Skip to main content

Advertisement

SpringerLink
Log in

The Second Brain: Is the Gut Microbiota a Link Between Obesity and Central Nervous System Disorders?

  • Psychological Issues (M Hetherington and V Drapeau, Section Editors)
  • Published:
Current Obesity Reports Aims and scope Submit manuscript

Abstract

The gut-brain axis is a bi-directional integrated system composed by immune, endocrine, and neuronal components by which the gap between the gut microbiota and the brain is significantly impacted. An increasing number of different gut microbial species are now postulated to regulate brain function in health and disease. The westernized diet is hypothesized to be the cause of the current obesity levels in many countries, a major socio-economical health problem. Experimental and epidemiological evidence suggest that the gut microbiota is responsible for significant immunologic, neuronal, and endocrine changes that lead to obesity. We hypothesize that the gut microbiota, and changes associated with diet, affect the gut-brain axis and may possibly contribute to the development of mental illness. In this review, we discuss the links between diet, gut dysbiosis, obesity, and immunologic and neurologic diseases that impact brain function and behavior.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124(4):837–48.

    Article  CAS  PubMed  Google Scholar 

  2. Lederberg J, Mccray A. ‘Ome sweet’ omics—a genealogical treasury of words. The Scientist. 2001;17.

  3. Jiménez E, Marín ML, Martín R, et al. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008;159(3):187–93.

    Article  PubMed  CAS  Google Scholar 

  4. Bäckhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015;17(5):690–703.

    Article  PubMed  CAS  Google Scholar 

  5. Marietta E, Rishi A, Taneja V. Immunogenetic control of the intestinal microbiota. Immunology. 2015;145(3):313–22.

    Article  CAS  PubMed  Google Scholar 

  6. Frank DN, St Amand AL, Feldman RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007;104(34):13780–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Swidsinski A, Loening-Baucke V, Lochs H, et al. Spatial organization of bacterial flora in normal and inflamed intestine: a fluorescence in situ hybridization study in mice. WJG. 2005;11:1131–40.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ochoa-Repáraz J, Kasper LH. Gut microbiome and the risk factors in central nervous system autoimmunity. FEBS Lett. 2014;588(22):4214–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Turnbaugh PJ, Ridaura VK, Faith JJ, et al. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1(6):6ra14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107(33):14691–6.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zimmer J, Lange B, Frick J-S, et al. A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. Eur J Clin Nutr. 2012;66(1):53–60.

    Article  CAS  PubMed  Google Scholar 

  13. Martínez I, Stegen JC, Maldonado-Gómez MX, et al. The gut microbiota of rural Papua New Guineans: composition, diversity patterns, and ecological processes. Cell Rep. 2015;11(4):527–38.

    Article  PubMed  CAS  Google Scholar 

  14. Bach J-F. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002;347(12):911–20.

    Article  PubMed  Google Scholar 

  15. Joscelyn J, Kasper LH. Digesting the emerging role for the gut microbiome in central nervous system demyelination. Mult Scler. 2014;20(12):1553–9.

    Article  PubMed  CAS  Google Scholar 

  16. Clemente JC, Pehrsson EC, Blaser MJ, et al. The microbiome of uncontacted Amerindians. Sci Adv. 2015;1(3):e1500183.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Tilg H, Moschen AR. Food, immunity, and the microbiome. Gastroenterology. 2015;148:1107–19.

    Article  PubMed  Google Scholar 

  18. Riccio P, Rossano R, Liuzzi GM. May diet and dietary supplements improve the wellness of multiple sclerosis patients? A molecular approach. Autoimmune Dis. 2011;2010:249842.

    PubMed  PubMed Central  Google Scholar 

  19. Ghosh S, Molcan E, DeCoffe D, et al. Diets rich in n-6 PUFA induce intestinal microbial dysbiosis in aged mice. Br J Nutr. 2013;110(3):515–23.

    Article  CAS  PubMed  Google Scholar 

  20. Tripathy D, Mohanty P, Dhindsa S, et al. Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Diabetes. 2003;52(12):2882–7.

    Article  CAS  PubMed  Google Scholar 

  21. Theriot CM, Koenigsknecht MJ, Carlson PE, et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat Commun. 2014;5:3114.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Kleinewietfeld M, Manzel A, Titze J, et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature. 2013;496(7446):518–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Coluccia A, Borracci P, Renna G, et al. Developmental omega-3 supplementation improves motor skills in juvenile-adult rats. Int J Dev Neurosci. 2009;27(6):599–605.

    Article  CAS  PubMed  Google Scholar 

  24. Liuzzi GM, Latronico T, Rossano R, et al. Inhibitory effect of polyunsaturated fatty acids on MMP-9 release from microglial cells--implications for complementary multiple sclerosis treatment. Neurochem Res. 2007;32(12):2184–93.

    Article  CAS  PubMed  Google Scholar 

  25. Stefka AT, Feehley T, Tripathi P, et al. Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci U S A. 2014;111:13145–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Li Y, Innocentin S, Withers DR, et al. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell. 2011;147:629–40.

    Article  CAS  PubMed  Google Scholar 

  27. Monteleone I, Rizzo A, Sarra M, et al. Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract. Gastroenterology. 2011;141:237–48, 248 e1.

    Article  CAS  PubMed  Google Scholar 

  28. Oh DY, Talukdar S, Bae EJ, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell. 2010;142:687–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Braniste V, Al-Asmakh M, Kowal C, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014;6(263):263ra158. This work shows that the gut microbiota and metabolites produced by gut microbes affect the integrity of the blood–brain barrier, essential in controlling neuroinflammation.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Kimura I, Ozawa K, Inoue D, et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun. 2013;4:1829.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Noga MJ, Dane A, Shi S, Attali A, et al. Metabolomics of cerebrospinal fluid reveals changes in the central nervous system metabolism in a rat model of multiple sclerosis. Metabolomics. 2012;8(2):253–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mangalam, A. Poisson L, Nemutlu E, et al. Profile of circulatory metabolites in a relapsing-remitting animal model of multiple sclerosis using global metabolomics. J Clin Cell Immunol 2013;4.

  33. Wu, GD, Compher C, Chen EZ, et al. Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut 2014; pii: gutjnl-2014-308209.

  34. Riccio P, Rossano R. Nutrition facts in multiple sclerosis. ASN Neuro. 2015;7(1):1759091414568185.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Ochoa-Repáraz J, Mielcarz DW, Wang Y, et al. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol. 2010;3(5):487–95.

    Article  PubMed  CAS  Google Scholar 

  36. Wang Y, Telesford KM, Ochoa-Reparaz J, et al. An intestinal commensal symbiosis factor controls neuroinflammation via TLR2-mediated CD39 signalling. Nat Commun. 2014;5:4432.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Wang Y, Begum-Haque S, Telesford KM, et al. A commensal bacterial product elicits and modulates migratory capacity of CD39 + CD4 T regulatory subsets in the suppression of neuroinflammation. Gut Microbes. 2014;5(4):552–61.

    Article  PubMed  Google Scholar 

  38. Ochoa-Repáraz J, Mielcarz DW, Ditrio LE, et al. Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide a expression. J Immunol. 2010;185(7):4101–8.

    Article  PubMed  CAS  Google Scholar 

  39. Lee YK, Menezes JS, Umesaki Y, et al. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4615–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lavasani S, Dzhambazov B, Nouri M, et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS ONE. 2010;5(2):e9009.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Ezendam J, de Klerk A, Gremmer ER, et al. Effects of Bifidobacterium animalis administered during lactation on allergic and autoimmune responses in rodents. Clin Exp Immunol. 2008;154(3):424–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Takata K, Kinoshita M, Okuno T, et al. The lactic acid bacterium Pediococcus acidilactici suppresses autoimmune encephalomyelitis by inducing IL-10-producing regulatory T cells. PLoS ONE. 2011;6(11):e27644.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Rezende RM, Oliveira RP, Medeiros SR, et al. Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4 + LAP+ regulatory T cells. J Autoimmun. 2013;40:45–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004;558(Pt 1):263–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Desbonnet L, Garrett L, Clarke G, et al. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010;170(4):1179–88.

    Article  CAS  PubMed  Google Scholar 

  46. Ohland CL, Kish L, Bell H, et al. Effects of Lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome. Psychoneuroendocrinology. 2013;38(9):1738–47.

    Article  CAS  PubMed  Google Scholar 

  47. Bravo JA, Forsythe P, Chew MV, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011;108(38):16050–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Matthews DM, Jenks SM. Ingestion of Mycobacterium vaccae decreases anxiety-related behavior and improves learning in mice. Behav Process. 2013;96:27–35.

    Article  Google Scholar 

  49. Distrutti E, O’Reilly J-A, McDonald C, et al. Modulation of intestinal microbiota by the probiotic VSL#3 resets brain gene expression and ameliorates the age-related deficit in LTP. PLoS ONE. 2014;9(9):e106503.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Gareau MG, Wine E, Rodrigues DM, et al. Bacterial infection causes stress-induced memory dysfunction in mice. Gut. 2011;60(3):307–17.

    Article  PubMed  Google Scholar 

  51. Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155(7):1451–63. This manuscript describes the regulatory effect of bacteroides fragilis in a murine model of autism.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Walker AW, Ince J, Duncan SH, et al. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 2011;5(2):220–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–63. This manuscript demonstrates the rapid effects that diet has in the composition of the gut microbiota.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Vijay-Kumar M, Aitken JD, Carvalho FA, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328(5975):228–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57(6):1470–81.

    Article  CAS  PubMed  Google Scholar 

  56. Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Turnbaugh PJ, Bäckhed F, Fulton L, et al. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3(4):213–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bäckhed F, Manchester JK, Semenkovich CF, et al. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007;104(3):979–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9(5):313–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kassinen A, Krogius-Kurikka L, Mäkivuokko H, et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007;133(1):24–33.

    Article  CAS  PubMed  Google Scholar 

  61. Aguilar-Valles A, Inoue W, Rummel C, et al. Obesity, adipokines and neuroinflammation. Neuropharmacology. 2015;96(Pt A):124–34.

    Article  CAS  PubMed  Google Scholar 

  62. Sanna V, Di Giacomo A, La Cava A, et al. Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses. J Clin Invest. 2003;111(2):241–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Matarese G, Di Giacomo A, Sanna V, et al. Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol. 2001;166(10):5909–16.

    Article  CAS  PubMed  Google Scholar 

  64. Matarese G, Carrieri PB, La Cava A, et al. Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells. Proc Natl Acad Sci U S A. 2005;102(14):5150–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. De Rosa V, Procaccini C, La Cava A, et al. Leptin neutralization interferes with pathogenic T cell autoreactivity in autoimmune encephalomyelitis. J Clin Invest. 2006;116(2):447–55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Baranowska-Bik A, Bik W, Styczynska M, et al. Plasma leptin levels and free leptin index in women with Alzheimer’s disease. Neuropeptides. 2015;52:73–8.

    Article  CAS  PubMed  Google Scholar 

  67. Folch J, Patraca I, Martínez N, et al. The role of leptin in the sporadic form of Alzheimer’s disease. Interactions with the adipokines amylin, ghrelin and the pituitary hormone prolactin. Life Sci. 2015: S0024-3205(15)00258-1.

  68. Castanon N, Luheshi G, Layé S. Role of neuroinflammation in the emotional and cognitive alterations displayed by animal models of obesity. Front Neurosci. 2015;9:229.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Berer K, Mues M, Koutrolos M, et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479(7374):538–41.

    Article  CAS  PubMed  Google Scholar 

  70. Ochoa-Repáraz J, Mielcarz DW, Ditrio LE, et al. Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J Immunol. 2009;183(10):6041–50.

    Article  PubMed  CAS  Google Scholar 

  71. Yokote H, Miyake S, Croxford JL, et al. NKT cell-dependent amelioration of a mouse model of multiple sclerosis by altering gut flora. Am J Pathol. 2008;173(6):1714–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Shapira L, Ayalon S, Brenner T. Effects of porphyromonas gingivalis on the central nervous system: activation of glial cells and exacerbation of experimental autoimmune encephalomyelitis. J Periodontol. 2002;73(5):511–6.

    Article  PubMed  Google Scholar 

  73. Nichols FC, Housley WJ, O’Conor CA, et al. Unique lipids from a common human bacterium represent a new class of Toll-like receptor 2 ligands capable of enhancing autoimmunity. Am J Pathol. 2009;175(6):2430–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A. 2010;107(27):12204–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mazmanian SK, Liu CH, Tzianabos AO, et al. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122(1):107–18.

    Article  CAS  PubMed  Google Scholar 

  76. Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature. 2008;453(7195):620–5.

    Article  CAS  PubMed  Google Scholar 

  77. Johnson JL, Jones MB, Cobb BA. Bacterial capsular polysaccharide prevents the onset of asthma through T-cell activation. Glycobiology. 2015;25(4):368–75.

    Article  PubMed  Google Scholar 

  78. Dasgupta S, Erturk-Hasdemir D, Ochoa-Reparaz J, et al. Plasmacytoid dendritic cells mediate anti-inflammatory responses to a gut commensal molecule via both innate and adaptive mechanisms. Cell Host Microbe. 2014;15(4):413–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Fletcher JM, Lonergan R, Costelloe L, et al. CD39 + Foxp3+ regulatory T cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J Immunol. 2009;183(11):7602–10.

    Article  CAS  PubMed  Google Scholar 

  80. Telesford KM, Yan W, Ochoa-Reparaz J, et al. A commensal symbiotic factor derived from Bacteroides fragilis promotes human CD39(+)Foxp3(+) T cells and Treg function. Gut Microbes. 2015;6(4):234–42.

    Article  PubMed  CAS  Google Scholar 

  81. Cantarel BL, Waubant E, Chehoud C, et al. Gut microbiota in multiple sclerosis: possible influence of immunomodulators. J Investig Med. 2015;63(5):729–34.

    Article  CAS  PubMed  Google Scholar 

  82. Mielcarz DW, Kasper LH. The gut microbiome in multiple sclerosis. Curr Treat Options Neurol. 2015;17(4):344.

    Article  PubMed  Google Scholar 

  83. Nouri M, Bredberg A, Weström B, et al. Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells. PLoS ONE. 2014;9(9):e106335. This work demonstrates that inflammatory CNS demyelinating disease affects directly the intestinal structure, permeability and inflammation, suggesting a bi-directional nature of the gut-brain axis.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. de Vries HE, Kooij G, Frenkel D, et al. Inflammatory events at blood-brain barrier in neuroinflammatory and neurodegenerative disorders: implications for clinical disease. Epilepsia. 2012;53 suppl 6:45–52.

    Article  PubMed  Google Scholar 

  85. Mao Y-K, Kasper DL, Wang B, et al. Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons. Nat Commun. 2013;4:1465. This manuscript shows that gut symbiont products directly interact with the neuronal system.

    Article  PubMed  CAS  Google Scholar 

  86. Yano JM, Yu K, Donaldson GP, Shastri GG, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264–76.

    Article  CAS  PubMed  Google Scholar 

  87. Gonzalez-Rey E, Fernandez-Martin A, Chorny A, et al. Therapeutic effect of vasoactive intestinal peptide on experimental autoimmune encephalomyelitis: down-regulation of inflammatory and autoimmune responses. Am J Pathol. 2006;168(4):1179–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Schéle E, Grahnemo L, Anesten F, et al. The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system. Endocrinology. 2013;154(10):3643–51.

    Article  PubMed  CAS  Google Scholar 

  89. Foster JA, Neufeld K-AM. Gut–brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013;36(5):305–12.

    Article  CAS  PubMed  Google Scholar 

  90. Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci. 2011;12(8):453–66.

    Article  CAS  PubMed  Google Scholar 

  91. Mayer EA, Knight R, Mazmanian SK, et al. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci. 2014;34(46):15490–6.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Kohane IS, McMurry A, Weber G, et al. The co-morbidity burden of children and young adults with autism spectrum disorders. PLoS ONE. 2012;7(4):e33224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Adams JB, Johansen LJ, Powell LD, et al. Gastrointestinal flora and gastrointestinal status in children with autism--comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011;11:22.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Williams BL, Hornig M, Buie T, et al. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS ONE. 2011;6(9):e24585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Finegold SM, Downes J, Summanen PH. Microbiology of regressive autism. Anaerobe. 2012;18(2):260–2.

    Article  CAS  PubMed  Google Scholar 

  96. Kang D-W, Park JG, Ilhan ZE, et al. Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS ONE. 2013;8(7):e68322.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Latta CH, Brothers HM, Wilcock DM. Neuroinflammation in Alzheimer’s disease; a source of heterogeneity and target for personalized therapy. Neuroscience. 2015;302:103–11.

    Article  CAS  PubMed  Google Scholar 

  98. Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388–405.

    Article  CAS  PubMed  Google Scholar 

  99. Lafaye A, Junot C, Ramounet-Le Gall B, et al. Profiling of sulfoconjugates in urine by using precursor ion and neutral loss scans in tandem mass spectrometry. Application to the investigation of heavy metal toxicity in rats. J Mass Spectrom. 2004;39:655–64.

    Article  CAS  PubMed  Google Scholar 

  100. Schmidt MV, Schmidt M, Oitzl MS, et al. The HPA system during the postnatal development of CD1 mice and the effects of maternal deprivation. Brain Res Dev Brain Res. 2002;139(1):39–49.

    Article  CAS  PubMed  Google Scholar 

  101. Crumeyrolle-Arias M, Jaglin M, Bruneau A, et al. Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats. Psychoneuroendocrinology. 2014;42:207–17.

    Article  CAS  PubMed  Google Scholar 

  102. Dinan TG, Cryan JF. Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol Motil. 2013;25(9):713–9.

    Article  CAS  PubMed  Google Scholar 

  103. Ochoa-Reparaz J, Mielcarz DW, Begum-Haque S, et al. Gut, bugs, and brain: role of commensal bacteria in the control of central nervous system disease. Ann Neurol. 2011;69:240–7.

    Article  CAS  PubMed  Google Scholar 

  104. Wang Y, Kasper LH. The role of microbiome in central nervous system disorders. Brain Behav Immun. 2014;38:1–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Bercik P, Park AJ, Sinclair D, et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil. 2011;23(12):1132–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Bercik P, Denou E, Collins J, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011;141(2):599–609. 609.e1-3.

    Article  CAS  PubMed  Google Scholar 

  107. Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13(10):701–12.

    Article  CAS  PubMed  Google Scholar 

  108. Borre YE, O’Keeffe GW, Clarke G, et al. Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. 2014;20(9):509–18.

    Article  PubMed  Google Scholar 

  109. Needham BL, Epel ES, Adler NE, et al. Trajectories of change in obesity and symptoms of depression: the CARDIA study. Am J Public Health. 2010;100(6):1040–6.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Ma J, Xiao L. Obesity and depression in US women: results from the 2005–2006 National Health and Nutritional Examination Survey. Obesity (Silver Spring). 2010;18(2):347–53.

    Article  Google Scholar 

  111. Nagl M, Linde K, Stepan H, et al. Obesity and anxiety during pregnancy and postpartum: a systematic review. J Affect Disord. 2015;186:293–305.

    Article  PubMed  Google Scholar 

  112. Francis H, Stevenson R. The longer-term impacts of western diet on human cognition and the brain. Appetite. 2013;63:119–28.

    Article  PubMed  Google Scholar 

  113. Lin H-Y, Huang C-K, Tai C-M, et al. Psychiatric disorders of patients seeking obesity treatment. BMC Psychiatry. 2013;13:1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Atlantis E, Baker M. Obesity effects on depression: systematic review of epidemiological studies. Int J Obes. 2008;32(6):881–91.

    Article  CAS  Google Scholar 

  115. Bruce-Keller AJ, Salbaum JM, Luo M, et al. Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiatry. 2015;77(7):607–15.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the support of the National MS Society grant CA 1027A1/3 and the National Institutes of Health grants R41 AI110170/AI/NIAID and R56 AI098282/AI/NIAID in the preparation of this manuscript. The authors have licensed patents 8586029 and 8580278 to Symbiotix Biotherapies, and a patent 20140030807 pending.

Author information

Authors and Affiliations

  1. Department of Biology, Eastern Washington University, Cheney, WA, 99004, USA

    Javier Ochoa-Repáraz

  2. Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Hanover, NH, 03755, USA

    Lloyd H. Kasper

Authors
  1. Javier Ochoa-Repáraz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lloyd H. Kasper
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Javier Ochoa-Repáraz.

Ethics declarations

Conflict of Interest

Javier Ochoa-Repáraz and Lloyd H. Kasper declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Psychological Issues

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ochoa-Repáraz, J., Kasper, L.H. The Second Brain: Is the Gut Microbiota a Link Between Obesity and Central Nervous System Disorders?. Curr Obes Rep 5, 51–64 (2016). https://doi.org/10.1007/s13679-016-0191-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13679-016-0191-1

Keywords

Search

Navigation