Gut microbiota and attention deficit hyperactivity disorder: new perspectives for a challenging condition

European Child and Adolescent Psychiatry

Volumn 26, Issue 9, 2017, Pages 1081-1092

  Cenit, María Carmen ^a,b   Nuevo, Isabel Campillo ^a   Codoñer Franch, Pilar ^b,c   Dinan, Timothy G ^d,e   Sanz, Yolanda ^a  

^a INSTITUTO DE AGROQUÍMICA Y TECNOLOGÍA DE ALIMENTOS CSIC   (Spain)

^b HOSPITAL UNIVERSITARIO DR PESET   (Spain)

^c UNIVERSITY OF VALENCIA   (Spain)

^d UNIVERSITY COLLEGE CORK   (Ireland)

^e UNIVERSITY COLLEGE CORK   (Ireland)

Author keywords

ADHD; Dysbiosis; Gut brain axis; Microbiota

Indexed keywords

ATTENTION DEFICIT DISORDER; BEHAVIOR; BRAIN FUNCTION; CHILD NUTRITION; CORRELATION ANALYSIS; DEVELOPMENTAL DISORDER; DIET; DYSBIOSIS; ENVIRONMENTAL FACTOR; GESTATIONAL AGE; HUMAN; IMMUNOPATHOLOGY; INFANT NUTRITION; INTESTINE FLORA; LIFE STRESS; MATERNAL WELFARE; NONHUMAN; OXIDATIVE STRESS; REVIEW; RISK FACTOR; SYMPTOM; BRAIN; IMMUNOLOGY; MICROBIOLOGY; PATHOPHYSIOLOGY;

ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; BRAIN; GASTROINTESTINAL MICROBIOME; HUMANS;

EID: 85015053081     PISSN: 10188827     EISSN: 1435165X     Source Type: Journal    
DOI: 10.1007/s00787-017-0969-z     Document Type: Review

References (112)

1. Martens G, van Loo K (2007) Genetic and environmental factors in complex neurodevelopmental disorders. Curr Genom 8:429–444
2. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA (2007) The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164:942–948
3. Kooij SJJ et al (2010) European consensus statement on diagnosis and treatment of adult ADHD: the European network adult ADHD. BMC Psychiatry 10:67
4. Trull TJ, Tragesser SL, Solhan M, Schwartz-Mette R (2007) Dimensional models of personality disorder: diagnostic and statistical manual of mental disorders fifth edition and beyond. Curr Opin Psychiatry 20:52–56
5. Larson K, Russ SA, Kahn RS, Halfon N (2011) Patterns of comorbidity, functioning, and service use for US children with ADHD, 2007. Pediatrics 127:462–470
6. Dias TGC et al (2013) Developments and challenges in the diagnosis and treatment of ADHD. Rev Bras Psiquiatr 35:S40–S50
7. Childress AC, Sallee FR (2014) Attention-deficit/hyperactivity disorder with inadequate response to stimulants: approaches to management. CNS Drugs 28:121–129
8. Shyu Y-C et al (2015) Attention-deficit/hyperactivity disorder, methylphenidate use and the risk of developing schizophrenia spectrum disorders: a nationwide population-based study in Taiwan. Schizophr Res 168:161–167
9. Martinez-Raga J, Knecht C, Szerman N, Martinez MI (2013) Risk of serious cardiovascular problems with medications for attention-deficit hyperactivity disorder. CNS Drugs 27:15–30
10. Sprich S, Biederman J, Crawford MH, Mundy E, Faraone SV (2000) Adoptive and biological families of children and adolescents with ADHD. J Am Acad Child Adolesc Psychiatry 39:1432–1437
11. Thapar A, Cooper M, Eyre O, Langley K (2013) Practitioner review: what have we learnt about the causes of ADHD? J Child Psychol Psychiatry 54:3–16
12. Sharma A, Couture J (2014) A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). Ann Pharmacother 48:209–225
13. Banaschewski T, Becker K, Scherag S, Franke B, Coghill D (2010) Molecular genetics of attention-deficit/hyperactivity disorder: an overview. Eur Child Adolesc Psychiatry 19:237–257
14. Dinan TG, Cryan JF (2015) The impact of gut microbiota on brain and behaviour: implications for psychiatry. Curr Opin Clin Nutr Metab Care 18:552–558
15. Borre YE et al (2014) Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. doi:10.1016/j.molmed.2014.05.002
16. Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13:701–712
17. McVey Neufeld K-A, Luczynski P, Seira Oriach C, Dinan TG, Cryan JF (2016) What’s bugging your teen?-The microbiota and adolescent mental health. Neurosci Biobehav Rev. doi:10.1016/j.neubiorev.2016.06.005
18. Luczynski P et al (2016) Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior. Int J Neuropsychopharmacol. 19(8). doi:10.1093/ijnp/pyw020
19. Cryan JF, Dinan TG (2015) More than a gut feeling: the microbiota regulates neurodevelopment and behavior. Neuropsychopharmacology 40:241–242
20. De Palma G et al (2015) Microbiota and host determinants of behavioural phenotype in maternally separated mice. Nat Commun 6:7735
21. Collins SM, Kassam Z, Bercik P (2013) The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications. Curr Opin Microbiol 16:240–245
22. Rogers GB et al (2016) From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry 21:738–748
23. Lyte M (2011) Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. Bioessays 33:574–581
24. Bercik P et al (2011) The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141:599–609 (609.e1–3)
25. Collins SM, Bercik P (2009) The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 136:2003–2014
26. Barrett E, Ross RP, O’Toole PW, Fitzgerald GF, Stanton C (2012) γ-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113:411–417
27. Dinan TG, Stanton C, Cryan JF (2013) Psychobiotics: a novel class of psychotropic. Biol Psychiatry 74:720–726
28. Clarke G et al (2012) A distinct profile of tryptophan metabolism along the kynurenine pathway downstream of toll-like receptor activation in irritable bowel syndrome. Front Pharmacol 3:90
29. O’Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF (2014) Serotonin, tryptophan metabolism and the brain–gut- microbiome axis. Behav Brain Res 277:32–48
30. Maes M, Mihaylova I, Ruyter M De, Kubera M, Bosmans E (2007) The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression—and other conditions characterized by tryptophan depletion induced by inflammation. Neuro Endocrinol Lett 28:826–831
31. Guillemin GJ (2012) Quinolinic acid, the inescapable neurotoxin. FEBS J 279:1356–1365
32. O’ Mahony SM, Clarke G, Dinan TG, Cryan JF (2015) Early life adversity and brain development: is the microbiome a missing piece of the puzzle? Neuroscience. doi:10.1016/j.neuroscience.2015.09.068
33. Clarke G et al (2013) The microbiome-gut–brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18:666–673
34. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG (2008) The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res 43:164–174
35. Foley KA, MacFabe DF, Vaz A, Ossenkopp K-P, Kavaliers M (2014) Sexually dimorphic effects of prenatal exposure to propionic acid and lipopolysaccharide on social behavior in neonatal, adolescent, and adult rats: implications for autism spectrum disorders. Int J Dev Neurosci 39:68–78
36. MacFabe DF et al (2007) Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behav Brain Res 176:149–169
37. Stilling RM, Dinan TG, Cryan JF (2014) Microbial genes, brain and behaviour-epigenetic regulation of the gut–brain axis. Genes Brain Behav 13:69–86
38. Erny D et al (2015) Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 18:965–977
39. Corominas-Roso M et al (2013) Decreased serum levels of brain-derived neurotrophic factor in adults with attention-deficit hyperactivity disorder. Int J Neuropsychopharmacol 1–9. doi:10.1017/S1461145712001629
40. Sucksdorff M et al (2015) Preterm birth and poor fetal growth as risk factors of attention-deficit/hyperactivity disorder. Pediatrics. doi:10.1542/peds.2015-1043
41. Rodriguez A, Bohlin G (2005) Are maternal smoking and stress during pregnancy related to ADHD symptoms in children? J Child Psychol Psychiatry 46:246–254
42. Zijlmans MAC, Korpela K, Riksen-Walraven JM, de Vos WM, de Weerth C (2015) Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology 53:233–245
43. Barrett E et al (2013) The individual-specific and diverse nature of the preterm infant microbiota. Arch Dis Child Fetal Neonatal Ed 98:F334–F340
44. Jakobsson HE et al (2014) Decreased gut microbiota diversity, delayed bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut 63:559–566
45. Grönlund MM, Lehtonen OP, Eerola E, Kero P (1999) Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J Pediatr Gastroenterol Nutr 28:19–25
46. Dominguez-Bello MG et al (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA 107:11971–11975
47. Boksa P, El-Khodor BF (2003) Birth insult interacts with stress at adulthood to alter dopaminergic function in animal models: possible implications for schizophrenia and other disorders. Neurosci Biobehav Rev 27:91–101
48. Curran EA et al (2015) Association between obstetric mode of delivery and autism spectrum disorder: a population-based sibling design study. JAMA psychiatry 72:935–942
49. Curran EA et al (2015) Research review: birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. J Child Psychol Psychiatry 56:500–508
50. Talge NM, Allswede DM, Holzman C (2016) Gestational age at term, delivery circumstance, and their association with childhood attention deficit hyperactivity disorder symptoms. Paediatr Perinat Epidemiol 30:171–180
51. Amiri S, Malek A, Sadegfard M, Abdi S (2012) Pregnancy-related maternal risk factors of attention-deficit hyperactivity disorder: a case-control study. ISRN Pediatr 2012:458064
52. Chu S-M et al (2012) The relationship between attention deficit hyperactivity disorder and premature infants in Taiwanese: a case control study. BMC Psychiatry 12:85
53. Johnson S et al (2016) Antecedents of attention-deficit/hyperactivity disorder symptoms in children born extremely preterm. J Dev Behav Pediatr 37:285–297
54. Becattini S, Taur Y, Pamer EG (2016) Antibiotic-induced changes in the intestinal microbiota and disease. Trends Mol Med 22:458–478
55. Sternbach H, State R (1997) Antibiotics: neuropsychiatric effects and psychotropic interactions. Harv Rev Psychiatry 5:214–226
56. Van den Bergh BRH, Marcoen A (2004) High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8- and 9-year-olds. Child Dev 75:1085–1097
57. Li J, Olsen J, Vestergaard M, Obel C (2010) Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: a nationwide follow-up study in Denmark. Eur Child Adolesc Psychiatry 19:747–753
58. Grizenko N, Shayan YR, Polotskaia A, Ter-Stepanian M, Joober R (2008) Relation of maternal stress during pregnancy to symptom severity and response to treatment in children with ADHD. J Psychiatry Neurosci 33:10–16
59. Culhane JF et al (2001) Maternal stress is associated with bacterial vaginosis in human pregnancy. Matern Child Health J 5:127–134
60. Sudo N et al (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 558:263–275
61. Sterley T-L, Howells FM, Russell VA (2013) Maternal separation increases GABA(A) receptor-mediated modulation of norepinephrine release in the hippocampus of a rat model of ADHD, the spontaneously hypertensive rat. Brain Res 1497:23–31
62. Womersley JS, Hsieh JH, Kellaway LA, Gerhardt GA, Russell VA (2011) Maternal separation affects dopamine transporter function in the spontaneously hypertensive rat: an in vivo electrochemical study. Behav Brain Funct 7:49
63. Sanz Y (2016) Bifidobacteria in Foods: health Effects. Encycl Food Heal 1:388–394
64. Mann JR, McDermott S (2011) Are maternal genitourinary infection and pre-eclampsia associated with ADHD in school-aged children? J Atten Disord 15:667–673
65. Silva D, Colvin L, Hagemann E, Bower C (2014) Environmental risk factors by gender associated with attention-deficit/hyperactivity disorder. Pediatrics 133:e14–e22
66. Hsiao EY et al (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155:1451–1463
67. Derecki NC et al (2010) Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med 207:1067–1080
68. Ceylan MF et al (2014) Increased levels of serum neopterin in attention deficit/hyperactivity disorder (ADHD). J Neuroimmunol. doi:10.1016/j.jneuroim.2014.06.002
69. Rivera HM, Christiansen KJ, Sullivan EL (2015) The role of maternal obesity in the risk of neuropsychiatric disorders. Front Neurosci 9:194
70. Jo H et al (2015) Maternal prepregnancy body mass index and child psychosocial development at 6 years of age. Pediatrics 135:e1198–e1209
71. Rodriguez A et al (2008) Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from three prospective pregnancy cohorts. Int J Obes (Lond) 32:550–557
72. Kang SS, Kurti A, Fair DA, Fryer JD (2014) Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring. J Neuroinflammation 11:156
73. Cabrera-Rubio R et al (2012) The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr 96:544–551
74. Cortese S et al (2015) Association between ADHD and obesity: a systematic review and meta-analysis. Am J Psychiatry appiajp201515020266. doi:10.1176/appi.ajp.2015.15020266
75. Cani PD (2013) Gut microbiota and obesity: lessons from the microbiome. Brief Funct Genom 12:381–387
76. Foster JA, McVey Neufeld K-A (2013) Gut–brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 36:305–312
77. Mimouni-Bloch A et al (2013) Breastfeeding may protect from developing attention-deficit/hyperactivity disorder. Breastfeed Med 8:363–367
78. Park S et al (2014) Protective effect of breastfeeding with regard to children’s behavioral and cognitive problems. Nutr J 13:111
79. David LA et al (2013) Diet rapidly and reproducibly alters the human gut microbiome. Nature. doi:10.1038/nature12820
80. Dash S, Clarke G, Berk M, Jacka FN (2015) The gut microbiome and diet in psychiatry: focus on depression. Curr Opin Psychiatry 28:1–6
81. Psaltopoulou T et al (2013) Mediterranean diet, stroke, cognitive impairment, and depression: a meta-analysis. Ann Neurol 74:580–591
82. Jacka FN et al (2013) Maternal and early postnatal nutrition and mental health of offspring by age 5 years: a prospective cohort study. J Am Acad Child Adolesc Psychiatry 52:1038–1047
83. Konikowska K, Regulska-Ilow B, Rózańska D (2012) The influence of components of diet on the symptoms of ADHD in children. Rocz Państwowego Zakładu Hig 63:127–134
84. Pelsser LM et al (2011) Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial. Lancet 377:494–503
85. Sonuga-Barke EJS et al (2013) Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments. Am J Psychiatry 170:275–289
86. Stulnig TM, Zeyda M (2004) Immunomodulation by polyunsaturated fatty acids: impact on T-cell signaling. Lipids 39:1171–1175
87. Kaliannan K, Wang B, Li X-Y, Kim K-J, Kang JX (2015) A host–microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Sci Rep 5:11276
88. Yu H-N et al (2014) Effects of fish oil with a high content of n-3 polyunsaturated fatty acids on mouse gut microbiota. Arch Med Res 45:195–202
89. Chassaing B et al (2015) Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 519:92–96
90. Hawkey E, Nigg JT (2014) Omega-3 fatty acid and ADHD: blood level analysis and meta-analytic extension of supplementation trials. Clin Psychol Rev 34:496–505
91. Ferreira CF et al (2014) Correlation between n-3 polyunsaturated fatty acids consumption and BDNF peripheral levels in adolescents. Lipids Health Dis 13:44
92. Howard AL et al (2011) ADHD is associated with a ‘Western’ dietary pattern in adolescents. J Atten Disord 15:403–411
93. Freeman MP et al (2006) Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry 67:1954–1967
94. Zhang X-W, Hou W-S, Li M, Tang Z-Y (2015) Omega-3 fatty acids and risk of cognitive decline in the elderly: a meta-analysis of randomized controlled trials. Aging Clin Exp Res. doi:10.1007/s40520-015-0381-9
95. Letenneur L, Proust-Lima C, Le Gouge A, Dartigues JF, Barberger-Gateau P (2007) Flavonoid intake and cognitive decline over a 10-year period. Am J Epidemiol 165:1364–1371
96. Desideri G et al (2012) Benefits in cognitive function, blood pressure, and insulin resistance through cocoa flavanol consumption in elderly subjects with mild cognitive impairment: the cocoa, cognition, and aging (CoCoA) study. Hypertension 60:794–801
97. Dvoráková M et al (2007) Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): modulation by a polyphenolic extract from pine bark (pycnogenol). Nutr Neurosci 10:151–157
98. Selma MV, Espín JC, Tomás-Barberán FA (2009) Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem 57:6485–6501
99. Duda-Chodak A, Tarko T, Satora P, Sroka P (2015) Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review. Eur J Nutr 54:325–341
100. Laparra JM, Sanz Y (2010) Interactions of gut microbiota with functional food components and nutraceuticals. Pharmacol Res 61:219–225
101. McKeown C, Hisle-Gorman E, Eide M, Gorman GH, Nylund CM (2013) Association of constipation and fecal incontinence with attention-deficit/hyperactivity disorder. Pediatrics 132:e1210–e1215
102. Stevens LJ, Kuczek T, Burgess JR, Hurt E, Arnold LE (2011) Dietary sensitivities and ADHD symptoms: thirty-five years of research. Clin Pediatr (Phila) 50:279–293
103. Pärtty A, Kalliomäki M, Wacklin P, Salminen S, Isolauri E (2015) A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial. Pediatr Res 77:823–828
104. Sekirov I, Russell SL, Antunes LCM, Finlay BB (2010) Gut microbiota in health and disease. Physiol Rev 90:859–904
105. Chung H, Kasper DL (2010) Microbiota-stimulated immune mechanisms to maintain gut homeostasis. Curr Opin Immunol 22:455–460
106. Atarashi K, Honda K (2011) Microbiota in autoimmunity and tolerance. Curr Opin Immunol 23:761–768
107. Verlaet AAJ, Noriega DB, Hermans N, Savelkoul HFJ (2014) Nutrition, immunological mechanisms and dietary immunomodulation in ADHD. Eur Child Adolesc Psychiatry 23:519–529
108. Toral M et al (2014) The probiotic Lactobacillus coryniformis CECT5711 reduces the vascular pro-oxidant and pro-inflammatory status in obese mice. Clin Sci 127:33–45
109. Chen L et al (2013) Lactobacillus acidophilus ATCC 4356 attenuates the atherosclerotic progression through modulation of oxidative stress and inflammatory process. Int Immunopharmacol 17:108–115
110. Joseph N, Zhang-James Y, Perl A, Faraone SV (2015) Oxidative stress and ADHD: a meta-analysis. J Atten Disord 19:915–924
111. Kul M et al (2015) Evaluation of oxidative metabolism in child and adolescent patients with attention deficit hyperactivity disorder. Psychiatry Investig 12:361–366
112. Sezen H et al (2016) Increased oxidative stress in children with attention deficit hyperactivity disorder. Redox Rep 21:248–253