Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior

eLife

Volumn 5, Issue APRIL2016, 2016, Pages

  Gacias, Mar ^a   Gaspari, Sevasti ^a   Santos, Patricia Mae G ^a   Tamburini, Sabrina ^a   Andrade, Monica ^a   Zhang, Fan ^a   Shen, Nan ^a   Tolstikov, Vladimir ^b   Kiebish, Michael A ^b   Dupree, Jeffrey L ^c   Zachariou, Venetia ^a   Clemente, Jose C ^a   Casaccia, Patrizia ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b Berg LLC   (United States)

^c VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPHOTERICIN B; METRONIDAZOLE; NEOMYCIN; RNA 16S; VANCOMYCIN; CRESOL;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BEHAVIOR DISORDER; CLOSTRIDIALES; CONTROLLED STUDY; DIABETES MELLITUS; DNA EXTRACTION; EXPERIMENTAL BEHAVIORAL TEST; FORCED SWIM TEST; GENE EXPRESSION; GENE SEQUENCE; GENETIC DIFFERENCE; GENETIC TRANSCRIPTION; GENOTYPE ENVIRONMENT INTERACTION; IMMUNOCYTOCHEMISTRY; IMMUNOHISTOCHEMISTRY; INTESTINE FLORA; LACHNOSPIRACEAE; LOCOMOTION; MALE; METABOLOME; MOUSE; NONHUMAN; OLIGODENDROGLIA; POLYMERASE CHAIN REACTION; PREFRONTAL CORTEX; RNA ISOLATION; RUMINOCOCCACEAE; SOCIAL BEHAVIOR; ANIMAL; BACTERIUM; C57BL MOUSE; GENE EXPRESSION REGULATION; METABOLISM; METABOLOMICS; NONOBESE DIABETIC MOUSE; PHYSIOLOGY;

ANIMALS; BACTERIA; CRESOLS; GASTROINTESTINAL MICROBIOME; GENE EXPRESSION REGULATION; METABOLOMICS; MICE, INBRED C57BL; MICE, INBRED NOD; PREFRONTAL CORTEX; SOCIAL BEHAVIOR; TRANSCRIPTION, GENETIC;

EID: 84971575056     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.13442     Document Type: Article

References (78)

1. Addolorato G, Capristo E, Stefanini GF, Gasbarrini G. 1997. Inflammatory bowel disease: A study of the association between anxiety and depression, physical morbidity, and nutritional status. Scandinavian Journal of Gastroenterology 32:1013–1021. doi: 10.3109/00365529709011218
2. Aston C, Jiang L, Sokolov BP. 2005. Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. Molecular Psychiatry 10: 309–322. doi: 10.1038/sj.mp.4001565
3. Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y, Narushima S, Suda W, Imaoka A, Setoyama H, Nagamori T, Ishikawa E, Shima T, Hara T, Kado S, Jinnohara T, Ohno H, Kondo T, Toyooka K, Watanabe E, Yokoyama S, et al. 2015. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163:367–380. doi: 10.1016/j.cell.2015.08.058
4. Audet MC, McQuaid RJ, Merali Z, Anisman H. 2014. Cytokine variations and mood disorders: Influence of social stressors and social support. Frontiers in Neuroscience 8:416. doi: 10.3389/fnins.2014.00416
5. Bercik P, Denou E, Collins J, Jackson W, Lu J, Jury J, Deng Y, Blennerhassett P, Macri J, McCoy KD, Verdu EF, Collins SM. 2011. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141:599–609. doi: 10.1053/j.gastro.2011.04.052
6. Bercik P, Verdu EF, Foster JA, Macri J, Potter M, Huang X, Malinowski P, Jackson W, Blennerhassett P, Neufeld KA, Lu J, Khan WI, Corthesy-Theulaz I, Cherbut C, Bergonzelli GE, Collins SM. 2010. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology 139:e2101:2102–2112. doi: 10.1053/j.gastro.2010.06.063
7. Berger M, Gray JA, Roth BL. 2009. The expanded biology of serotonin. Annual Review of Medicine 60:355–366. doi: 10.1146/annurev.med.60.042307.110802
8. Bruce-Keller AJ, Salbaum JM, Luo M, Blanchard E, Taylor CM, Welsh DA, Berthoud HR. 2015. Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biological Psychiatry 77:607–615. doi: 10.1016/j.biopsych.2014.07.012
9. Carroll IM, Ringel-Kulka T, Keku TO, Chang YH, Packey CD, Sartor RB, Ringel Y. 2011. Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. American Journal of Physiology. Gastrointestinal and Liver Physiology 301:G799–G807. doi: 10.1152/ajpgi.00154.2011
10. Clemente JC, Pehrsson EC, Blaser MJ, Sandhu K, Gao Z, Wang B, Magris M, Hidalgo G, Contreras M, Noyaalarcón Ó, Lander O, McDonald J, Cox M, Walter J, Oh PL, Ruiz JF, Rodriguez S, Shen N, Song SJ, Metcalf J, et al. 2015. The microbiome of uncontacted amerindians. Science Advances 1:e1500183. doi: 10.1126/sciadv.1500183
11. Collins SM, Surette M, Bercik P. 2012. The interplay between the intestinal microbiota and the brain. Nature Reviews. Microbiology 10:735–742. doi: 10.1038/nrmicro2876
12. Cryan JF, Dinan TG. 2012. Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nature Reviews. Neuroscience 13:701–712. doi: 10.1038/nrn3346
13. Danaceau JP, Chambers EE, Fountain KJ. 2012. Hydrophilic interaction chromatography (HILIC) for LC-MS/MS analysis of monoamine neurotransmitters. Bioanalysis 4:783–794. doi: 10.4155/bio.12.46
14. Daniel H, Moghaddas Gholami A, Berry D, Desmarchelier C, Hahne H, Loh G, Mondot S, Lepage P, Rothballer M, Walker A, Böhm C, Wenning M, Wagner M, Blaut M, Schmitt-Kopplin P, Kuster B, Haller D, Clavel T. 2014. High-fat diet alters gut microbiota physiology in mice. The ISME Journal 8:295–308. doi: 10.1038/ismej.2013.155
15. De Angelis M, Francavilla R, Piccolo M, De Giacomo A, Gobbetti M. 2015. Autism spectrum disorders and intestinal microbiota. Gut Microbes 6:207–213. doi: 10.1080/19490976.2015.1035855
16. De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, Cristofori F, Guerzoni ME, Gobbetti M, Francavilla R. 2013. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PloS One 8:e76993. doi: 10.1371/journal.pone.0076993
17. Desbonnet L, Clarke G, Shanahan F, Dinan TG, Cryan JF. 2014. Microbiota is essential for social development in the mouse. Molecular Psychiatry 19:146–148. doi: 10.1038/mp.2013.65
18. Diaz Heijtz R, Wang S, Anuar F, Qian Y, Bjö rkholm B, Samuelsson A, Hibberd ML, Forssberg H, Pettersson S. 2011. Normal gut microbiota modulates brain development and behavior. Proceedings of the National Academy of Sciences of the United States of America 108:3047–3052. doi: 10.1073/pnas.1010529108
19. Eren AM, Borisy GG, Huse SM, Mark Welch JL. 2014. Pnas plus: From the cover: Oligotyping analysis of the human oral microbiome. Proceedings of the National Academy of Sciences of the United States of America 111:E2875–E2884. doi: 10.1073/pnas.1409644111
20. Feinstein A, Magalhaes S, Richard JF, Audet B, Moore C. 2014. The link between multiple sclerosis and depression. Nature Reviews. Neurology 10:507–517. doi: 10.1038/nrneurol.2014.139
21. Gacias M, Gaspari S, Mae-Santos P, Andrade M, Zhang F, Shen N, Tolstikov N, Kiebish MA, Dupree JL, Zachariou V, Clemente JC, Casaccia P. 2016. Data from: Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior. Dryad Digital Repository. doi: 10.5061/dryad.31v06.2
22. Gevers D, Kugathasan S, Denson LA, Vázquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, Morgan XC, Kostic AD, Luo C, González A, McDonald D, Haberman Y, Walters T, Baker S, Rosh J, Stephens M, et al. 2014. The treatment-naive microbiome in new-onset crohn’s disease. Cell Host & Microbe 15:382–392. doi: 10.1016/j.chom.2014.02.005
23. Gibson EM, Purger D, Mount CW, Goldstein AK, Lin GL, Wood LS, Inema I, Miller SE, Bieri G, Zuchero JB, Barres BA, Woo PJ, Vogel H, Monje M. 2014. Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science 344:1252304. doi: 10.1126/science.1252304
24. Godbout JP, Moreau M, Lestage J, Chen J, Sparkman NL, O’Connor J, Castanon N, Kelley KW, Dantzer R, Johnson RW. 2008. Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system. Neuropsychopharmacology 33:2341–2351. doi: 10.1038/sj.npp.1301649
25. Haberman Y, Tickle TL, Dexheimer PJ, Kim MO, Tang D, Karns R, Baldassano RN, Noe JD, Rosh J, Markowitz J, Heyman MB, Griffiths AM, Crandall WV, Mack DR, Baker SS, Huttenhower C, Keljo DJ, Hyams JS, Kugathasan S, Walters TD, et al. 2014. Pediatric crohn disease patients exhibit specific ileal transcriptome and microbiome signature. The Journal of Clinical Investigation 124:3617–3633. doi: 10.1172/JCI75436
26. Hagemeyer N, Goebbels S, Papiol S, Kästner A, Hofer S, Begemann M, Gerwig UC, Boretius S, Wieser GL, Ronnenberg A, Gurvich A, Heckers SH, Frahm J, Nave KA, Ehrenreich H. 2012. A myelin gene causative of a catatonia-depression syndrome upon aging. EMBO Molecular Medicine 4:528–539. doi: 10.1002/emmm.201200230
27. Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH, Mazmanian SK. 2013. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155:1451–1463. doi: 10.1016/j.cell.2013.11.024
28. 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, Behavior, and Immunity 48:186–194. doi: 10.1016/j.bbi.2015.03.016
29. Katsel P, Davis KL, Haroutunian V. 2005. Variations in myelin and oligodendrocyte-related gene expression across multiple brain regions in schizophrenia: A gene ontology study. Schizophrenia Research 79:157–173. doi: 10.1016/j.schres.2005.06.007
30. Kishi T, Kitajima T, Ikeda M, Yamanouchi Y, Kinoshita Y, Kawashima K, Okochi T, Ozaki N, Iwata N. 2009. Orphan nuclear receptor rev-erb alpha gene (NR1D1) and fluvoxamine response in major depressive disorder in the japanese population. Neuropsychobiology 59:234–238. doi: 10.1159/000226612
31. Krishnan V, Graham A, Mazei-Robison MS, Lagace DC, Kim KS, Birnbaum S, Eisch AJ, Han PL, Storm DR, Zachariou V, Nestler EJ. 2008. Calcium-sensitive adenylyl cyclases in depression and anxiety: Behavioral and biochemical consequences of isoform targeting. Biological Psychiatry 64:336–343. doi: 10.1016/j.biopsych.2008.03.026
32. Landgraf D, McCarthy MJ, Welsh DK. 2014. The role of the circadian clock in animal models of mood disorders. Behavioral Neuroscience 128:344–359. doi: 10.1037/a0036029
33. Lavebratt C, Sjö holm LK, Soronen P, Paunio T, Vawter MP, Bunney WE, Adolfsson R, Forsell Y, Wu JC, Kelsoe JR, Partonen T, Schalling M. 2010. Cry2 is associated with depression. PloS One 5:e9407. doi: 10.1371/journal.pone.0009407
34. Lax S, Smith DP, Hampton-Marcell J, Owens SM, Handley KM, Scott NM, Gibbons SM, Larsen P, Shogan BD, Weiss S, Metcalf JL, Ursell LK, Vázquez-Baeza Y, Van Treuren W, Hasan NA, Gibson MK, Colwell R, Dantas G, Knight R, Gilbert JA. 2014. Longitudinal analysis of microbial interaction between humans and the indoor environment. Science 345:1048–1052. doi: 10.1126/science.1254529
35. Linden JR, Ma Y, Zhao B, Harris JM, Rumah KR, Schaeren-Wiemers N, Vartanian T. 2015. Clostridium perfringens epsilon toxin causes selective death of mature oligodendrocytes and central nervous system demyelination. mBio 6:e02513-14. doi: 10.1128/mBio.02513-14
36. Liu J, Dietz K, DeLoyht JM, Pedre X, Kelkar D, Kaur J, Vialou V, Lobo MK, Dietz DM, Nestler EJ, Dupree J, Casaccia P. 2012. Impaired adult myelination in the prefrontal cortex of socially isolated mice. Nature Neuroscience 15:1621–1623. doi: 10.1038/nn.3263
37. Liu J, Dupree JL, Gacias M, Frawley R, Sikder T, Naik P, Casaccia P. 2016. Clemastine enhances myelination in the prefrontal cortex and rescues behavioral changes in socially isolated mice. The Journal of Neuroscience 36: 957–962. doi: 10.1523/JNEUROSCI.3608-15.2016
38. Liu JJ, Sudic Hukic D, Forsell Y, Schalling M, Ösby U, Lavebratt C. 2015. Depression-associated ARNTL and PER2 genetic variants in psychotic disorders. Chronobiology International 32:579–584. doi: 10.3109/07420528.2015.1012588
39. Lozupone C, Knight R. 2005. Unifrac: A new phylogenetic method for comparing microbial communities. Applied and Environmental Microbiology 71:8228–8235. doi: 10.1128/AEM.71.12.8228-8235.2005
40. Lyte M, Li W, Opitz N, Gaykema RP, Goehler LE. 2006. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia citrobacter rodentium. Physiology & Behavior 89:350–357. doi: 10.1016/j.physbeh.2006.06.019
41. Makinodan M, Rosen KM, Ito S, Corfas G. 2012. A critical period for social experience-dependent oligodendrocyte maturation and myelination. Science 337:1357–1360. doi: 10.1126/science.1220845
42. McKenzie IA, Ohayon D, Li H, de Faria JP, Emery B, Tohyama K, Richardson WD. 2014. Motor skill learning requires active central myelination. Science 346:318–322. doi: 10.1126/science.1254960
43. Moll LT, Gormsen L, Pfeiffer-Jensen M. 2011. [Higher prevalence of depression in patients with rheumatoid arthritis–a systematic review]. Ugeskrift for Laeger 173:2564–2568.
44. Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, Reyes JA, Shah SA, LeLeiko N, Snapper SB, Bousvaros A, Korzenik J, Sands BE, Xavier RJ, Huttenhower C. 2012. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biology 13:R79. doi: 10.1186/gb-2012-13-9-r79
45. Moy SS, Nadler JJ, Young NB, Nonneman RJ, Segall SK, Andrade GM, Crawley JN, Magnuson TR. 2008. Social approach and repetitive behavior in eleven inbred mouse strains. Behavioural Brain Research 191:118–129. doi: 10.1016/j.bbr.2008.03.015
46. Ménard C, Hodes GE, Russo SJ. 2016. Pathogenesis of depression: Insights from human and rodent studies. Neuroscience 321. doi: 10.1016/j.neuroscience.2015.05.053
47. Neufeld KM, Kang N, Bienenstock J, Foster JA. 2011. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterology and Motility 23:e119-255. doi: 10.1111/j.1365-2982.2010.01620.x
48. Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. 2012. Host-gut microbiota metabolic interactions. Science 336:1262–1267. doi: 10.1126/science.1223813
49. Ohara K. 2005. [Omega-3 fatty acids in mood disorders]. Seishin Shinkeigaku Zasshi 107:118–126.
50. Panagiotakos DB, Mamplekou E, Pitsavos C, Kalogeropoulos N, Kastorini CM, Papageorgiou C, Papadimitriou GN, Stefanadis C. 2010. Fatty acids intake and depressive symptomatology in a greek sample: An epidemiological analysis. Journal of the American College of Nutrition 29:586–594 doi: 10.1080/07315724.2010.10719897.
51. Parracho HM, Bingham MO, Gibson GR, McCartney AL. 2005. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. Journal of Medical Microbiology 54:987–991. doi: 10.1099/jmm.0.46101-0
52. Patrick RP, Ames BN. 2015. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: Relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. FASEB Journal 29:2207–2222. doi: 10.1096/fj.14-268342
53. Persico AM, Napolioni V. 2013. Urinary p-cresol in autism spectrum disorder. Neurotoxicology and Teratology 36:82–90. doi: 10.1016/j.ntt.2012.09.002
54. Postal M, Appenzeller S. 2015. The importance of cytokines and autoantibodies in depression. Autoimmunity Reviews 14:30–35. doi: 10.1016/j.autrev.2014.09.001
55. Poudel-Tandukar K, Nanri A, Matsushita Y, Sasaki S, Ohta M, Sato M, Mizoue T. 2009. Dietary intakes of alpha-linolenic and linoleic acids are inversely associated with serum c-reactive protein levels among japanese men. Nutrition Research 29:363–370. doi: 10.1016/j.nutres.2009.05.012
56. Regenold WT, D’Agostino CA, Ramesh N, Hasnain M, Roys S, Gullapalli RP. 2006. Diffusion-weighted magnetic resonance imaging of white matter in bipolar disorder: A pilot study. Bipolar Disorders 8:188–195. doi: 10.1111/j.1399-5618.2006.00281.x
57. Reikvam DH, Erofeev A, Sandvik A, Grcic V, Jahnsen FL, Gaustad P, McCoy KD, Macpherson AJ, Meza-Zepeda LA, Johansen FE. 2011. Depletion of murine intestinal microbiota: Effects on gut mucosa and epithelial gene expression. PloS One 6:e17996. doi: 10.1371/journal.pone.0017996
58. Rumah KR, Linden J, Fischetti VA, Vartanian T. 2013. Isolation of clostridium perfringens type B in an individual at first clinical presentation of multiple sclerosis provides clues for environmental triggers of the disease. PloS One 8:e76359. doi: 10.1371/journal.pone.0076359
59. Rumah KR, Ma Y, Linden JR, Oo ML, Anrather J, Schaeren-Wiemers N, Alonso MA, Fischetti VA, McClain MS, Vartanian T. 2015. The myelin and lymphocyte protein MAL is required for binding and activity of clostridium perfringens e-toxin. PLoS Pathogens 11:e1004896. doi: 10.1371/journal.ppat.1004896
60. Rusielewicz T, Nam J, Damanakis E, John GR, Raine CS, Melendez-Vasquez CV. 2014. Accelerated repair of demyelinated CNS lesions in the absence of non-muscle myosin IIB. Glia 62:580–591. doi: 10.1002/glia.22627
61. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C. 2011. Metagenomic biomarker discovery and explanation. Genome Biology 12:R60. doi: 10.1186/gb-2011-12-6-r60
62. Shalev AY, Freedman S, Peri T, Brandes D, Sahar T, Orr SP, Pitman RK. 1998. Prospective study of posttraumatic stress disorder and depression following trauma. The American Journal of Psychiatry 155:630–637. doi: 10.1176/ajp.155.5.630
63. Shaw W. 2010. Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia. Nutritional Neuroscience 13:135–143. doi: 10.1179/147683010X12611460763968
64. Stratinaki M, Varidaki A, Mitsi V, Ghose S, Magida J, Dias C, Russo SJ, Vialou V, Caldarone BJ, Tamminga CA, Nestler EJ, Zachariou V. 2013. Regulator of G protein signaling 4 [corrected] is a crucial modulator of antidepressant drug action in depression and neuropathic pain models. Proceedings of the National Academy of Sciences of the United States of America 110:8254–8259. doi: 10.1073/pnas.1214696110
65. Sa´nchez MM, Hearn EF, Do D, Rilling JK, Herndon JG. 1998. Differential rearing affects corpus callosum size and cognitive function of rhesus monkeys. Brain Research 812:38–49. doi: 10.1016/S0006-8993(98)00857-9
66. 2 treatment. Microbiology 159:1056–1066. doi: 10.1099/mic.0.063321-0
67. Tkachev D, Mimmack ML, Ryan MM, Wayland M, Freeman T, Jones PB, Starkey M, Webster MJ, Yolken RH, Bahn S. 2003. Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. The Lancet 362:798–805. doi: 10.1016/S0140-6736(03)14289-4
68. Tokita K, Yamaji T, Hashimoto K. 2012. Roles of glutamate signaling in preclinical and/or mechanistic models of depression. Pharmacology Biochemistry and Behavior 100:688–704. doi: 10.1016/j.pbb.2011.04.016
69. Tolstikov V, Nikolayev A, Dong S, Zhao G, Kuo MS. 2014. Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT) inhibition on human cancer cells. PloS One 9:e114019. doi: 10.1371/journal.pone.0114019
70. Trapnell C, Pachter L, Salzberg SL. 2009. Tophat: Discovering splice junctions with rna-seq. Bioinformatics 25: 1105–1111. doi: 10.1093/bioinformatics/btp120
71. Urayama S, Zou W, Brooks K, Tolstikov V. 2010. Comprehensive mass spectrometry based metabolic profiling of blood plasma reveals potent discriminatory classifiers of pancreatic cancer. Rapid Communications in Mass Spectrometry 24:613–620. doi: 10.1002/rcm.4420
72. van Hees NJ, Giltay EJ, Tielemans SM, Geleijnse JM, Puvill T, Janssen N, Does W. 2015. Correction: Essential amino acids in the gluten-free diet and serum in relation to depression in patients with celiac disease. PloS One 10:e0129640. doi: 10.1371/journal.pone.0129640
73. Walker JR, Graff LA, Dutz JP, Bernstein CN. 2011. Psychiatric disorders in patients with immune-mediated inflammatory diseases: Prevalence, association with disease activity, and overall patient well-being. The Journal of Rheumatology. Supplement 88:31–35. doi: 10.3899/jrheum.110900
74. Watkins TA, Emery B, Mulinyawe S, Barres BA. 2008. Distinct stages of myelination regulated by gamma-secretase and astrocytes in a rapidly myelinating CNS coculture system. Neuron 60:555–569. doi: 10.1016/j.neuron.2008.09.011
75. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, Sinha R, Gilroy E, Gupta K, Baldassano R, Nessel L, Li H, Bushman FD, Lewis JD. 2011. Linking long-term dietary patterns with gut microbial enterotypes. Science 334:105–108. doi: 10.1126/science.1208344
76. Wu JY, Roberts E. 1974. Properties of brain l-glutamate decarboxylase: Inhibition studies. Journal of Neurochemistry 23:759–767. doi: 10.1111/j.1471-4159.1974.tb04401.x
77. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY. 2015. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161:264–276. doi: 10.1016/j.cell.2015.02.047
78. Zou W, Tolstikov VV. 2008. Probing genetic algorithms for feature selection in comprehensive metabolic profiling approach. Rapid Communications in Mass Spectrometry 22:1312–1324. doi: 10.1002/rcm.3507