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Impact of Clostridium Bacteria in Children with Autism Spectrum Disorder and Their Anthropometric Measurements

Journal of Molecular Neuroscience volume 70, pages 897–907 (2020)Cite this article

Abstract

Current research has shown that gut microbiota may play a fundamental role in neurological activity, behavior, mood, cognition, and possibly for the onset as well as the severity of autism spectrum disorder (ASD). Previous studies emphasized the possible correlation between Clostridium spp., gut colonization, and possible development or exacerbating of ASD in affected children. The aim of the present study was to investigate how Clostridia gut colonization can have an impact on the neurological outcome and anthropometric values in ASD children. The present study included 60 children (30 ASD and 30 neurotypical controls) of both sexes aged from 2 to 8 years. Children with ASD were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), Autism Diagnostic Interview-Revised (ADI-R), as well as the Childhood Autism Rating Scale (CARS). Quantitative real-time polymerase chain reaction (real-time PCR) was used to determine Clostridium presence in the stools of the enrolled subjects. The number of Clostridium spp. (Clostridium paraputri, Clostridium bolteae, and Clostridium perfringens) found in the stools of ASD children was greater than neurotypical children. Children with ASD had two types of Clostridium (Clostridium diffiicile and Clostridium clostridiioforme) not found in neurotypical children, whereas neurotypical children yielded only one species (Clostridium tertium) not found in the ASD children. The present study emphasizes the potential correlation between gut colonization of Clostridia and the probability of developing or exacerbating ASD among Egyptian children. If Clostridium bacteria play a potential role in the etiology of ASD, this may open the possibility for effective treatment of these patients.

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References

  • 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. https://doi.org/10.1186/1471-230X-11-22

    Article  PubMed  PubMed Central  Google Scholar 

  • Alshammari MK, AlKhulaifi MM, Al Farraj DA, Somily AM, Albarrag AM (2019) Incidence of Clostridium perfringens and its toxin genes in the gut of children with autism spectrum disorder. Anaerobe 61:102114. https://doi.org/10.1016/j.anaerobe.2019.102114

    Article  CAS  PubMed  Google Scholar 

  • APA - American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Press, Washington

    Book  Google Scholar 

  • Argou-Cardozo I, Zeidán-Chuliá F (2018) Clostridium bacteria and autism spectrum conditions: a systematic review and hypothetical contribution of environmental glyphosate levels. Med Sci 6:29. https://doi.org/10.3390/medsci6020029

    Article  CAS  Google Scholar 

  • Azad MB, Konya T, Maughan H, Guttman DS, Field CJ, Chari RS, Sears MR, Becker AB, Scott JA, Kozyrskyj AL, CHILD Study Investigators (2013) Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ 185:385–394

    Article  Google Scholar 

  • Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL (2004) GenBank: update. Nucleic Acids Res 32(Database issue):D23–26. https://doi.org/10.1093/nar/gkh045

    Article  Google Scholar 

  • Borghi E, Vignoli A (2019) Rett syndrome and other neurodevelopmental disorders share common changes in gut microbial community: a descriptive review. Int J Mol Sci 20(17):e4160. https://doi.org/10.3390/ijms20174160

    Article  CAS  PubMed  Google Scholar 

  • Cameron N (1986) The methods of auxological anthropology. In: Falkner F, Tanner JM (eds) Human growth 3 methodology. Plenum Press, New York, pp 3–46

    Google Scholar 

  • Cenit MC, Sanz Y, Codoñer-Franch P (2017) Influence of gut microbiota on neuropsychiatric disorders. World J Gastroenterol 23:5486–5498

    Article  CAS  Google Scholar 

  • Critchfield JW, Van Hemert S, Ash M, Mulder L, Ashwood P (2011) The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterol Res Pract 2011:161358

    Article  Google Scholar 

  • 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(10):e76993. https://doi.org/10.1371/journal.pone.0076993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding HT, Taur Y, Walkup JT (2017) Gut microbiota and autism: key concepts and findings. J Autism Develop Disord 47:480–489

    Article  Google Scholar 

  • El-Ansary A, Bacha AB, Bjørklund G, Al-Orf N, Bhat RS, Moubayed N, Abed K (2018) Probiotic treatment reduces the autistic-like excitation/inhibition imbalance in juvenile hamsters induced by orally administered propionic acid and clindamycin. Metab Brain Dis 33:1155–1164

    Article  CAS  Google Scholar 

  • Emond A, Emmett P, Steer C, Golding J (2010) Feeding symptoms, dietary patterns, and growth in young children with autism spectrum disorders. Pediatrics 126:e337–e342. https://doi.org/10.1542/peds.2009-2391

    Article  PubMed  Google Scholar 

  • Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML, Bolte E, McTeague M, Sandler R, Wexler H, Marlowe EM, Collins MD, Lawson PA, Summanen P, Baysallar M, Tomzynski TJ, Read E, Johnson E, Rolfe R, Nasir P, Shah H, Haake DA, Manning P, Kaul A (2002) Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis 35(Suppl. 1):S6–S16. https://doi.org/10.1086/341914

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Finegold SM, Downes J, Summanen PH (2012) Microbiology of regressive autism. Anaerobe 18:260–262

    Article  CAS  Google Scholar 

  • Finegold SM, Summanen PH, Downes J, Corbett K, Komoriya T (2017) Detection of Clostridium perfringens toxin genes in the gut microbiota of autistic children. Anaerobe 45:133–137

    Article  CAS  Google Scholar 

  • Ghalli I, Salah N, Hussien F, Erfan M, El-Ruby M, Mazen I et al (2008) Egyptian growth curves for infants, children and adolescents. In: Satorio A, Buckler JMH, Marazzi N (eds) Crescere nel mondo. Ferring Publisher, Milan

  • Gondalia SV, Palombo EA, Knowles SR, Cox SB, Meyer D, Austin DW (2012) Molecular characterisation of gastrointestinal microbiota of children with autism (with and without gastrointestinal dysfunction) and their neurotypical siblings. Autism Res 5:419–427

    Article  Google Scholar 

  • Góra B, Gofron Z, Grosiak M, Aptekorz M, Kazek B, Kocelak P, Radosz-Komoniewska H, Chudek J, Martirosian G (2018) Toxin profile of fecal Clostridium perfringens strains isolated from children with autism spectrum disorders. Anaerobe 51:73–77

    Article  Google Scholar 

  • Hiernaux J, Tanner JM (1969) Growth and physical studies in: human biology. A guide to field in methods. In: Weiner JJ, Lourie SA (eds) IBP, London. Blackwell; handbook scientific pub, Oxford

    Google Scholar 

  • Iovene MR, Bombace F, Maresca R, Sapone A, Iardino P, Picardi A, Marotta R, Schiraldi C, Siniscalco D, Serra N (2017) Intestinal dysbiosis and yeast isolation in stool of subjects with autism spectrum disorders. Mycopathologia 182:349–363

    Article  Google Scholar 

  • Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, Khoruts A, Geis E, Maldonado J, McDonough-Means S, Pollard EL, Roux S, Sadowsky MJ, Lipson KS, Sullivan MB, Caporaso JG, Krajmalnik-Brown R (2017) Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open label study. Microbiome 5:10. https://doi.org/10.1186/s40168-016-0225-7

    Article  PubMed  PubMed Central  Google Scholar 

  • Li Q, Han Y, Dy ABC, Hagerman RJ (2017) The gut microbiota and autism spectrum disorders. Front Cell Neurosci 11:120. https://doi.org/10.3389/fncel.2017.00120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maidak BL, Cole JR, Lilburn TG, Parker CT Jr, Saxman PR, Farris RJ, Garrity GM, Olsen GJ, Schmidt TM, Tiedje JM (2001) The RDP-II (Ribosomal Database Project). Nucleic Acids Res 29:173–174

    Article  CAS  Google Scholar 

  • Mangiola F, Ianiro G, Franceschi F, Fagiuoli S, Gasbarrini G, Gasbarrini A (2016) Gut microbiota in autism and mood disorders. World J Gastroenterol 22:361–368

    Article  CAS  Google Scholar 

  • Marí-Bauset S, Llopis-González A, Zazpe I, Mari-Sanchis A, Morales-Suárez-Varela M (2015) Anthropometric measures of Spanish children with autism spectrum disorder. Res Autism Spectr Dis 9:26–33

    Article  Google Scholar 

  • Meguid NA, Kandeel WA, Wakeel KE, El-Nofely AA (2014) Anthropometric assessment of a middle eastern group of autistic children. World J Pediatr 10:318–323

    Article  Google Scholar 

  • Meguid N, Anwar M, Zaki S, Kandeel WA, Ahmed N, Tewfik I (2015) Dietary patterns of children with autism spectrum disorder: a study based in Egypt ID design 2012/DOOEL Skopje. Open Access Maced J Med Sci 3(2):262–267. https://doi.org/10.3889/oamjms.2015.051

    Article  PubMed  PubMed Central  Google Scholar 

  • Navarro F, Liu Y, Rhoads JM (2016) Can probiotics benefit children with autism spectrum disorders? World J Gastroenterol 22:10093–10102

    Article  Google Scholar 

  • Nogay NH, Nahikian-Nelms M (2019) Can we reduce autism-related gastrointestinal and behavior problems by gut microbiota based dietary modulation? A review. Nutr Neurosci 19:1–12

    Article  Google Scholar 

  • 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(Pt 10):987–991

    Article  Google Scholar 

  • Pequegnat B, Monteiro MA (2019) Carbohydrate scaffolds for the study of the autism-associated bacterium. Clostridium Bolteae Curr Med Chem. https://doi.org/10.2174/0929867326666190225164527

    Article  CAS  Google Scholar 

  • Petra AI, Panagiotidou S, Hatziagelaki E, Stewart JM, Conti P, Theoharides TC (2015) Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin Ther 37:984–995

    Article  CAS  Google Scholar 

  • Proctor C, Thiennimitr P, Chattipakorn N, Chattipakorn SC (2017) Diet, gut microbiota and cognition. Metab Brain Dis 32:1–17

    Article  CAS  Google Scholar 

  • Quigley EMM (2017) Microbiota-brain-gut axis and neurodegenerative diseases. Curr Neurol Neurosci Rep 17:94. https://doi.org/10.1007/s11910-017-0802-6

    Article  CAS  PubMed  Google Scholar 

  • Rutter M, Le Couteur A, Lord C (2013) ADI-R: autism diagnostic interview revised. Western Psychological Services, Los Angeles

    Google Scholar 

  • Shaaban SY, El Gendy YG, Mehanna NS, El-Senousy WM, El-Feki HSA, Saad K, El-Asheer OM (2018) The role of probiotics in children with autism spectrum disorder: a prospective, open-label study. Nutr Neurosci 21:676–681. https://doi.org/10.1080/1028415X.2017.1347746

    Article  CAS  PubMed  Google Scholar 

  • Siu MT, Weksberg R (2017) Epigenetics of autism spectrum disorder. Adv Exp Med Biol 978:63–90

    Article  CAS  Google Scholar 

  • Song Y, Liu C, Finegold SM (2004) Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol 70:6459–6465

    Article  CAS  Google Scholar 

  • Srivastava K, Raman M, Bhattacharya A (2016) A study on comparison of anthropometrics of autism spectrum disorder children with normal children. Int J Innova Res Dev 5(6):484–487

    Google Scholar 

  • Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J, Jousson O, Leoncini S, Renzi D, Calabrò A, De Filippo C (2017) New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome 5(1):24. https://doi.org/10.1186/s40168-017-0242-1

    Article  PubMed  PubMed Central  Google Scholar 

  • Sun C, Xia W, Zhao Y, Li N, Zhao D, Wu L (2013) Nutritional status survey of children with autism and typically developing children aged 4–6 years in Heilongjiang Province, China. J Nutr Sci 2:e16. https://doi.org/10.1017/jns.2013.9

    Article  PubMed  PubMed Central  Google Scholar 

  • van De Sande MM, van Buul VJ, Brouns FJ (2014) Autism and nutrition: the role of the gut-brain axis. Nutr Res Rev 27:199–214. https://doi.org/10.1017/S0954422414000110

    Article  CAS  Google Scholar 

  • Vuong HE, Hsiao EY (2017) Emerging roles for the gut microbiome in autism spectrum disorder. Biol Psychiatry 81:411–423. https://doi.org/10.1016/j.biopsych.2016.08.024

    Article  PubMed  Google Scholar 

  • Wang M, Wan J, Rong H, He F, Wang H, Zhou J, Cai C, Wang Y, Xu R, Yin Z, Zhou W (2019) Alterations in gut glutamate metabolism associated with changes in gut microbiota composition in children with autism spectrum disorder. mSystems:4(1). https://doi.org/10.1128/mSystems.00321-18

    Article  CAS  Google Scholar 

  • Wiley NC, Dinan TG, Ross RP, Stanton C, Clarke G, Cryan JF (2017) The microbiota-gut-brain axis as a key regulator of neural function and the stress response: implications for human and animal health. J Anim Sci 95:3225–3246

    CAS  PubMed  Google Scholar 

  • Xiong N, Ji C, Li Y, He Z, Bo H, Zhao Y (2009) The physical status of children with autism in China. Res Dev Disabil 30:70–76

    Article  Google Scholar 

  • Yutin N, Galperin MY (2013) A genomic update on clostridial phylogeny: gram-negative spore formers and other misplaced clostridia. Environ Microbiol 15(10):2631–2641. https://doi.org/10.1111/1462-2920.12173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by the National Research Centre, Cairo, Egypt.

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Authors and Affiliations

  1. Theodor Bilharz Research Institute, Giza, Egypt

    Wafaa A. Kandeel

  2. Research on Children with Special Needs DepartmentNational Research Centre, Giza, Egypt

    Nagwa A. Meguid & Amal Elsaeid

  3. CONEM Egypt Child Brain Research Group, National Research Centre, Giza, Egypt

    Nagwa A. Meguid

  4. Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610, Mo i Rana, Norway

    Geir Bjørklund

  5. Faculty of Postgraduate Childhood Studies, Ain Shams University, Cairo, Egypt

    Ehab M. Eid & Maisa Farid

  6. Biological Anthropology Department, National Research Centre, Giza, Egypt

    Sanaa K. Mohamed, Khaled E. Wakeel & Doaa Y. Hammad

  7. Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy

    Salvatore Chirumbolo

  8. CONEM Scientific Secretary, Verona, Italy

    Salvatore Chirumbolo

Authors
  1. Wafaa A. Kandeel
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  2. Nagwa A. Meguid
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Correspondence to Geir Bjørklund.

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Kandeel, W.A., Meguid, N.A., Bjørklund, G. et al. Impact of Clostridium Bacteria in Children with Autism Spectrum Disorder and Their Anthropometric Measurements. J Mol Neurosci 70, 897–907 (2020). https://doi.org/10.1007/s12031-020-01482-2

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  • DOI: https://doi.org/10.1007/s12031-020-01482-2

Keywords

  • Autism
  • Clostridium
  • Stool
  • Gut microbiota
  • Neurological