Associação entre autismo e alterações gastrointestinais: uma revisão sistemática

Conteúdo do artigo principal

Guilherme Nobre Nogueira
Nicole Custódio Porto Silva
Hugo Lorran Souza Costa
Poliana Zago Perondi
Rafaela Fernandes Gonçalves
Gustavo Henrique Tomasi

Resumo

Introdução: A associação entre autismo e distúrbios gastrointestinais tem sido cada vez mais investigada, com estudos sugerindo que crianças com autismo podem ter maior suscetibilidade a problemas intestinais, embora a natureza dessa relação ainda não esteja clara.


Objetivo: Revisar sistematicamente as evidências científicas mais recentes sobre a relação entre transtorno do espectro autista e distúrbios gastrointestinais, visando esclarecer suas implicações para o diagnóstico e tratamento. Método: Foi realizada uma revisão sistemática nas bases de dados BVS, Medline e PubMed, utilizando os descritores "gut microbiota" e "autism". Cinquenta e nove artigos que atenderam aos critérios de inclusão foram selecionados.


Resultado: A análise mostrou variações nos resultados, mas indicou uma possível maior predisposição de crianças com autismo a distúrbios gastrointestinais, embora a relação exata permaneça indefinida. A conexão entre autismo e problemas gastrointestinais é complexa e ainda incerta, destacando a necessidade de mais pesquisas para melhorar a compreensão e o tratamento.


Conclusão: Há evidências de uma relação entre autismo e distúrbios gastrointestinais, mas mais estudos são necessários para esclarecer essa associação e melhorar o manejo clínico do transtorno do espectro autista.

Detalhes do artigo

Seção
Artigo de Revisão

Referências

Alamoudi MU, Hosie S, Shindler AE, Wood JL, Franks AE, Hill-Yardin EL.. Comparing the gut microbiome in autism and preclinical models: a systematic review. Front Cell Infect Microbiol. 2022;12:905841. https://doi.org/10.3389/fcimb.2022.905841c

Alharthi A, Alhazmi S, Alburae N, Bahieldin A. The human gut microbiome as a potential factor in autism spectrum disorder. Int J Mol Sci. 2022;23(3):1363. https://doi.org/10.3390/ijms23031363

Andreo-Martínez P, Rubio-Aparicio M, Sánchez-Meca J, Veas A, Martínez-González AE. A meta-analysis of gut microbiota in children with autism. J Autism Dev Disord. 2022;1374–87. Disponível em: https://doi.org/10.1007/s10803-021-05002-y

Bezawada N, Phang TH, Hold G, Hansen R. Autism spectrum disorder and the gut microbiota in children: a systematic review. Ann Nutr Metab. 2020:76(1):16-29. https://doi.org/10.1159/000505363

Cao X, Liu K, Liu J, Liu YW, Xu L, Wang H, et al. Dysbiotic gut microbiota and dysregulation of cytokine profile in children and teens with autism spectrum disorder. Front Neurosci. 2021;635925. https://doi.org/10.3389/fnins.2021.635925

Carissimi C, Laudadio I, Palone F, Fulci V, Cesi V, Cardona F, et al. Functional analysis of gut microbiota and immunoinflammation in children with autism spectrum disorders. Dig Liver Dis. 2019;1366–74. https://doi.org/10.1016/j.dld.2019.06.006

Chen YC, Lin HY, Chien Y, Tung YH, Ni YH, Gau SSF. Altered gut microbiota correlates with behavioral problems but not gastrointestinal symptoms in individuals with autism. Brain Behav Immun. 2022;161–78. https://doi.org/10.1016/j.bbi.2022.08.015

Chernikova MA, Flores GD, Kilroy E, Labus JS, Mayer EA, Aziz-Zadeh L. The brain-gut-microbiome system: pathways and implications for autism spectrum disorder. Nutrients. 2021;13(12):4497. https://doi.org/10.3390/nu13124497

Coretti L, Pararo L, Riccio MP, Amato F, Cuomo M, Natale A, et al. Gut microbiota features in young children with autism spectrum disorders. Front Microbiol. 2018;3146. https://doi.org/10.3389/fmicb.2018.03146

Dan Z, Mao X, Liu Q, Guo M, Zhuang Y, Liu Z, et al. Altered gut microbial profile is associated with abnormal metabolism activity of autism spectrum disorder. Gut Microbes. 2020;11(5):1246–67. https://doi.org/10.1080/19490976.2020.1747329

Deng W, Wang S, Li F, Wang F, Xing YP, Li Y, et al. Gastrointestinal symptoms have a minor impact on autism spectrum disorder and associations with gut microbiota and short-chain fatty acids. Front Microbiol. 2022;1000419. https://doi.org/10.3389/fmicb.2022.1000419

Ding H, Yi X, Zhang X, Wang H, Liu H, Mou WW. Imbalance in the gut microbiota of children with autism spectrum disorders. Front Cell Infect Microbiol. 2021;11:572752. https://doi.org/10.3389/fcimb.2021.572752

Ding X, Xu Y, Zhang X, Zhang L, Duan G, Song C, et al. Gut microbiota changes in patients with autism spectrum disorders. J Psychiatr Res. 2020;129:149–59. https://doi.org/10.1016/j.jpsychires.2020.06.032

Fattorusso A, Genova LD, Dell’Isola GB, Mencaroni E, Esposito S. Autism spectrum disorders and the gut microbiota. Nutrients. 2019;11(3):521. https://doi.org/10.3390/nu11030521

Fujishiro S, Tsuji S, Akagawa S, Akagawa Y, Yamanouchi S, Ishizaki Y, et al. Dysbiosis in gut microbiota in children born preterm who developed autism spectrum disorder: a pilot study. J Autism Dev Disord. 2022;53(10):4012-20. https://doi.org/10.1007/s10803-022-05682-0

Garcia-Gutierrez E, Narbad A, Rodríguez JM. Autism spectrum disorder associated with gut microbiota at immune, metabolomic, and neuroactive level. Front Neurosci. 2020;14:578666. https://doi.org/10.3389/fnins.2020.578666

Góralczyk-Bińkowska A, Szmajda-Krygier D, Kozłowska E. The microbiota–gut–brain axis in psychiatric disorders. Int J Mol Sci. 2022;23(19):11245. https://doi.org/10.3390/ijms231911245

Ha S, Oh D, Lee S, Park J, Ahn J, Choi S, Cheon KA. Altered gut microbiota in Korean children with autism spectrum disorders. Nutrients. 2021;13(10):3300. https://doi.org/10.3390/nu13103300

Hu T, Dong Y, He C, Zhao M, He Q. The gut microbiota and oxidative stress in autism spectrum disorders (ASD). Oxid Med Cell Longev. 2020;2020:8396708. https://doi.org/10.1155/2020/8396708

Hughes HK, Rose D, Ashwood P. The gut microbiota and dysbiosis in autism spectrum disorders. Curr Neurol Neurosci Rep. 2018;18(11):81. https://doi.org/10.1007/s11910-018-0887-6

Iglesias-Vázquez L, Riba GVG, Arija V, Canals J. Composition of gut microbiota in children with autism spectrum disorder: a systematic review and meta-analysis. Nutrients. 2020;12(3):792. https://doi.org/10.3390/nu12030792

Kang DW, Adams JB, Vargason T, Santiago M, Hahn J, Krajmalnik-Brown B. Distinct fecal and plasma metabolites in children with autism spectrum disorders and their modulation after microbiota transfer therapy. MSphere. 2020;5(5):e00314-20. https://doi.org/10.1128/msphere.00314-20

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(1)5821. https://doi.org/10.1038/s41598-019-42183-0

Lasheras I, Seral P, Latorre E, Barroso E, Gracia-García P, Santabárbara J. Microbiota and gut-brain axis dysfunction in autism spectrum disorder: evidence for functional gastrointestinal disorders. Asian J Psychiatr. 2020;47:101874. https://doi.org/10.1016/j.ajp.2019.101874

Li J, Wang H, Qing W, Liu F, Zeng N, Wu F, et al. Congenitally underdeveloped intestine drives autism-related gut microbiota and behavior. Brain Behav Immun. 2022;15–26. https://doi.org/10.1016/j.bbi.2022.06.006

Li Q, Liang J, Fu N, Han Y, Qin J. A ketogenic diet and the treatment of autism spectrum disorder. Front Pediatr. 2021;9:650624. https://doi.org/10.3389/fped.2021.650624.

Liu J, Gao Z, Liu C, Liu T, Gao J, Cai Y, et al. Alteration of gut microbiota: new strategy for treating autism spectrum disorder. Front Cell Dev Biol. 2022;10:792490. https://doi.org/10.3389/fcell.2022.792490

Liu S, Li E, Sun Z, Fu D, Duan G, Jiang M, et al. Altered gut microbiota and short chain fatty acids in Chinese children with autism spectrum disorder. Sci Rep. 2019;9(1):287. https://doi.org/10.1038/s41598-018-36430-z

Liu Z, Mao X, Dan Z, Pei Y, Xu R, Guo M, et al. Gene variations in autism spectrum disorder are associated with alteration of gut microbiota, metabolites and cytokines. Gut Microbes. 2021;13(1):1–16. https://doi.org/10.1080/19490976.2020.1854967.

Lombardi M, Troisi J. Gut reactions: how far are we from understanding and manipulating the microbiota complexity and the interaction with its host? Lessons from autism spectrum disorder studies. Nutrients. 2021;13(10):3492. https://doi.org/10.3390/nu13103492

Lou M, Cao A, Jin C, Mi K, Xiong X, Zeng Z, et al. Deviated and early unsustainable stunted development of gut microbiota in children with autism spectrum disorder. Gut. 2022;71(8):1588–99. https://doi.org/10.1136/gutjnl-2021-325115

Lu C, Rong J, Fu C, Wang W, Xu J, Ju XD. Overall rebalancing of gut microbiota is key to autism intervention. Front Psychol. 2022;13:862719. https://doi.org/10.3389/fpsyg.2022.862719

Lungba RM, Khan SZA, Ajibawo-Aganbi U, Bastidas MVP, Veliginti S, Saleem S, et al. The role of the gut microbiota and the immune system in the development of autism. Cureus. 2020;12(10):e11226. https://doi.org/10.7759/cureus.11226

Madra M, Ringel R, Margolis KG. Gastrointestinal issues and autism spectrum disorder. Child Adolesc Psychiatr Clin N Am. 2020;29(3):501–13. https://doi.org/10.1016/j.chc.2020.02.005

Mehra A, Arora G, Sahni G, Kaur M, Singh H, Singh B, et al. Gut microbiota and autism spectrum disorder: from pathogenesis to potential therapeutic perspectives. J Tradit Complement Med. 2022;13(2):135-49. https://doi.org/10.1016/j.jtcme.2022.03.001

Mohamadkhani A. Gut microbiota and fecal metabolome perturbation in children with autism spectrum disorder. Middle East J Dig Dis. 2018;10(4):205–12. https://doi.org/10.15171/mejdd.2018.112

Moradi K, Ashraf-Ganjouei A, Tavolinejad H, Bagheri S, Akhondzadeh S. The interplay between gut microbiota and autism spectrum disorders: a focus on immunological pathways. Prog Neuropsychopharmacol Biol Psychiatry. 2021;106:110091. https://doi.org/10.1016/j.pnpbp.2020.110091

Nitschke A, Deonandan R, Konkle AT. The link between autism spectrum disorder and gut microbiota: a scoping review. Autism. 2020;24(6):1328–44. https://doi.org/10.1177/1362361320913364

Nogay NH, Nahikian-Nelms M. Can we reduce autism-related gastrointestinal and behavior problems by gut microbiota based dietary modulation? A review. Nutr Neurosci. 2021;24(5):327–38. https://doi.org/10.1080/1028415x.2019.1630894

Oh D, Cheon KA. Alteration of gut microbiota in autism spectrum disorder: an overview. Soa Chongsonyon Chongsin Uihak. 2020;31(3):131–45. https://doi.org/10.5765/jkacap.190039

Peralta-Marzal LN, Prince N, Bajic D, Roussin L, Naudon L, Rabot S, et al. The impact of gut microbiota-derived metabolites in autism spectrum disorders. Int J Mol Sci. 2021. https://doi.org/10.3390/ijms221810052

Plaza-Diaz J, Radar AM, Baig AT, Leyba MF, Costabel MM, Zavala-Crichton JP, et al. Physical activity, gut microbiota, and genetic background for children and adolescents with autism spectrum disorder. Children (Basel). 2022;9(12):1834. https://doi.org/10.3390/children9121834

Prosperi M, Santocchi E, Guiducci L, Frinzi J, Morales MA, Tancredi R, et al. Interventions on microbiota: where do we stand on a gut-brain link in autism? A systematic review. Nutrients. 2022;14(3):462. https://doi.org/10.3390/nu14030462

Ristori MV, Quagliariello A, Reddel S, Laniro G, Vicari S, Gasbarrini A, et al. Autism, gastrointestinal symptoms and modulation of gut microbiota by nutritional interventions. Nutrients. 2019;11(11):2812. https://doi.org/10.3390/nu11112812

Roussin L, Prince N, Perez-Pardo P, Kraneveld AD, Rabot S, Naudon L. Role of the gut microbiota in the pathophysiology of autism spectrum disorder: clinical and preclinical evidence. Microorganisms. 2020;8(9):1369. https://doi.org/10.3390/microorganisms8091369

Saurman V, Margolis KG, Luna RA. Autism spectrum disorder as a brain-gut-microbiome axis disorder. Dig Dis Sci. 2020;65(3):818–28. https://doi.org/10.1007/s10620-020-06133-5

Settanni CR, Bibbò S, Laniro G, Rinninella E, Cintoni M, Mele MC, et al. Gastrointestinal involvement of autism spectrum disorder: focus on gut microbiota. Expert Rev Gastroenterol Hepatol. 2021;599–622. https://doi.org/10.1080/17474124.2021.1869938

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(6):1600–18.e17. https://doi.org/10.1016/j.cell.2019.05.004

Sivamaruthi BS, Suganthy N, Kesika P, Chaiyasut C. The role of microbiome, dietary supplements, and probiotics in autism spectrum disorder. Int J Environ Res Public Health. 2020;17(8):2647. https://doi.org/10.3390/ijerph17082647

Srikantha P, Mohajeri MH. The possible role of the microbiota-gut-brain-axis in autism spectrum disorder. Int J Mol Sci. 2019;20(9):2115. https://doi.org/10.3390/ijms20092115

Sun H, You Z, Jia L, Wang F. Autism spectrum disorder is associated with gut microbiota disorder in children. BMC Pediatr. 2019;(1)516. https://doi.org/10.1186/s12887-019-1896-6

Taniya MA, Chung HJ, Mamun AA, Alam S, Aziz MA, Emon NU, et al. Role of gut microbiome in autism spectrum disorder and its therapeutic regulation. Front Cell Infect Microbiol. 2022;12:915701. https://doi.org/10.3389/fcimb.2022.915701

Tu T, Zhao C. Treating autism spectrum disorder by intervening with gut microbiota. J Med Microbiol. 2021;70(12). https://doi.org/10.1099/jmm.0.001469

Valenzuela-Zamora AF, Ramírez-Valenzuela DG, Ramos-Jiménez A. Food selectivity and its implications associated with gastrointestinal disorders in children with autism spectrum disorders. Nutrients. 2022;14(13):2660. https://doi.org/10.3390/nu14132660

Vellingiri B, Aishwarya SY, Jancy SB, Abhishek GS, Babu HWS, Vijayakumar P, et al. An anxious relationship between autism spectrum disorder and gut microbiota: a tangled chemistry? J Clin Neurosci. 2022;169–89. https://doi.org/10.1016/j.jocn.2022.03.003

Wong GC, Montgomery JM, Taylor MW, Grabrucker AM. The gut-microbiota-brain axis in autism spectrum disorder. Exon Publ. 2021. https://doi.org/10.36255/exonpublications.autismspectrumdisorders.2021.gutmicrobiota

Wong OWH, Lam AMW, Or BPN, Mo FYM, Shea CKS, Lai KYC, et al. Disentangling the relationship of gut microbiota, functional gastrointestinal disorders and autism: a case-control study on prepubertal Chinese boys. Sci Rep. 2022;12:10659. https://doi.org/10.1038/s41598-022-14785-8

Xu M, Xu X, Li J, Li F. Association between gut microbiota and autism spectrum disorder: a systematic review and meta-analysis. Front Psychiatry. 2019;10:473. https://doi.org/10.3389/fpsyt.2019.00473

Yap CX, Handers AK, Alvares GA, Wood DLA, Krause L, Tyson GW, et al. Autism-related dietary preferences mediate autism-gut microbiome associations. Cell. 2021;184(24):5916-31. https://doi.org/10.1016/j.cell.2021.10.015