1236–1243CrossRefPubMedGoogle Scholar
  14. Caparrós-Martín JA, Lareu RR, Ramsay JP, Peplies J, Reen FJ, Headlam HA, Ward NC, Croft KD, Newsholme P, Hughes JD, O’Gara F (2017) Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism. Microbiome 5:95CrossRefPubMedPubMedCentralGoogle Scholar
  15. Chen JX, Pan H, Rothman TP, Wade PR, Gershon MD (1998) Guinea pig 5-HT transporter: cloning, expression, distribution, and function in intestinal sensory reception. Am J Phys 275:G433–G448Google Scholar
  16. Chen JJ, Li Z, Pan H, Murphy DL, Tamir H, Koepsell H, Gershon MD (2001) Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: abnormal intestinal motility and the expression of cation transporters. J Neurosci 21:6348–6361CrossRefPubMedGoogle Scholar
  17. Chen L, Wilson JE, Koenigsknecht MJ, Chou WC, Montgomery SA, Truax AD, Brickey WJ, Packey CD, Maharshak N, Matsushima GK, Plevy SE, Young VB, Sartor RB, Ting JP (2017) NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth. Nat Immunol 18:541–551CrossRefPubMedPubMedCentralGoogle Scholar
  18. Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, Crowell MD, Sharkey KA, Gershon MD, Mawe GM, Moses PL (2004) Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology 126:1657–1664CrossRefPubMedGoogle Scholar
  19. Coban AY, Tanriverdi Cayci Y, Keles Uludag S, Durupinar B (2009) Investigation of antibacterial activity of sertralin. Mikrobiyol Bul 43:651–656PubMedGoogle Scholar
  20. Collins SM, Surette M, Bercik P (2012) The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 10:735–742CrossRefPubMedGoogle Scholar
  21. Correll CU, Detraux J, De Lepeleire J, De Hert M (2015) Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry 14:119–136CrossRefPubMedPubMedCentralGoogle Scholar
  22. Cryan JF, Dinan TG (2012a) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13:701–712CrossRefPubMedGoogle Scholar
  23. Cryan JF, Dinan TG (2012b) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13:701–712CrossRefPubMedGoogle Scholar
  24. Davey KJ, O’Mahony SM, Schellekens H, O’Sullivan O, Bienenstock J, Cotter PD, Dinan TG, Cryan JF (2012) Gender-dependent consequences of chronic olanzapine in the rat: effects on body weight, inflammatory, metabolic and microbiota parameters. Psychopharmacology 221:155–169CrossRefPubMedGoogle Scholar
  25. Davey KJ, Cotter PD, O'Sullivan O, Crispie F, Dinan TG, Cryan JF, O'Mahony SM (2013) Antipsychotics and the gut microbiome: olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Transl Psychiatry 3:e309CrossRefPubMedPubMedCentralGoogle Scholar
  26. De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, Backhed F, Mithieux G (2014) Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156:84–96CrossRefPubMedGoogle Scholar
  27. van de Wouw M, Schellekens H, Dinan TG, Cryan JF (2017) Microbiota-gut-brain axis: modulator of host metabolism and appetite. J Nutr 147:727–745CrossRefPubMedGoogle Scholar
  28. Dinan TG, Stanton C, Cryan JF (2013) Psychobiotics: a novel class of psychotropic. Biol Psychiatry 74:720–726CrossRefPubMedGoogle Scholar
  29. Dinan TG, Borre YE, Cryan JF (2014) Genomics of schizophrenia: time to consider the gut microbiome? Mol Psychiatry 19:1252–1257CrossRefPubMedGoogle Scholar
  30. Erny D, Hrabe de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, Keren-Shaul H, Mahlakoiv T, Jakobshagen K, Buch T, Schwierzeck V, Utermohlen O, Chun E, Garrett WS, McCoy KD, Diefenbach A, Staeheli P, Stecher B, Amit I, Prinz M (2015) Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 18:965–977CrossRefPubMedPubMedCentralGoogle Scholar
  31. Evans SJ, Bassis CM, Hein R, Assari S, Flowers SA, Kelly MB, Young VB, Ellingrod VE, McInnis MG (2017) The gut microbiome composition associates with bipolar disorder and illness severity. J Psychiatr Res 87:23–29CrossRefPubMedGoogle Scholar
  32. Falony G, Joossens M, Vieira-Silva S, Wang J, Darzi Y, Faust K, Kurilshikov A, Bonder MJ, Valles-Colomer M, Vandeputte D, Tito RY, Chaffron S, Rymenans L, Verspecht C, De Sutter L, Lima-Mendez G, D'Hoe K, Jonckheere K, Homola D, Garcia R, Tigchelaar EF, Eeckhaudt L, Fu J, Henckaerts L, Zhernakova A, Wijmenga C, Raes J (2016) Population-level analysis of gut microbiome variation. Science 352:560–564CrossRefPubMedGoogle Scholar
  33. Flowers SA, Evans SJ, Ward KM, McInnis MG, Ellingrod VL (2017a) Interaction between atypical antipsychotics and the gut microbiome in a bipolar disease cohort. Pharmacotherapy 37:261–267CrossRefPubMedGoogle Scholar
  34. Flowers SA, Evans SJ, Ward KM, McInnis MG, Ellingrod VL (2017b) Interaction between atypical antipsychotics and the gut microbiome in a bipolar disease cohort. Pharmacotherapy: J Human Pharmacology Drug Therapy 37:261–267CrossRefGoogle Scholar
  35. Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, Prifti E, Vieira-Silva S, Gudmundsdottir V, Krogh Pedersen H, Arumugam M, Kristiansen K, Yvonne Voigt A, Vestergaard H, Hercog R, Igor Costea P, Roat Kultima J, Li J, Jørgensen T, Levenez F, Dore J, Meta HIT c, Bjørn Nielsen H, Brunak S, Raes J, Hansen T, Wang J, Dusko Ehrlich S, Bork P, Pedersen O (2015) Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528:262–266CrossRefPubMedPubMedCentralGoogle Scholar
  36. Foster JA, McVey Neufeld K-A (2013) Gut–brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 36:305–312CrossRefGoogle Scholar
  37. Freier TA, Beitz DC, Li L, Hartman PA (1994) Characterization of Eubacterium coprostanoligenes sp. nov., a cholesterol-reducing anaerobe. Int J Syst Bacteriol 44:137–142CrossRefPubMedGoogle Scholar
  38. Gafoor R, Booth HP, Gulliford MC (2018) Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study. BMJ 361:k1951CrossRefPubMedPubMedCentralGoogle Scholar
  39. Golubeva AV, Joyce SA, Moloney G, Burokas A, Sherwin E, Arboleya S, Flynn I, Khochanskiy D, Moya-Pérez A, Peterson V, Rea K, Murphy K, Makarova O, Buravkov S, Hyland NP, Stanton C, Clarke G, Gahan CGM, Dinan TG, Cryan JF (2017) Microbiota-related changes in bile acid and tryptophan metabolism are associated with gastrointestinal dysfunction in a mouse model of autism. EBioMedicine 24:166–178CrossRefPubMedPubMedCentralGoogle Scholar
  40. Goodrich JK, Davenport ER, Waters JL, Clark AG, Ley RE (2016) Cross-species comparisons of host genetic associations with the microbiome. Science 352:532–535CrossRefPubMedPubMedCentralGoogle Scholar
  41. Grubbs FE (1950) Sample criteria for testing outlying observations. Ann Math Stat 21:27–58CrossRefGoogle Scholar
  42. Hatta K, Ito H (2014) Strategies for early non-response to antipsychotic drugs in the treatment of acute-phase schizophrenia. Clinical Psychopharmacology Neuroscience 12:1–7CrossRefPubMedGoogle Scholar
  43. Haub S, Ritze Y, Bergheim I, Pabst O, Gershon MD, Bischoff SC (2010) Enhancement of intestinal inflammation in mice lacking interleukin 10 by deletion of the serotonin reuptake transporter. Neurogastroenterol Motil 22(826–834):e229Google Scholar
  44. Huuskonen J, Suuronen T, Nuutinen T, Kyrylenko S, Salminen A (2004) Regulation of microglial inflammatory response by sodium butyrate and short-chain fatty acids. Br J Pharmacol 141:874–880CrossRefPubMedPubMedCentralGoogle Scholar
  45. Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, Wang W, Tang W, Tan Z, Shi J, Li L, Ruan B (2015) Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun 48:186–194CrossRefPubMedGoogle Scholar
  46. Kaminska K, Rogoz Z (2016) The antidepressant- and anxiolytic-like effects following co-treatment with escitalopram and risperidone in rats. J Physiol Pharmacol 67:471–480PubMedGoogle Scholar
  47. Kao AC-C, Spitzer S, Anthony DC, Lennox B, Burnet PWJ (2018) Prebiotic attenuation of olanzapine-induced weight gain in rats: analysis of central and peripheral biomarkers and gut microbiota. Transl Psychiatry 8:66CrossRefPubMedPubMedCentralGoogle Scholar
  48. Karl JP, Margolis LM, Madslien EH, Murphy NE, Castellani JW, Gundersen Y, Hoke AV, Levangie MW, Kumar R, Chakraborty N, Gautam A, Hammamieh R, Martini S, Montain SJ, Pasiakos SM (2017) Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress. Am J Physiol Gastrointest Liver Physiol 312:G559–g571CrossRefPubMedGoogle Scholar
  49. Kelly JR, Borre Y, O’ Brien C, Patterson E, El Aidy S, Deane J, Kennedy PJ, Beers S, Scott K, Moloney G, Hoban AE, Scott L, Fitzgerald P, Ross P, Stanton C, Clarke G, Cryan JF, Dinan TG (2016) Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res 82:109–118CrossRefGoogle Scholar
  50. Kim KA, Gu W, Lee IA, Joh EH, Kim DH (2012) High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One 7:e47713CrossRefPubMedPubMedCentralGoogle Scholar
  51. Kiraly DD, Walker DM, Calipari ES, Labonte B, Issler O, Pena CJ, Ribeiro EA, Russo SJ, Nestler EJ (2016) Alterations of the host microbiome affect behavioral responses to cocaine. Sci Rep 6:35455CrossRefPubMedPubMedCentralGoogle Scholar
  52. Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F (2016) From dietary Fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165:1332–1345CrossRefPubMedGoogle Scholar
  53. Kong F, Hua Y, Zeng B, Ning R, Li Y, Zhao J (2016) Gut microbiota signatures of longevity. Curr Biol 26:R832–R833CrossRefPubMedGoogle Scholar
  54. Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vadder F, Arora T, Hallen A, Martens E, Björck I, Bäckhed F (2015) Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab 22:971–982CrossRefPubMedGoogle Scholar
  55. Li L, Buhman KK, Hartman PA, Beitz DC (1995) Hypocholesterolemic effect of Eubacterium coprostanoligenes ATCC 51222 in rabbits. Lett Appl Microbiol 20:137–140CrossRefPubMedGoogle Scholar
  56. Li L, Batt SM, Wannemuehler M, Dispirito A, Beitz DC (1998) Effect of feeding of a cholesterol-reducing bacterium, Eubacterium coprostanoligenes, to germ-free mice. Lab Anim Sci 48:253–255PubMedGoogle Scholar
  57. Li M, Wang B, Sun X, Tang Y, Wei X, Ge B, Tang Y, Deng Y, He C, Yuan J, Li X (2017) Upregulation of intestinal barrier function in mice with DSS-induced colitis by a defined bacterial consortium is associated with expansion of IL-17A producing gamma delta T cells. Front Immunol 8:824CrossRefPubMedPubMedCentralGoogle Scholar
  58. Ling Z, Li Z, Liu X, Cheng Y, Luo Y, Tong X, Yuan L, Wang Y, Sun J, Li L, Xiang C (2014) Altered fecal microbiota composition associated with food allergy in infants. Appl Environ Microbiol 80:2546–2554CrossRefPubMedPubMedCentralGoogle Scholar
  59. López-Contreras BE, Morán-Ramos S, Villarruel-Vázquez R, Macías-Kauffer L, Villamil-Ramírez H, León-Mimila P, Vega-Badillo J, Sánchez-Muñoz F, Llanos-Moreno LE, Canizalez-Román A, Río-Navarro B, Ibarra-González I, Vela-Amieva M, Villarreal-Molina T, Ochoa-Leyva A, Aguilar-Salinas CA, Canizales-Quinteros S (2018) Composition of gut microbiota in obese and normal-weight Mexican school-age children and its association with metabolic traits. Pediatric Obesity 13:381–388CrossRefPubMedGoogle Scholar
  60. Luna RA, Foster JA (2015) Gut brain axis: diet microbiota interactions and implications for modulation of anxiety and depression. Curr Opin Biotechnol 32:35–41CrossRefPubMedGoogle Scholar
  61. Lyons L, ElBeltagy M, Bennett G, Wigmore P (2012) Fluoxetine counteracts the cognitive and cellular effects of 5-fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery. PLoS One 7:e30010CrossRefPubMedPubMedCentralGoogle Scholar
  62. Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, Brochado AR, Fernandez KC, Dose H, Mori H, Patil KR, Bork P, Typas A (2018) Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555:623–628CrossRefPubMedPubMedCentralGoogle Scholar
  63. Mayer EA, Knight R, Mazmanian SK, Cryan JF, Tillisch K (2014) Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci 34:15490–15496CrossRefPubMedPubMedCentralGoogle Scholar
  64. Mayer EA, Tillisch K, Gupta A (2015) Gut/brain axis and the microbiota. J Clin Invest 125:926–938CrossRefPubMedPubMedCentralGoogle Scholar
  65. Monti B, Gatta V, Piretti F, Raffaelli SS, Virgili M, Contestabile A (2010) Valproic acid is neuroprotective in the rotenone rat model of Parkinson’s disease: involvement of alpha-synuclein. Neurotox Res 17:130–141CrossRefPubMedGoogle Scholar
  66. Morgan AP, Crowley JJ, Nonneman RJ, Quackenbush CR, Miller CN, Ryan AK, Bogue MA, Paredes SH, Yourstone S, Carroll IM, Kawula TH, Bower MA, Sartor RB, Sullivan PF (2014) The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse. PLoS One 9:e115225CrossRefPubMedPubMedCentralGoogle Scholar
  67. Morrison DJ, Preston T (2016) Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 7:189–200CrossRefPubMedPubMedCentralGoogle Scholar
  68. Munoz-Bellido JL, Munoz-Criado S, Garcia-Rodriguez JA (1996) In-vitro activity of psychiatric drugs against Corynebacterium urealyticum (Corynebacterium group D2). J Antimicrob Chemother 37:1005–1009CrossRefPubMedGoogle Scholar
  69. Munoz-Bellido JL, Munoz-Criado S, Garcia-Rodriguez JA (2000) Antimicrobial activity of psychotropic drugs: selective serotonin reuptake inhibitors. Int J Antimicrob Agents 14:177–180CrossRefPubMedGoogle Scholar
  70. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM (2013) The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 54:2325–2340CrossRefGoogle Scholar
  71. Naseribafrouei A, Hestad K, Avershina E, Sekelja M, Linløkken A, Wilson R, Rudi K (2014) Correlation between the human fecal microbiota and depression. Neurogastroenterology Motility 26:1155–1162CrossRefPubMedGoogle Scholar
  72. Nelson JC (1998) Treatment of antidepressant nonresponders: augmentation or switch? J Clin Psychiatry 59(Suppl 15):35–41PubMedGoogle Scholar
  73. O’Leary OF, O’Connor RM, Cryan JF (2012) Lithium-induced effects on adult hippocampal neurogenesis are topographically segregated along the dorso-ventral axis of stressed mice. Neuropharmacology 62:247–255CrossRefPubMedGoogle Scholar
  74. O’Mahony SM, Felice VD, Nally K, Savignac HM, Claesson MJ, Scully P, Woznicki J, Hyland NP, Shanahan F, Quigley EM, Marchesi JR, O’Toole PW, Dinan TG, Cryan JF (2014) Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats. Neuroscience 277:885–901CrossRefPubMedGoogle Scholar
  75. Olguner Eker Ö, ÖZsoy S, Eker B, DoĞAn H (2017) Metabolic effects of antidepressant treatment. Archives Neuropsychiatry 54:49–56CrossRefGoogle Scholar
  76. Olivares, M., Neef, A., Castillejo, G., Palma, G. D., Varea, V., Capilla, A., Palau, F., Nova, E., Marcos, A., Polanco, I., Ribes-Koninckx, C., Ortigosa, L., Izquierdo, L., Sanz, Y., 2014. The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease. GutGoogle Scholar
  77. Ott B, Skurk T, Hastreiter L, Lagkouvardos I, Fischer S, Büttner J, Kellerer T, Clavel T, Rychlik M, Haller D, Hauner H (2017) Effect of caloric restriction on gut permeability, inflammation markers, and fecal microbiota in obese women. Sci Rep 7:11955CrossRefPubMedPubMedCentralGoogle Scholar
  78. Paquin-Proulx D, Ching C, Vujkovic-Cvijin I, Fadrosh D, Loh L, Huang Y, Somsouk M, Lynch SV, Hunt PW, Nixon DF, SenGupta D (2016) Bacteroides are associated with GALT iNKT cell function and reduction of microbial translocation in HIV-1 infection. Mucosal Immunol 10:69CrossRefPubMedPubMedCentralGoogle Scholar
  79. Raman M, Ahmed I, Gillevet PM, Probert CS, Ratcliffe NM, Smith S, Greenwood R, Sikaroodi M, Lam V, Crotty P, Bailey J, Myers RP, Rioux KP (2013) Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clinical Gastroenterology Hepatology 11 e863:868–875CrossRefGoogle Scholar
  80. Rath HC, Herfarth HH, Ikeda JS, Grenther WB, Hamm TE Jr, Balish E, Taurog JD, Hammer RE, Wilson KH, Sartor RB (1996) Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rats. J Clin Invest 98:945–953CrossRefPubMedPubMedCentralGoogle Scholar
  81. Ren D, Li L, Schwabacher AW, Young JW, Beitz DC (1996) Mechanism of cholesterol reduction to coprostanol by Eubacterium coprostanoligenes ATCC 51222. Steroids 61:33–40CrossRefPubMedGoogle Scholar
  82. Reynolds GP, Kirk SL (2010) Metabolic side effects of antipsychotic drug treatment – pharmacological mechanisms. Pharmacol Ther 125:169–179CrossRefPubMedGoogle Scholar
  83. Schroeder FA, Lin CL, Crusio WE, Akbarian S (2007) Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol Psychiatry 62:55–64CrossRefPubMedGoogle Scholar
  84. Schubert AM, Rogers MA, Ring C, Mogle J, Petrosino JP, Young VB, Aronoff DM, Schloss PD (2014) Microbiome data distinguish patients with Clostridium difficile infection and non-C. difficile-associated diarrhea from healthy controls. MBio 5:e01021–e01014CrossRefPubMedPubMedCentralGoogle Scholar
  85. Schwarz E, Maukonen J, Hyytiäinen T, Kieseppä T, Orešič M, Sabunciyan S, Mantere O, Saarela M, Yolken R, Suvisaari J (2017) Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response. Schizophr Res 192:398–403CrossRefPubMedGoogle Scholar
  86. Scott KA, Ida M, Peterson VL, Prenderville JA, Moloney GM, Izumo T, Murphy K, Murphy A, Ross RP, Stanton C, Dinan TG, Cryan JF (2017) Revisiting Metchnikoff: age-related alterations in microbiota-gut-brain axis in the mouse. Brain Behav Immun 65:20–32CrossRefPubMedGoogle Scholar
  87. Segnitz N, Schmitt A, Gebicke-Harter PJ, Zink M (2009) Differential expression of glutamate transporter genes after chronic oral treatment with aripiprazole in rats. Neurochem Int 55:619–628CrossRefPubMedGoogle Scholar
  88. Sogaard B, Mengel H, Rao N, Larsen F (2005) The pharmacokinetics of escitalopram after oral and intravenous administration of single and multiple doses to healthy subjects. J Clin Pharmacol 45:1400–1406CrossRefPubMedGoogle Scholar
  89. Thursby E, Juge N (2017) Introduction to the human gut microbiota. Biochem J 474:1823–1836CrossRefPubMedPubMedCentralGoogle Scholar
  90. Torres-Fuentes C, Schellekens H, Dinan TG, Cryan JF (2017) The microbiota–gut–brain axis in obesity. Lancet Gastroenterology Hepatology 2:747–756CrossRefPubMedGoogle Scholar
  91. Tschoner A, Engl J, Laimer M, Kaser S, Rettenbacher M, Fleischhacker WW, Patsch JR, Ebenbichler CF (2007) Metabolic side effects of antipsychotic medication. Int J Clin Pract 61:1356–1370CrossRefPubMedGoogle Scholar
  92. Ulluwishewa D, Anderson RC, McNabb WC, Moughan PJ, Wells JM, Roy NC (2011) Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr 141:769–776CrossRefGoogle Scholar
  93. Vidal R, Valdizan E, Vilaró M, Pazos A, Castro E (2010) Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in rats. Br J Pharmacol 161:695–706CrossRefPubMedPubMedCentralGoogle Scholar
  94. Wade PR, Chen J, Jaffe B, Kassem IS, Blakely RD, Gershon MD (1996) Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci 16:2352–2364CrossRefPubMedPubMedCentralGoogle Scholar
  95. Walter J (2008) Ecological role of lactobacilli in the gastrointestinal tract: implications for fundamental and biomedical research. Appl Environ Microbiol 74:4985–4996CrossRefPubMedPubMedCentralGoogle Scholar
  96. Watase K, Gatchel JR, Sun Y, Emamian E, Atkinson R, Richman R, Mizusawa H, Orr HT, Shaw C, Zoghbi HY (2007) Lithium therapy improves neurological function and hippocampal dendritic arborization in a spinocerebellar ataxia type 1 mouse model. PLoS Med 4:e182CrossRefPubMedPubMedCentralGoogle Scholar
  97. World Health Organization, 2017. Depression and other common mental disorders: global health estimates. GenevaGoogle Scholar
  98. Wu H, Esteve E, Tremaroli V, Khan MT, Caesar R, Mannerås-Holm L, Ståhlman M, Olsson LM, Serino M, Planas-Fèlix M, Xifra G, Mercader JM, Torrents D, Burcelin R, Ricart W, Perkins R, Fernàndez-Real JM, Bäckhed F (2017) Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med 23:850–858CrossRefPubMedGoogle Scholar
  99. Xie, Y., Zhou, G., Wang, C., Xu, X., Li, C., 2018. Temporal changes in gut microbiota and signaling molecules of the gut-brain axis in mice fed meat protein diets. bioRxivGoogle Scholar
  100. Yamada T, Inui A, Hayashi N, Fujimura M, Fujimiya M (2003) Serotonin stimulates endotoxin translocation via 5-HT3 receptors in the rat ileum. Am J Physiol Gastrointest Liver Physiol 284:G782–G788CrossRefPubMedGoogle Scholar
  101. Zhan G, Yang N, Li S, Huang N, Fang X, Zhang J, Zhu B, Yang L, Yang C, Luo A (2018) Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice. Aging (Albany NY) 10:1257–1267CrossRefGoogle Scholar
  102. Zheng P, Zeng B, Zhou C, Liu M, Fang Z, Xu X, Zeng L, Chen J, Fan S, Du X, Zhang X, Yang D, Yang Y, Meng H, Li W, Melgiri ND, Licinio J, Wei H, Xie P (2016) Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Mol Psychiatry 21:786–796CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Sofia Cussotto
    • 1
    • 2
  • Conall R. Strain
    • 1
    • 3
  • Fiona Fouhy
    • 1
    • 3
  • Ronan G. Strain
    • 1
    • 3
  • Veronica L. Peterson
    • 1
    • 2
  • Gerard Clarke
    • 1
    • 4
  • Catherine Stanton
    • 1
    • 3
    • 4
  • Timothy G. Dinan
    • 1
    • 4
    Email author
  • John F. Cryan
    • 1
    • 2
    Email author
  1. 1.APC Microbiome IrelandUniversity College CorkCorkIreland
  2. 2.Department of Anatomy and NeuroscienceUniversity College CorkCorkIreland
  3. 3.Teagasc Food Research Centre, MooreparkFermoyIreland
  4. 4.Department of Psychiatry and Neurobehavioural ScienceUniversity College CorkCorkIreland

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