DOI QR코드

DOI QR Code

Alteration of Gut Microbiota in Autism Spectrum Disorder: An Overview

  • Oh, Donghun (Department of Psychiatry, Yonsei University College of Medicine) ;
  • Cheon, Keun-Ah (Department of Psychiatry, Yonsei University College of Medicine)
  • Received : 2019.12.03
  • Accepted : 2020.04.16
  • Published : 2020.07.01

Abstract

The microbiota-gut-brain axis, which refers to the bidirectional communication pathway between gut bacteria and the central nervous system, has a profound effect on important brain processes, from the synthesis of neurotransmitters to the modulation of complex behaviors such as sociability and anxiety. Previous studies have revealed that the gut microbiota is potentially related to not only gastrointestinal disturbances, but also social impairment and repetitive behavior-core symptoms of autism spectrum disorder (ASD). Although studies have been conducted to characterize the microbial composition in patients with ASD, the results are heterogeneous. Nevertheless, it is clear that there is a difference in the composition of the gut microbiota between ASD and typically developed individuals, and animal studies have repeatedly suggested that the gut microbiota plays an important role in ASD pathophysiology. This possibility is supported by abnormalities in metabolites produced by the gut microbiota and the association between altered immune responses and the gut microbiota observed in ASD patients. Based on these findings, various attempts have been made to use the microbiota in ASD treatment. The results reported to date suggest that microbiota-based therapies may be effective for ASD, but largescale, well-designed studies are needed to confirm this.

Keywords

References

  1. Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV, Knight R. Current understanding of the human microbiome. Nat Med 2018;24:392-400. https://doi.org/10.1038/nm.4517
  2. Sharon G, Sampson TR, Geschwind DH, Mazmanian SK. The central nervous system and the gut microbiome. Cell 2016;167:915-932. https://doi.org/10.1016/j.cell.2016.10.027
  3. Vuong HE, Hsiao EY. Emerging roles for the gut microbiome in autism spectrum disorder. Biol Psychiatry 2017;81:411-423. https://doi.org/10.1016/j.biopsych.2016.08.024
  4. Vasquez A. Biological plausibility of the gut-brain axis in autism. Ann N Y Acad Sci 2017;1408:5-6. https://doi.org/10.1111/nyas.13516
  5. Sherwin E, Dinan TG, Cryan JF. Recent developments in understanding the role of the gut microbiota in brain health and disease. Ann N Y Acad Sci 2018;1420:5-25. https://doi.org/10.1111/nyas.13416
  6. Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci 2017;20:145-155. https://doi.org/10.1038/nn.4476
  7. Ogbonnaya ES, Clarke G, Shanahan F, Dinan TG, Cryan JF, O'Leary OF. Adult hippocampal neurogenesis is regulated by the microbiome. Biol Psychiatry 2015;78:e7-e9. https://doi.org/10.1016/j.biopsych.2015.04.017
  8. Mohle L, Mattei D, Heimesaat MM, Bereswill S, Fischer A, Alutis M, et al. Ly6Chi monocytes provide a link between antibiotic-induced changes in gut microbiota and adult hippocampal neurogenesis. Cell Rep 2016;15:1945-1956. https://doi.org/10.1016/j.celrep.2016.04.074
  9. Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Toth M, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med 2014;6:263ra158. https://doi.org/10.1126/scitranslmed.3009759
  10. Li Q, Han Y, Dy ABC, Hagerman RJ. The gut microbiota and autism spectrum disorders. Front Cell Neurosci 2017;11:120. https://doi.org/10.3389/fncel.2017.00120
  11. Baio J, Wiggins L, Christensen DL, Maenner MJ, Daniels J, Warren Z, et al. Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2014. MMWR Surveill Summ 2018;67:1-23.
  12. Buescher AV, Cidav Z, Knapp M, Mandell DS. Costs of autism spectrum disorders in the United Kingdom and the United States. JAMA Pediatr 2014;168:721-728. https://doi.org/10.1001/jamapediatrics.2014.210
  13. Fakhoury M. Autistic spectrum disorders: a review of clinical features, theories and diagnosis. Int J Dev Neurosci 2015;43:70-77. https://doi.org/10.1016/j.ijdevneu.2015.04.003
  14. Bik EM. The hoops, hopes, and hypes of human microbiome research. Yale J Biol Med 2016;89:363-373.
  15. Buie T, Campbell DB, Fuchs GJ 3rd, Furuta GT, Levy J, Vandewater J, et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 2010;125 Suppl 1:S1-18. https://doi.org/10.1542/peds.2009-1878C
  16. Wasilewska J, Klukowski M. Gastrointestinal symptoms and autism spectrum disorder: links and risks-a possible new overlap syndrome. Pediatric Health Med Ther 2015;6:153-166. https://doi.org/10.2147/PHMT.S85717
  17. McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics 2014;133:872-883. https://doi.org/10.1542/peds.2013-3995
  18. Niehus R, Lord C. Early medical history of children with autism spectrum disorders. J Dev Behav Pediatr 200;27(2 Suppl):S120-S127. https://doi.org/10.1097/00004703-200604002-00010
  19. Afzal N, Murch S, Thirrupathy K, Berger L, Fagbemi A, Heuschkel R. Constipation with acquired megarectum in children with autism. Pediatrics 2003;112:939-942. https://doi.org/10.1542/peds.112.4.939
  20. Peeters B, Noens I, Philips EM, Kuppens S, Benninga MA. Autism spectrum disorders in children with functional defecation disorders. J Pediatr 2013;163:873-878. https://doi.org/10.1016/j.jpeds.2013.02.028
  21. Mayer EA, Padua D, Tillisch K. Altered brain-gut axis in autism: comorbidity or causative mechanisms? Bioessays 2014;36:933-939. https://doi.org/10.1002/bies.201400075
  22. Fulceri F, Morelli M, Santocchi E, Cena H, Del Bianco T, Narzisi A, et al. Gastrointestinal symptoms and behavioral problems in preschoolers with autism spectrum disorder. Dig Liver Dis 2016;48:248-254. https://doi.org/10.1016/j.dld.2015.11.026
  23. Iovene MR, Bombace F, Maresca R, Sapone A, Iardino P, Picardi A, et al. Intestinal dysbiosis and yeast isolation in stool of subjects with autism spectrum disorders. Mycopathologia 2017;182:349-363. https://doi.org/10.1007/s11046-016-0068-6
  24. Ding HT, Taur Y, Walkup JT. Gut microbiota and autism: key concepts and findings. J Autism Dev Disord 2017;47:480-489. https://doi.org/10.1007/s10803-016-2960-9
  25. Rao M, Gershon MD. The bowel and beyond: the enteric nervous system in neurological disorders. Nat Rev Gastroenterol Hepatol 2016;13:517-528. https://doi.org/10.1038/nrgastro.2016.107
  26. Bernier R, Golzio C, Xiong B, Stessman HA, Coe BP, Penn O, et al. Disruptive CHD8 mutations define a subtype of autism early in development. Cell 2014;158:263-276. https://doi.org/10.1016/j.cell.2014.06.017
  27. Sweatt JD. Pitt-Hopkins syndrome: intellectual disability due to loss of TCF4-regulated gene transcription. Exp Mol Med 2013;45:e21. https://doi.org/10.1038/emm.2013.32
  28. Hosie S, Ellis M, Swaminathan M, Ramalhosa F, Seger GO, Balasuriya GK, et al. G astrointestinal d ysfunction i n p atients a nd mice expressing the autism-associated R451C mutation in neuroligin-3. Autism Res 2019;12:1043-1056. https://doi.org/10.1002/aur.2127
  29. Sharkey KA. Emerging roles for enteric glia in gastrointestinal disorders. J Clin Invest 2015;125:918-925 https://doi.org/10.1172/JCI76303
  30. Grubisic V, Parpura V. The second brain in autism spectrum disorder: could connexin 43 expressed in enteric glial cells play a role? Front Cell Neurosci 2015;9:242.
  31. Walker SJ, Fortunato J, Gonzalez LG, Krigsman A. Identification of unique gene expression profile in children with regressive autism spectrum disorder (ASD) and ileocolitis. PLoS One 2013;8:e58058. https://doi.org/10.1371/journal.pone.0058058
  32. Navarro F, Liu Y, Rhoads JM. Can probiotics benefit children with autism spectrum disorders? World J Gastroenterol 2016;22:10093-10102. https://doi.org/10.3748/wjg.v22.i46.10093
  33. Santocchi E, Guiducci L, Fulceri F, Billeci L, Buzzigoli E, Apicella F, et al. Gut to brain interaction in autism spectrum disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters. BMC Psychiatry 2016;16:183. https://doi.org/10.1186/s12888-016-0887-5
  34. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005;57:67-81. https://doi.org/10.1002/ana.20315
  35. Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 2011;25:40-45. https://doi.org/10.1016/j.bbi.2010.08.003
  36. Onore C, Careaga M, Ashwood P. The role of immune dysfunction in the pathophysiology of autism. Brain Behav Immun 2012;26:383-392. https://doi.org/10.1016/j.bbi.2011.08.007
  37. Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013;155:1451-1463. https://doi.org/10.1016/j.cell.2013.11.024
  38. Fiorentino M, Sapone A, Senger S, Camhi SS, Kadzielski SM, Buie TM, et al. Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism 2016;7:49. https://doi.org/10.1186/s13229-016-0110-z
  39. Esnafoglu E, Cirrik S, Ayyildiz SN, Erdil A, Erturk EY, Dagli A, et al. Increased serum zonulin levels as an intestinal permeability marker in autistic subjects. J Pediatr 2017;188:240-244. https://doi.org/10.1016/j.jpeds.2017.04.004
  40. Morkl S, Lackner S, Meinitzer A, Mangge H, Lehofer M, Halwachs B, et al. Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women. Eur J Nutr 2018;57:2985-2997. https://doi.org/10.1007/s00394-018-1784-0
  41. Williams BL, Hornig M, Buie T, Bauman ML, Cho Paik M, Wick I, et al. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One 2011;6:e24585. https://doi.org/10.1371/journal.pone.0024585
  42. Tomova A, Husarova V, Lakatosova S, Bakos J, Vlkova B, Babinska K, et al. Gastrointestinal microbiota in children with autism in Slovakia. Physiol Behav 2015;138:179-187. https://doi.org/10.1016/j.physbeh.2014.10.033
  43. Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J, et al. New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome 2017;5:24. https://doi.org/10.1186/s40168-017-0242-1
  44. Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML, Bolte E, et al. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis 2002;35:S6-S16. https://doi.org/10.1086/341914
  45. Song Y, Liu C, Finegold SM. Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol 2004;70:6459-6465. https://doi.org/10.1128/AEM.70.11.6459-6465.2004
  46. Alshammari MK, AlKhulaifi MM, Al Farraj DA, Somily AM, Albarrag AM. Incidence of Clostridium perfringens and its toxin genes in the gut of children with autism spectrum disorder. Anaerobe 2020;61:102114. https://doi.org/10.1016/j.anaerobe.2019.102114
  47. De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, et al. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One 2013;8:e76993. https://doi.org/10.1371/journal.pone.0076993
  48. Kang DW, Park JG, Ilhan ZE, Wallstrom G, Labaer J, Adams JB, et al. Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS One 2013;8:e68322. https://doi.org/10.1371/journal.pone.0068322
  49. Rose DR, Yang H, Serena G, Sturgeon C, Ma B, Careaga M, et al. Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms. Brain Behav Immun 2018;70:354-368. https://doi.org/10.1016/j.bbi.2018.03.025
  50. Kang DW, Ilhan ZE, Isern NG, Hoyt DW, Howsmon DP, Shaffer M, et al. Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders. Anaerobe 2018;49:121-131. https://doi.org/10.1016/j.anaerobe.2017.12.007
  51. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol 2005;54:987-991. https://doi.org/10.1099/jmm.0.46101-0
  52. Wang L, Christophersen CT, Sorich MJ, Gerber JP, Angley MT, Conlon MA. Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism. Appl Environ Microbiol 2011;77:6718-6721. https://doi.org/10.1128/AEM.05212-11
  53. Gondalia SV, Palombo EA, Knowles SR, Cox SB, Meyer D, Austin DW. Molecular characterisation of gastrointestinal microbiota of children with autism (with and without gastrointestinal dysfunction) and their neurotypical siblings. Autism Res 2012;5:419-427. https://doi.org/10.1002/aur.1253
  54. Zhao RH, Zheng PY, Liu SM, Tang YC, Li EY, Sun ZY, et al. [Correlation between gut microbiota and behavior symptoms in children with autism spectrum disorder]. Zhongguo Dang Dai Er Ke Za Zhi 2019;21:663-669.
  55. Williams BL, Hornig M, Parekh T, Lipkin WI. Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances. mBio 2012;3:e00261-11.
  56. Kushak RI, Winter HS, Buie TM, Cox SB, Phillips CD, Ward NL. Analysis of the duodenal microbiome in autistic individuals: association with carbohydrate digestion. J Pediatr Gastroenterol Nutr 2017;64:e110-e116. https://doi.org/10.1097/MPG.0000000000001458
  57. Kumar H, Lund R, Laiho A, Lundelin K, Ley RE, Isolauri E, et al. Gut microbiota as an epigenetic regulator: pilot study based on whole-genome methylation analysis. mBio 2014;5:e02113-14.
  58. Srikantha P, Mohajeri MH. The possible role of the microbiotagut-brain-axis in autism spectrum disorder. Int J Mol Sci 2019;20:2115. https://doi.org/10.3390/ijms20092115
  59. Cryan JF, O'Riordan KJ, Sandhu K, Peterson V, Dinan TG. The gut microbiome in neurological disorders. Lancet Neurol 2020;19:179-194. https://doi.org/10.1016/s1474-4422(19)30356-4
  60. Byrne CS, Chambers ES, Morrison DJ, Frost G. The role of short chain fatty acids in appetite regulation and energy homeostasis. Int J Obes (Lond) 2015;39:1331-1338. https://doi.org/10.1038/ijo.2015.84
  61. Stilling RM, Moloney GM, Ryan FJ, Hoban AE, Bastiaanssen TF, Shanahan F, et al. Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice. Elife 2018;7:e33070. https://doi.org/10.7554/elife.33070
  62. Arentsen T, Raith H, Qian Y, Forssberg H, Diaz Heijtz R. Host microbiota modulates development of social preference in mice. Microb Ecol Health Dis 2015;26:29719.
  63. Diaz Heijtz R, Wang S, Anuar F, Qian Y, Bjorkholm B, Samuelsson A, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A 2011;108:3047-3052. https://doi.org/10.1073/pnas.1010529108
  64. Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD, Shanahan F, et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 2013;18:666-673. https://doi.org/10.1038/mp.2012.77
  65. McVey Neufeld KA, Perez-Burgos A, Mao YK, Bienenstock J, Kunze WA. The gut microbiome restores intrinsic and extrinsic nerve function in germ-free mice accompanied by changes in calbindin. Neurogastroenterol Motil 2015;27:627-636. https://doi.org/10.1111/nmo.12534
  66. Desbonnet L, Clarke G, Shanahan F, Dinan TG, Cryan JF. Microbiota is essential for social development in the mouse. Mol Psychiatry 2014;19:146-148. https://doi.org/10.1038/mp.2013.65
  67. Buffington SA, Di Prisco GV, Auchtung TA, Ajami NJ, Petrosino JF, Costa-Mattioli M. Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring. Cell 2016;165:1762-1775. https://doi.org/10.1016/j.cell.2016.06.001
  68. Sharon G, Cruz NJ, Kang DW, Gandal MJ, Wang B, Kim YM, et al. Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice. Cell 2019;177:1600-1618.e17. https://doi.org/10.1016/j.cell.2019.05.004
  69. Stilling RM, Ryan FJ, Hoban AE, Shanahan F, Clarke G, Claesson MJ, et al. Microbes & neurodevelopment--Absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala. Brain Behav Immun 2015;50:209-220. https://doi.org/10.1016/j.bbi.2015.07.009
  70. Aw W, Fukuda S. Toward the comprehensive understanding of the gut ecosystem via metabolomics-based integrated omics approach. Semin Immunopathol 2015;37:5-16. https://doi.org/10.1007/s00281-014-0456-2
  71. Lei E, Vacy K, Boon WC. Fatty acids and their therapeutic potential in neurological disorders. Neurochem Int 2016;95:75-84. https://doi.org/10.1016/j.neuint.2016.02.014
  72. Rose S, Bennuri SC, Murray KF, Buie T, Winter H, Frye RE. Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: a blinded case-control study. PLoS One 2017;12:e0186377. https://doi.org/10.1371/journal.pone.0186377
  73. Cani PD, Knauf C. How gut microbes talk to organs: the role of endocrine and nervous routes. Mol Metab 2016;5:743-752. https://doi.org/10.1016/j.molmet.2016.05.011
  74. Brestoff JR, Artis D. Commensal bacteria at the interface of host metabolism and the immune system. Nat Immunol 2013;14:676-684. https://doi.org/10.1038/ni.2640
  75. Feliz B, Witt DR, Harris BT. Propionic acidemia: a neuropathology case report and review of prior cases. Arch Pathol Lab Med 2003;127:e325-e328. https://doi.org/10.1043/1543-2165(2003)1272.0.CO;2
  76. Al-Owain M, Colak D, Albakheet A, Al-Younes B, Al-Humaidi Z, Al-Sayed M, et al. Clinical and biochemical features associated with BCS1L mutation. J Inherit Metab Dis 2013;36:813-820. https://doi.org/10.1007/s10545-012-9536-4
  77. Frye RE, Rose S, Chacko J, Wynne R, Bennuri SC, Slattery JC, et al. Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines. Transl Psychiatry 2016;6:e927. https://doi.org/10.1038/tp.2016.189
  78. Shultz SR, MacFabe DF, Ossenkopp KP, Scratch S, Whelan J, Taylor R, et al. Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: implications for an animal model of autism. Neuropharmacology 2008;54:901-911. https://doi.org/10.1016/j.neuropharm.2008.01.013
  79. Ossenkopp KP, Foley KA, Gibson J, Fudge MA, Kavaliers M, Cain DP, et al. Systemic treatment with the enteric bacterial fermentation product, propionic acid, produces both conditioned taste avoidance and conditioned place avoidance in rats. Behav Brain Res 2012;227:134-141. https://doi.org/10.1016/j.bbr.2011.10.045
  80. Foley KA, Ossenkopp KP, Kavaliers M, Macfabe DF. Pre- and neonatal exposure to lipopolysaccharide or the enteric metabolite, propionic acid, alters development and behavior in adolescent rats in a sexually dimorphic manner. PLoS One 2014;9:e87072. https://doi.org/10.1371/journal.pone.0087072
  81. Borghi E, Borgo F, Severgnini M, Savini MN, Casiraghi MC, Vignoli A. Rett syndrome: a focus on gut microbiota. Int J Mol Sci 2017;18:344. https://doi.org/10.3390/ijms18020344
  82. Den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 2013;54:2325-2340. https://doi.org/10.1194/jlr.R036012
  83. Hoeppli RE, Wu D, Cook L, Levings MK. T he environment of regulatory T cell biology: cytokines, metabolites, and the microbiome. Front Immunol 2015;6:61. https://doi.org/10.3389/fimmu.2015.00061
  84. Wang G. Human antimicrobial peptides and proteins. Pharmaceuticals (Basel) 2014;7:545-594. https://doi.org/10.3390/ph7050545
  85. Offermanns S, Schwaninger M. Nutritional or pharmacological activation of HCA2 ameliorates neuroinflammation. Trends Mol Med 2015;21:245-255. https://doi.org/10.1016/j.molmed.2015.02.002
  86. Mohajeri MH, La Fata G, Steinert RE, Weber P. Relationship between the gut microbiome and brain function. Nutr Rev 2018;76:481-496. https://doi.org/10.1093/nutrit/nuy009
  87. Abbas AK, Lichtman AH. Basic immunology: functions and disorders of the immune system. Philadelphia: Elsevier Health Scinces Division;2014.
  88. Banks WA, Gray AM, Erickson MA, Salameh TS, Damodarasamy M, Sheibani N, et al. Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinf lammation, and elements of the neurovascular unit. J Neuroinflammation 2015;12:223. https://doi.org/10.1186/s12974-015-0434-1
  89. Kirsten TB, Taricano M, Maiorka PC, Palermo-Neto J, Bernardi MM. Prenatal lipopolysaccharide reduces social behavior in male offspring. Neuroimmunomodulation 2010;17:240-251. https://doi.org/10.1159/000290040
  90. Kirsten TB, Chaves-Kirsten GP, Chaible LM, Silva AC, Martins DO, Britto LR, et al. Hypoactivity of the central dopaminergic system and autistic-like behavior induced by a single early prenatal exposure to lipopolysaccharide. J Neurosci Res 2012;90:1903-1912. https://doi.org/10.1002/jnr.23089
  91. Custodio CS, Mello BSF, Filho AJMC, de Carvalho Lima CN, Cordeiro RC, Miyajima F, et al. Neonatal immune challenge with lipopolysaccharide triggers long-lasting sex- and age-related behavioral and immune/neurotrophic alterations in mice: relevance to autism spectrum disorders. Mol Neurobiol 2018;55:3775-3788.
  92. Carlezon WA Jr, Kim W, Missig G, Finger BC, Landino SM, Alexander AJ, et al. Maternal and early postnatal immune activation produce sex-specific effects on autism-like behaviors and neuroimmune function in mice. Sci Rep 2019;9:1-18.
  93. Calderon-Guzman D, Hernandez-Islas JL, Espitia Vazquez IR, Barragan-Mejia G, Hernandez-Garcia E, Del Angel DS, et al. Effect of toluene and cresols on Na+,K+-ATPase, and serotonin in rat brain. Regul Toxicol Pharmacol 2005;41:1-5. https://doi.org/10.1016/j.yrtph.2004.09.005
  94. Goodhart PJ, DeWolf WE Jr, Kruse LI. Mechanism-based inactivation of dopamine beta-hydroxylase by p-cresol and related alkylphenols. Biochemistry 1987;26:2576-2583. https://doi.org/10.1021/bi00383a025
  95. Selmer T, Andrei PI. p-Hydroxyphenylacetate decarboxylase from Clostridium difficile. A novel glycyl radical enzyme catalysing the formation of p-cresol. Eur J Biochem 2001;268:1363-1372. https://doi.org/10.1046/j.1432-1327.2001.02001.x
  96. Gevi F, Zolla L, Gabriele S, Persico AM. Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism. Mol Autism 2016;7:47. https://doi.org/10.1186/s13229-016-0109-5
  97. Yang Y, Tian J, Yang B. Targeting gut microbiome: a novel and potential therapy for autism. Life Sci 2018;194:111-119. https://doi.org/10.1016/j.lfs.2017.12.027
  98. Altieri L, Neri C, Sacco R, Curatolo P, Benvenuto A, Muratori F, et al. Urinary p-cresol is elevated in small children with severe autism spectrum disorder. Biomarkers 2011;16:252-260. https://doi.org/10.3109/1354750X.2010.548010
  99. Persico AM, Napolioni V. Urinary p-cresol in autism spectrum disorder. Neurotoxicol Teratol 2013;36:82-90. https://doi.org/10.1016/j.ntt.2012.09.002
  100. Homberg JR, Kolk SM, Schubert D. Editorial perspective of the research topic "deciphering serotonin's role in neurodevelopment." Front Cell Neurosci 2013;7:212. https://doi.org/10.3389/fncel.2013.00212
  101. Gershon MD. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes 2013;20:14-21. https://doi.org/10.1097/MED.0b013e32835bc703
  102. Aymard N, Honore P, Carbuccia I. Determination of 5-hydroxytryptamine and tryptophan by liquid chromatography in whole blood. Its interest for the exploration of mental disorders. Prog Neuropsychopharmacol Biol Psychiatry 1994;18:77-86. https://doi.org/10.1016/0278-5846(94)90025-6
  103. Borre YE, Moloney RD, Clarke G, Dinan TG, Cryan JF. The impact of microbiota on brain and behavior: mechanisms & therapeutic potential. Adv Exp Med Biol 2014;817:373-403. https://doi.org/10.1007/978-1-4939-0897-4_17
  104. Kane MJ, Angoa-Perez M, Briggs DI, Sykes CE, Francescutti DM, Rosenberg DR, et al. Mice genetically depleted of brain serotonin display social impairments, communication deficits and repetitive behaviors: possible relevance to autism. PLoS One 2012;7:e48975. https://doi.org/10.1371/journal.pone.0048975
  105. Del'Guidice T, Lemay F, Lemasson M, Levasseur-Moreau J, Manta S, Etievant A, et al. Stimulation of 5-HT2C receptors improves cognitive deficits induced by human tryptophan hydroxylase 2 loss of f u nction mutation. Neu ropsychophar macolog y 2014;39:1125-1134.
  106. Mosienko V, Beis D, Pasqualetti M, Waider J, Matthes S, Qadri F, et al. Life without brain serotonin: reevaluation of serotonin function with mice deficient in brain serotonin synthesis. Behav Brain Res 2015;277:78-88. https://doi.org/10.1016/j.bbr.2014.06.005
  107. Folk GE Jr, Long JP. Serotonin as a neurotransmitter: a review. Comp Biochem Physiol C 1988;91:251-257. https://doi.org/10.1016/0742-8413(88)90193-4
  108. Goldberg J, Anderson GM, Zwaigenbaum L, Hall GB, Nahmias C, Thompson A, et al. Cortical serotonin type-2 receptor density in parents of children with autism spectrum disorders. J Autism Dev Disord 2009;39:97-104. https://doi.org/10.1007/s10803-008-0604-4
  109. Oblak A, Gibbs TT, Blatt GJ. Reduced serotonin receptor subtypes in a limbic and a neocortical region in autism. Autism Res 2013;6:571-583. https://doi.org/10.1002/aur.1317
  110. Reigstad CS, Salmonson CE, Rainey JF 3rd, Szurszewski JH, Linden DR, Sonnenburg JL, et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J 2015;29:1395-1403. https://doi.org/10.1096/fj.14-259598
  111. Wlodarska M, Luo C, Kolde R, d'Hennezel E, Annand JW, Heim CE, et al. Indoleacrylic acid produced by commensal Peptostreptococcus species suppresses inflammation. Cell Host Microbe 2017;22:25-37.e6. https://doi.org/10.1016/j.chom.2017.06.007
  112. Lamas B, Richard ML, Leducq V, Pham HP, Michel ML, Da Costa G, et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med 2016;22:598-605. https://doi.org/10.1038/nm.4102
  113. Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G, Pieraccini G, et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 2013;39:372-385. https://doi.org/10.1016/j.immuni.2013.08.003
  114. Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res 2015;63:1-9. https://doi.org/10.1016/j.jpsychires.2015.02.021
  115. Morgan JT, Chana G, Pardo CA, Achim C, Semendeferi K, Buckwalter J, et al. Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biol Psychiatry 2010;68:368-376. https://doi.org/10.1016/j.biopsych.2010.05.024
  116. Edmonson C, Ziats MN, Rennert OM. Altered glial marker expression in autistic post-mortem prefrontal cortex and cerebellum. Mol Autism 2014;5:3. https://doi.org/10.1186/2040-2392-5-3
  117. Atladottir HO, Thorsen P, Ostergaard L, Schendel DE, Lemcke S, Abdallah M, et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord 2010;40:1423-1430. https://doi.org/10.1007/s10803-010-1006-y
  118. Malkova NV, Yu CZ, Hsiao EY, Moore MJ, Patterson PH. Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain Behav Immun 2012;26:607-616. https://doi.org/10.1016/j.bbi.2012.01.011
  119. Hsiao EY, McBride SW, Chow J, Mazmanian SK, Patterson PH. Modeling an autism risk factor in mice leads to permanent immune dysregulation. Proc Natl Acad Sci U S A 2012;109:12776-12781. https://doi.org/10.1073/pnas.1202556109
  120. Gruol DL. IL-6 regulation of synaptic function in the CNS. Neuropharmacology 2015;96:42-54. https://doi.org/10.1016/j.neuropharm.2014.10.023
  121. Wei H, Zou H, Sheikh AM, Malik M, Dobkin C, Brown WT, et al. IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J Neuroinflammation 2011;8:52. https://doi.org/10.1186/1742-2094-8-52
  122. Wei H, Chadman KK, McCloskey DP, Sheikh AM, Malik M, Brown WT, et al. Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Biochim Biophys Acta 2012;1822:831-842. https://doi.org/10.1016/j.bbadis.2012.01.011
  123. Kirsten TB, Casarin RC, Bernardi MM, Felicio LF. Pioglitazone abolishes autistic-like behaviors via the IL-6 pathway. PLoS One 2018;13:e0197060. https://doi.org/10.1371/journal.pone.0197060
  124. Steinmetz CC, Turrigiano GG. Tumor necrosis factor-${\alpha}$ signaling maintains the ability of cortical synapses to express synaptic scaling. J Neurosci 2010;30:14685-14690. https://doi.org/10.1523/JNEUROSCI.2210-10.2010
  125. Cunningham AJ, Murray CA, O'neill LAJ, Lynch MA, O'connor JJ. Interleukin-$1{\beta}$ (IL-$1{\beta}$) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro. Neurosci Lett 1996;203:17-20. https://doi.org/10.1016/0304-3940(95)12252-4
  126. Chez MG, Dowling T, Patel PB, Khanna P, Kominsky M. Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol 2007;36:361-365. https://doi.org/10.1016/j.pediatrneurol.2007.01.012
  127. Li X, Chauhan A, Sheikh AM, Patil S, Chauhan V, Li XM, et al. Elevated immune response in the brain of autistic patients. J Neuroimmunol 2009;207:111-116. https://doi.org/10.1016/j.jneuroim.2008.12.002
  128. Bellinger FP, Madamba S, Siggins GR. Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus. Brain Res 1993;628:227-234. https://doi.org/10.1016/0006-8993(93)90959-Q
  129. Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J. Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. J Neuroimmunol 2011;232:196-199. https://doi.org/10.1016/j.jneuroim.2010.10.025
  130. Ricci S, Businaro R, Ippoliti F, Lo Vasco VR, Massoni F, Onofri E, et al. Altered cytokine and BDNF levels in autism spectrum disorder. Neurotox Res 2013;24:491-501. https://doi.org/10.1007/s12640-013-9393-4
  131. Erny D, Hrabe de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 2015;18:965-977. https://doi.org/10.1038/nn.4030
  132. Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, et al. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 2011;332:974-977. https://doi.org/10.1126/science.1206095
  133. Grigorenko EL, Han SS, Yrigollen CM, Leng L, Mizue Y, Anderson GM, et al. Macrophage migration inhibitory factor and autism spectrum disorders. Pediatrics 2008;122:e438-e445. https://doi.org/10.1542/peds.2007-3604
  134. Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science 2012;336:1268-1273. https://doi.org/10.1126/science.1223490
  135. Estes ML, McAllister AK. Maternal immune activation: Implications for neuropsychiatric disorders. Science 2016;353:772-777. https://doi.org/10.1126/science.aag3194
  136. Lukens JR, Lammert CR, Frost EL, Bellinger CE. Critical roles for microbiota-mediated regulation of Th17 responses in a maternal immune activation model of autism. J Immunol 2018;200:166.36.
  137. Sherwin E, Sandhu KV, Dinan TG, Cryan JF. May the force be with you: the light and dark sides of the microbiota-gut-brain axis in neuropsychiatry. CNS Drugs 2016;30:1019-1041. https://doi.org/10.1007/s40263-016-0370-3
  138. Bermudez-Brito M, Plaza-Diaz J, Munoz-Quezada S, Gomez-Llorente C, Gil A. Probiotic mechanisms of action. Ann Nutr Metab 2012;61:160-174. https://doi.org/10.1159/000342079
  139. Lim SK, Kwon MS, Lee J, Oh YJ, Jang JY, Lee JH, et al. Weissella cibaria WIKIM28 ameliorates atopic dermatitis-like skin lesions by inducing tolerogenic dendritic cells and regulatory T cells in BALB/c mice. Sci Rep 2017;7:40040. https://doi.org/10.1038/srep40040
  140. Fond G, Boukouaci W, Chevalier G, Regnault A, Eberl G, Hamdani N, et al. The "psychomicrobiotic": targeting microbiota in major psychiatric disorders: a systematic review. Pathol Biol (Paris) 2015;63:35-42. https://doi.org/10.1016/j.patbio.2014.10.003
  141. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res 2008;43:164-174. https://doi.org/10.1016/j.jpsychires.2008.03.009
  142. Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan TG. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 2010;170:1179-1188. https://doi.org/10.1016/j.neuroscience.2010.08.005
  143. Savignac HM, Kiely B, Dinan TG, Cryan JF. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil 2014;26:1615-1627. https://doi.org/10.1111/nmo.12427
  144. Janik R, Thomason LAM, Stanisz AM, Forsythe P, Bienenstock J, Stanisz GJ. Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA, N-acetyl aspartate and glutamate. Neuroimage 2016;125:988-995. https://doi.org/10.1016/j.neuroimage.2015.11.018
  145. Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr 2011;105:755-764. https://doi.org/10.1017/S0007114510004319
  146. Kato-Kataoka A, Nishida K, Takada M, Kawai M, Kikuchi-Hayakawa H, Suda K, et al. Fermented milk containing Lactobacillus casei strain Shirota preserves the diversity of the gut microbiota and relieves abdominal dysfunction in healthy medical students exposed to academic stress. Appl Environ Microbiol 2016;82:3649-3658. https://doi.org/10.1128/AEM.04134-15
  147. Grossi E, Melli S, Dunca D, Terruzzi V. Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics. SAGE Open Med Case Rep 2016;4:2050313X16666231.
  148. Niu M, Li Q, Zhang J, Wen F, Dang W, Duan G, et al. Characterization of intestinal microbiota and probiotics treatment in children with autism spectrum disorders in China. Front Neurol 2019;10:1084. https://doi.org/10.3389/fneur.2019.01084
  149. Vindigni SM, Surawicz CM. Fecal microbiota transplantation. Gastroenterol Clin North Am 2017;46:171-185. https://doi.org/10.1016/j.gtc.2016.09.012
  150. Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013;108:478-498. https://doi.org/10.1038/ajg.2013.4
  151. Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 2015;149:110-118.e4. https://doi.org/10.1053/j.gastro.2015.03.045
  152. Bak SH, Choi HH, Lee J, Kim MH, Lee YH, Kim JS, et al. Fecal microbiota transplantation for refractory Crohn's disease. Intest Res 2017;15:244-248. https://doi.org/10.5217/ir.2017.15.2.244
  153. Johnsen PH, Hilpusch F, Cavanagh JP, Leikanger IS, Kolstad C, Valle PC, et al. Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. Lancet Gastroenterol Hepatol 2018;3:17-24. https://doi.org/10.1016/s2468-1253(17)30338-2
  154. He Z, Cui BT, Zhang T, Li P, Long CY, Ji GZ, et al. Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: the first report. World J Gastroenterol 2017;23:3565-3568. https://doi.org/10.3748/wjg.v23.i19.3565
  155. Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, et al. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 2017;5:10. https://doi.org/10.1186/s40168-016-0225-7
  156. Kang DW, Adams JB, Coleman DM, Pollard EL, Maldonado J, McDonough-Means S, et al. Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci Rep 2019;9:5821. https://doi.org/10.1038/s41598-019-42183-0
  157. Petrof EO, Claud EC, Gloor GB, Allen-Vercoe E. Microbial ecosystems therapeutics: a new paradigm in medicine? Benef Microbes 2013;4:53-65. https://doi.org/10.3920/BM2012.0039
  158. Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 2004;558:263-275. https://doi.org/10.1113/jphysiol.2004.063388
  159. Verdu EF, Bercik P, Verma-Gandhu M, Huang XX, Blennerhassett P, Jackson W, et al. Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Gut 2006;55:182-190. https://doi.org/10.1136/gut.2005.066100
  160. McKernan DP, Fitzgerald P, Dinan TG, Cryan JF. The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat. Neurogastroenterol Motil 2010;22:1029-e268. https://doi.org/10.1111/j.1365-2982.2010.01520.x
  161. Bercik P, Verdu EF, Foster JA, Macri J, Potter M, Huang X, et al. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology 2010;139:2102-2112.e1. https://doi.org/10.1053/j.gastro.2010.06.063
  162. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, 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;108:16050-16055. https://doi.org/10.1073/pnas.1102999108
  163. Bercik P, Park AJ, Sinclair D, Khoshdel A, Lu J, Huang X, et al. The anxiolytic effect of Bifidobacterium longum NCC3001 i nvolves vagal pathways for gut-brain communication. Neurogastroenterol Motil 2011;23:1132-1139. https://doi.org/10.1111/j.1365-2982.2011.01796.x

Cited by

  1. Paving the Way toward Personalized Medicine: Current Advances and Challenges in Multi-OMICS Approach in Autism Spectrum Disorder for Biomarkers Discovery and Patient Stratification vol.11, pp.1, 2020, https://doi.org/10.3390/jpm11010041
  2. Peripheral Immune Dysfunction: A Problem of Central Importance after Spinal Cord Injury vol.10, pp.9, 2021, https://doi.org/10.3390/biology10090928
  3. Impact of Zinc Oxide Nanoparticles on the Composition of Gut Microbiota in Healthy and Autism Spectrum Disorder Children vol.14, pp.19, 2020, https://doi.org/10.3390/ma14195488
  4. Involvement of Intestinal Goblet Cells and Changes in Sodium Glucose Transporters Expression: Possible Therapeutic Targets in Autistic BTBR T+Itpr3tf/J Mice vol.18, pp.21, 2020, https://doi.org/10.3390/ijerph182111328
  5. Dietary Fat Effect on the Gut Microbiome, and Its Role in the Modulation of Gastrointestinal Disorders in Children with Autism Spectrum Disorder vol.13, pp.11, 2020, https://doi.org/10.3390/nu13113818