Gut Microbial Dysbiosis in Indian Children with Autism Spectrum Disorders

Abstract

Autism spectrum disorder (ASD) is a term associated with a group of neurodevelopmental disorders. The etiology of ASD is not yet completely understood; however, a disorder in the gut-brain axis is emerging as a prominent factor leading to autism. To identify the taxonomic composition and markers associated with ASD, we compared the fecal microbiota of 30 ASD children diagnosed using Childhood Autism Rating Scale (CARS) score, DSM-5 approved AIIMS-modified INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD), and Indian Scale for Assessment of Autism (ISAA) tool, with family-matched 24 healthy children from Indian population using next-generation sequencing (NGS) of 16S rRNA gene amplicon. Our study showed prominent dysbiosis in the gut microbiome of ASD children, with higher relative abundances of families Lactobacillaceae, Bifidobacteraceae, and Veillonellaceae, whereas the gut microbiome of healthy children was dominated by the family Prevotellaceae. Comparative meta-analysis with a publicly available dataset from the US population consisting of 20 ASD and 20 healthy control samples from children of similar age, revealed a significantly high abundance of genus Lactobacillus in ASD children from both the populations. The results reveal the microbial dysbiosis and an association of selected Lactobacillus species with the gut microbiome of ASD children.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 1.

    Filipek PA, Accardo PJ, Baranek GT, Cook Jr EH, Dawson G, Gordon B, Gravel JS, Johnson CP, Kallen RJ, Levy SE, Minshew NJ, Ozonoff S, Prizant BM, Rapin I, Rogers SJ, Stone WL, Teplin S, Tuchman RF, Volkmar FR (1999) The screening and diagnosis of autistic spectrum disorders. J Autism Dev Disord 29:439–484

    CAS  Article  Google Scholar 

  2. 2.

    Foster JA, McVey Neufeld KA (2013) Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 36:305–312. https://doi.org/10.1016/j.tins.2013.01.005

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    de Bildt A, Sytema S, Ketelaars C, Kraijer D, Mulder E, Volkmar F, Minderaa R (2004) Interrelationship between Autism Diagnostic Observation Schedule-Generic (ADOS-G), Autism Diagnostic Interview-Revised (ADI-R), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) classification in children and adolescents with mental retardation. J Autism Dev Disord 34:129–137

    Article  Google Scholar 

  4. 4.

    Gotham K, Pickles A, Lord C (2009) Standardizing ADOS scores for a measure of severity in autism spectrum disorders. J Autism Dev Disord 39:693–705. https://doi.org/10.1007/s10803-008-0674-3

    Article  PubMed  Google Scholar 

  5. 5.

    Stone WL, Lee EB, Ashford L, Brissie J, Hepburn SL, Coonrod EE, Weiss BH (1999) Can autism be diagnosed accurately in children under 3 years? J Child Psychol Psychiatry 40:219–226

    CAS  Article  Google Scholar 

  6. 6.

    Regier DA, Kuhl EA, Kupfer DJ (2013) The DSM-5: classification and criteria changes. World Psychiatry 12:92–98. https://doi.org/10.1002/wps.20050

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Kim YS, Leventhal BL, Koh Y-J, Fombonne E, Laska E, Lim E-C, Cheon K-A, Kim S-J, Kim Y-K, Lee H (2011) Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatr 168:904–912

    Article  Google Scholar 

  8. 8.

    Lord C, Schopler E, Revicki D (1982) Sex differences in autism. J Autism Dev Disord 12:317–330

    CAS  Article  Google Scholar 

  9. 9.

    Valicenti-McDermott M, McVICAR K, Rapin I, Wershil BK, Cohen H, Shinnar S (2006) Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease. Journal of Developmental & Behavioral Pediatrics 27: S128-S136

    Article  Google Scholar 

  10. 10.

    Horvath K, Perman JA (2002) Autism and gastrointestinal symptoms. Curr Gastroenterol Rep 4:251–258

    Article  PubMed Central  Google Scholar 

  11. 11.

    Shattuck PT, Seltzer MM, Greenberg JS, Orsmond GI, Bolt D, Kring S, Lounds J, Lord C (2007) Change in autism symptoms and maladaptive behaviors in adolescents and adults with an autism spectrum disorder. J Autism Dev Disord 37:1735–1747

    Article  PubMed Central  Google Scholar 

  12. 12.

    Millward C, Ferriter M, Calver S, Connell-Jones G (2008) Gluten-and casein-free diets for autistic spectrum disorder. Cochrane Database Syst Rev 2

  13. 13.

    Saxena R, Sharma V (2016) A metagenomic insight into the human microbiome: its implications in health and disease https://doi.org/10.1016/B978-0-12-420196-5.00009-5

    Google Scholar 

  14. 14.

    Shetty SA, Marathe NP, Shouche YS (2013) Opportunities and challenges for gut microbiome studies in the Indian population. Microbiome 1:24

    Article  PubMed Central  Google Scholar 

  15. 15.

    Vuong HE, Hsiao EY (2017) Emerging roles for the gut microbiome in autism spectrum disorder. Biol Psychiatry 81:411–423

    Article  PubMed Central  Google Scholar 

  16. 16.

    Buffington SA, Di Prisco GV, Auchtung TA, Ajami NJ, Petrosino JF, Costa-Mattioli M (2016) Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring. Cell 165:1762–1775

    CAS  Article  PubMed Central  Google Scholar 

  17. 17.

    Cryan JF, O’Mahony S (2011) The microbiome-gut-brain axis: from bowel to behavior. Neurogastroenterol Motil 23:187–192

    CAS  Article  PubMed Central  Google Scholar 

  18. 18.

    Gill SR, Pop M, DeBoy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, Gordon JI, Relman DA, Fraser-Liggett CM, Nelson KE (2006) Metagenomic analysis of the human distal gut microbiome. Science 312:1355–1359

    CAS  Article  PubMed Central  Google Scholar 

  19. 19.

    Kinross JM, Darzi AW, Nicholson JK (2011) Gut microbiome-host interactions in health and disease. Genome Med 3:1

    Article  Google Scholar 

  20. 20.

    De Theije CG, Koelink PJ, Korte-Bouws GA, da Silva SL, Korte SM, Olivier B, Garssen J, Kraneveld AD (2014) Intestinal inflammation in a murine model of autism spectrum disorders. Brain Behav Immun 37:240–247

    Article  PubMed Central  Google Scholar 

  21. 21.

    de Theije CG, Wopereis H, Ramadan M, van Eijndthoven T, Lambert J, Knol J, Garssen J, Kraneveld AD, Oozeer R (2014) Altered gut microbiota and activity in a murine model of autism spectrum disorders. Brain Behav Immun 37:197–206

    Article  PubMed Central  Google Scholar 

  22. 22.

    Daley TC (2004) From symptom recognition to diagnosis: children with autism in urban India. Soc Sci Med 58:1323–1335

    Article  PubMed Central  Google Scholar 

  23. 23.

    Bhute S, Pande P, Shetty SA, Shelar R, Mane S, Kumbhare SV, Gawali A, Makhani H, Navandar M, Dhotre D (2016) Molecular characterization and meta-analysis of gut microbial communities illustrate enrichment of Prevotella and Megasphaera in Indian subjects. Front Microbiol 7

  24. 24.

    Kumbhare SV, Kumar H, Chowdhury SP, Dhotre DP, Endo A, Mättö J, Ouwehand AC, Rautava S, Joshi R, Patil NP (2017) A cross-sectional comparative study of gut bacterial community of Indian and Finnish children. Sci Rep 7:10555

    Article  PubMed Central  Google Scholar 

  25. 25.

    Kang D-W, Park JG, Ilhan ZE, Wallstrom G, LaBaer J, Adams JB, Krajmalnik-Brown R (2013) Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS One 8:e68322

    CAS  Article  PubMed Central  Google Scholar 

  26. 26.

    Juneja M, Mishra D, Russell PS, Gulati S, Deshmukh V, Tudu P, Sagar R, Silberberg D, Bhutani VK, Pinto JM (2014) INCLEN diagnostic tool for autism spectrum disorder (INDT-ASD): development and validation. Indian Pediatr 51:359–365

    Article  PubMed Central  Google Scholar 

  27. 27.

    Mukherjee SB, Malhotra MK, Aneja S, Chakraborty S, Deshpande S (2015) Diagnostic accuracy of Indian scale for assessment of autism (ISAA) in children aged 2–9 years. Indian Pediatr 52:212–216

    Article  PubMed Central  Google Scholar 

  28. 28.

    Gulati S, Patel H, Chakrabarty B, Dubey R, Arora N, Pandey R, Paul V, Ramesh K, Anand V, Meena A (2017) Development and validation of AIIMS modified INCLEN diagnostic instrument for epilepsy in children aged 1 month–18 years. Epilepsy Res 130:64–68

    Article  PubMed Central  Google Scholar 

  29. 29.

    Wu L, Wen C, Qin Y, Yin H, Tu Q, Van Nostrand JD, Yuan T, Yuan M, Deng Y, Zhou J (2015) Phasing amplicon sequencing on Illumina Miseq for robust environmental microbial community analysis. BMC Microbiol 15:125

    Article  PubMed Central  Google Scholar 

  30. 30.

    Magoč T, Salzberg SL (2011) FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 27:2957–2963

    Article  PubMed Central  Google Scholar 

  31. 31.

    Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Peña AG, Goodrich JK, Gordon JI (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7:335–336

    CAS  Article  PubMed Central  Google Scholar 

  32. 32.

    DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K, Huber T, Dalevi D, Hu P, Andersen GL (2006) Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol 72:5069–5072

    CAS  Article  PubMed Central  Google Scholar 

  33. 33.

    Liaw A, Wiener M (2002) Classification and regression by randomForest. R News 2:18–22

    Google Scholar 

  34. 34.

    Kursa MB, Rudnicki WR (2010) Feature selection with the Boruta package. Journal

  35. 35.

    Asnicar F, Weingart G, Tickle TL, Huttenhower C, Segata N (2015) Compact graphical representation of phylogenetic data and metadata with GraPhlAn. Peer J 3:e1029

    Article  PubMed Central  Google Scholar 

  36. 36.

    Schopler E, Reichler RJ, DeVellis RF, Daly K (1980) Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). J Autism Dev Disord 10:91–103

    CAS  Article  PubMed Central  Google Scholar 

  37. 37.

    Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J, Jousson O, Leoncini S, Renzi D, Calabrò A (2017) New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome 5:24

    Article  PubMed Central  Google Scholar 

  38. 38.

    Díaz-Uriarte R, De Andres SA (2006) Gene selection and classification of microarray data using random forest. BMC Bioinformatics 7:1

    Article  Google Scholar 

  39. 39.

    Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C (2011) Metagenomic biomarker discovery and explanation. Genome Biol 12:R60. https://doi.org/10.1186/gb-2011-12-6-r60

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Turnbaugh PJ, Gordon JI (2009) The core gut microbiome, energy balance and obesity. J Physiol 587:4153–4158

    CAS  Article  PubMed Central  Google Scholar 

  41. 41.

    Cho I, Blaser MJ (2012) The human microbiome: at the interface of health and disease. Nat Rev Genet 13:260–270. https://doi.org/10.1038/nrg3182

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP (2012) Human gut microbiome viewed across age and geography. Nature 486:222–227

    CAS  Article  PubMed Central  Google Scholar 

  43. 43.

    Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI (2011) Human nutrition, the gut microbiome and the immune system. Nature 474:327–336

    CAS  Article  PubMed Central  Google Scholar 

  44. 44.

    Maji A, Misra R, Dhakan DB, Gupta V, Mahato NK, Saxena R, Mittal P, Thukral N, Sharma E, Singh A (2017) Gut microbiome contributes to impairment of immunity in pulmonary tuberculosis patients by alteration of butyrate and propionate producers. Environ Microbiol 20:402–419. https://doi.org/10.1111/1462-2920.14015

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Horvath K, Papadimitriou JC, Rabsztyn A, Drachenberg C, Tildon JT (1999) Gastrointestinal abnormalities in children with autistic disorder. J Pediatr 135:559–563

    CAS  Article  PubMed Central  Google Scholar 

  46. 46.

    de la Fuente-Nunez C, Meneguetti BT, Franco OL, Lu TK (2017) Neuromicrobiology: how microbes influence the brain. ACS Chem Neurosci 9:141–150. https://doi.org/10.1021/acschemneuro.7b00373

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Kelly JR, Minuto C, Cryan JF, Clarke G, Dinan TG (2017) Cross talk: the microbiota and neurodevelopmental disorders. Front Neurosci 11:490

    Article  PubMed Central  Google Scholar 

  48. 48.

    Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD, Youn E, Summanen PH, Granpeesheh D, Dixon D (2010) Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 16:444–453

    CAS  Article  PubMed Central  Google Scholar 

  49. 49.

    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

    Article  PubMed Central  Google Scholar 

  50. 50.

    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. J Med Microbiol 54:987–991

    Article  PubMed Central  Google Scholar 

  51. 51.

    Wang L, Christophersen CT, Sorich MJ, Gerber JP, Angley MT, Conlon MA (2013) Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder. Mol Autism 4(1):42

    CAS  Article  PubMed Central  Google Scholar 

  52. 52.

    Wang L, Christophersen CT, Sorich MJ, Gerber JP, Angley MT, Conlon MA (2011) Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism. Appl Environ Microbiol 77:6718–6721

    CAS  Article  PubMed Central  Google Scholar 

  53. 53.

    McCarthy MM, Wright CL (2017) Convergence of sex differences and the Neuroimmune system in autism Spectrum disorder. Biol Psychiatry 81:402–410. https://doi.org/10.1016/j.biopsych.2016.10.004

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Bolte S, Ozkara N, Poustka F (2002) Autism spectrum disorders and low body weight: is there really a systematic association? Int J Eat Disord 31:349–351

    Article  PubMed Central  Google Scholar 

  55. 55.

    Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen AS, Pedersen BK, Al-Soud WA, Sorensen SJ, Hansen LH, Jakobsen M (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5:e9085. https://doi.org/10.1371/journal.pone.0009085

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Frank DN, Zhu W, Sartor RB, Li E (2011) Investigating the biological and clinical significance of human dysbioses. Trends Microbiol 19:427–434. https://doi.org/10.1016/j.tim.2011.06.005

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Kassinen A, Krogius-Kurikka L, Makivuokko H, Rinttila T, Paulin L, Corander J, Malinen E, Apajalahti J, Palva A (2007) The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 133:24–33. https://doi.org/10.1053/j.gastro.2007.04.005

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Sampson TR, Mazmanian SK (2015) Control of brain development, function, and behavior by the microbiome. Cell Host Microbe 17:565–576. https://doi.org/10.1016/j.chom.2015.04.011

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Belanche A, Doreau M, Edwards JE, Moorby JM, Pinloche E, Newbold CJ (2012) Shifts in the rumen microbiota due to the type of carbohydrate and level of protein ingested by dairy cattle are associated with changes in rumen fermentation. J Nutr 142:1684–1692. https://doi.org/10.3945/jn.112.159574

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P (2010) 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 107:14691–14696. https://doi.org/10.1073/pnas.1005963107

    Article  PubMed  PubMed Central  Google Scholar 

  61. 61.

    David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505:559–563. https://doi.org/10.1038/nature12820

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Ercolini D, Francavilla R, Vannini L, De Filippis F, Capriati T, Di Cagno R, Iacono G, De Angelis M, Gobbetti M (2015) From an imbalance to a new imbalance: Italian-style gluten-free diet alters the salivary microbiota and metabolome of African celiac children. Sci Rep 5:18571. https://doi.org/10.1038/srep18571

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Bonder MJ, Tigchelaar EF, Cai X, Trynka G, Cenit MC, Hrdlickova B, Zhong H, Vatanen T, Gevers D, Wijmenga C (2016) The influence of a short-term gluten-free diet on the human gut microbiome. Genome Med 8:45

    Article  PubMed Central  Google Scholar 

  64. 64.

    Schiffrin E, Rochat F, Link-Amster H, Aeschlimann J, Donnet-Hughes A (1995) Immunomodulation of human blood cells following the ingestion of lactic acid bacteria. J Dairy Sci 78:491–497

    CAS  Article  PubMed Central  Google Scholar 

  65. 65.

    Matsuzaki T (1998) Immunomodulation by treatment with lactobacillus casei strain Shirota. Int J Food Microbiol 41:133–140

    CAS  Article  PubMed Central  Google Scholar 

  66. 66.

    Vujkovic-Cvijin I, Swainson LA, Chu SN, Ortiz AM, Santee CA, Petriello A, Dunham RM, Fadrosh DW, Lin DL, Faruqi AA (2015) Gut-resident Lactobacillus abundance associates with IDO1 inhibition and Th17 dynamics in SIV-infected macaques. Cell Rep 13:1589–1597

    CAS  Article  PubMed Central  Google Scholar 

  67. 67.

    Veckman V, Miettinen M, Pirhonen J, Sirén J, Matikainen S, Julkunen I (2004) Streptococcus pyogenes and Lactobacillus rhamnosus differentially induce maturation and production of Th1-type cytokines and chemokines in human monocyte-derived dendritic cells. J Leukoc Biol 75:764–771

    CAS  Article  PubMed Central  Google Scholar 

  68. 68.

    O'Hara AM, O'Regan P, Fanning A, O'Mahony C, MacSharry J, Lyons A, Bienenstock J, O'Mahony L, Shanahan F (2006) Functional modulation of human intestinal epithelial cell responses by Bifidobacterium infantis and Lactobacillus salivarius. Immunology 118:202–215

    CAS  Article  PubMed Central  Google Scholar 

  69. 69.

    Molloy CA, Morrow AL, Meinzen-Derr J, Schleifer K, Dienger K, Manning-Courtney P, Altaye M, Wills-Karp M (2006) Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol 172:198–205

    CAS  Article  PubMed Central  Google Scholar 

  70. 70.

    Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J (2011) Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 25:40–45

    CAS  Article  Google Scholar 

  71. 71.

    Marlin BJ, Froemke RC (2017) Oxytocin modulation of neural circuits for social behavior. Dev Neurobiol 77:169–189

    CAS  Article  Google Scholar 

  72. 72.

    Taweechotipatr M, Iyer C, Spinler JK, Versalovic J, Tumwasorn S (2009) Lactobacillus saerimneri and lactobacillus ruminis: novel human-derived probiotic strains with immunomodulatory activities. FEMS Microbiol Lett 293:65–72

    CAS  Article  PubMed Central  Google Scholar 

  73. 73.

    Maslowski KM, Mackay CR (2011) Diet, gut microbiota and immune responses. Nat Immunol 12:5–9

    CAS  Article  Google Scholar 

  74. 74.

    Wang W, Chen L, Zhou R, Wang X, Song L, Huang S, Wang G, Xia B (2014) Increased proportions of Bifidobacterium and the Lactobacillus group and loss of butyrate-producing bacteria in inflammatory bowel disease. J Clin Microbiol 52:398–406

    Article  PubMed Central  Google Scholar 

  75. 75.

    Derrien M, van Hylckama Vlieg JE (2015) Fate, activity, and impact of ingested bacteria within the human gut microbiota. Trends Microbiol 23:354–366

    CAS  Article  Google Scholar 

  76. 76.

    Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA (2011) Gastrointestinal flora and gastrointestinal status in children with autism—comparisons to typical children and correlation with autism severity. BMC Gastroenterol 11:22

    Article  PubMed Central  Google Scholar 

  77. 77.

    Martín R, Miquel S, Benevides L, Bridonneau C, Robert V, Hudault S, Chain F, Berteau O, Azevedo V, Chatel JM (2017) Functional characterization of novel Faecalibacterium prausnitzii strains isolated from healthy volunteers: a step forward in the use of F. prausnitzii as a next-generation probiotic. Front Microbiol 8:1226

    Article  PubMed Central  Google Scholar 

  78. 78.

    Oberc A, Coombes BK (2015) Convergence of external Crohn’s disease risk factors on intestinal bacteria. Front Immunol 6

Download references

Acknowledgements

We thank MHRD, Government of India, Centre for Research on Environment and Sustainable Technologies (CREST) at IISER Bhopal for providing financial support. However, the views expressed in this manuscript are that of the authors alone and no approval of the same, explicit or implicit, by MHRD should be assumed. The sequencing and computational analysis were performed at the NGS Facility and HPC and computing facility, respectively, at IISER Bhopal. JP, AM, DBD, and RS received fellowships from the Central University of Kerala, Centre for Research on Environment and Sustainable Technologies (CREST, IISER Bhopal), UGC (University Grants Commission), and DST-INSPIRE, respectively.

Funding

This work was supported by the intramural funding received from IISER Bhopal, Madhya Pradesh, India, and Central University of Kerala, Kerala, India.

Author information

Affiliations

Authors

Contributions

JP and BM collected the samples. DBD carried out the metagenomic data analysis and all computational and statistical analysis. RS and AM carried out the library preparation and sequencing work. AM, DBD, JP, RS, TG, and VKS drafted the manuscript. MMA and NA performed the diagnosis of all the cases. TG and VKS conceived the work and participated in the design of the study. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Tony Grace or Vineet K. Sharma.

Ethics declarations

The protocols for sample collection, sequencing, and analysis as described in the “Materials and Methods” was conducted in accordance with the approved guidelines by the Institutional Ethical Committee of IISER Bhopal, India.

Competing Interests

The authors declare that they have no competing interests.

Electronic supplementary material

ESM 1

(XLSX 17 kb)

ESM 2

(XLSX 19 kb)

ESM 3

(XLSX 19 kb)

ESM 4

(XLSX 18 kb)

ESM 5

(XLSX 18 kb)

ESM 6

(XLSX 16 kb)

ESM 7

(XLSX 25 kb)

ESM 8

(XLSX 19 kb)

ESM 9

(XLSX 18 kb)

ESM 10

(XLSX 26 kb)

ESM 11

(XLSX 17 kb)

ESM 12

(XLSX 16 kb)

ESM 13

(DOCX 15 kb)

ESM 14

(XLSX 19 kb)

ESM 15

(PDF 939 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Pulikkan, J., Maji, A., Dhakan, D.B. et al. Gut Microbial Dysbiosis in Indian Children with Autism Spectrum Disorders. Microb Ecol 76, 1102–1114 (2018). https://doi.org/10.1007/s00248-018-1176-2

Download citation

Keywords

  • Autism spectrum disorder (ASD)
  • Gut microbial dysbiosis
  • Indian children
  • Gut-brain axis
  • Gastrointestinal symptoms