Alteraciones gastrointestinales en el autismo: una revisión

Flower de MJ Caycho-Salazar, Deissy Herrera-Covarrubias, María Rebeca Toledo-Cárdenas, María Elena Hernández-Aguilar, Genaro A. Coria-Ávila, Luis I. García, Darwin Gutiérrez-Guevara, Bernardo Flores-Prieto, Jorge Manzo Denes

Resumen


El autismo, actualmente denominado trastorno del espectro autista (TEA), se define como una alteración del neurodesarrollo caracterizado por dificultades a nivel conductual y socio-comunicativo. Se ha reportado que el TEA presenta una comorbilidad con alteraciones gastrointestinales (GI). Los objetivos de esta revisión fueron tres y estuvieron enfocados en explorar la evidencia de personas con TEA que hayan reportado presentar alteraciones GI, analizar la relación entre el TEA y la composición de la microbiota intestinal, así como la relación entre las intervenciones enfocadas a modificar síntomas GI y algunos comportamientos asociados al TEA. Para ello, fueron analizados artículos de los últimos cinco años. La revisión fue realizada siguiendo las pautas PRISMA-P de investigaciones en humanos encontradas en PubMed y ScienceDirect, incluyendo finalmente 13 artículos: 11 estudios empíricos y 2 de tipo metaanálisis. Los resultados arrojaron que las personas con TEA presentan alteraciones GI más frecuentes como estreñimiento y diarrea, evidenciando así una relación entre alteraciones GI y TEA. Sobre la relación del TEA y la composición de la microbiota intestinal se reportó una heterogeneidad en la presencia de grupos de bacterias en cohortes con autismo y que presentan una composición disbiótica de la microbiota intestinal. Finalmente, se encontraron intervenciones enfocadas en mejorar síntomas GI y comportamientos disruptivos, como el trasplante fecal y la administración de dietas con probióticos.

Abstract

Autism, currently called autism spectrum disorder (ASD), is defined as a neurodevelopmental disorder characterized by behavioral and socio-communicative difficulties. It has been reported that ASD presents comorbidity with gastrointestinal (GI) disorders. The objectives of this review were three and focused on exploring the evidence of people with ASD who have reported presenting GI alterations, analyzing the relationship between ASD and the composition of the intestinal microbiota, as well as the relationship between interventions focused on modifying symptoms. GI and some behaviors associated with ASD. For this, articles from the last five years were analyzed. The review was carried out following the PRISMA-P guidelines for human research found in PubMed and ScienceDirect, finally including 13 articles: 11 empirical studies and 2 meta-analysis types. The results showed that people with ASD present more frequent GI disorders such as constipation and diarrhea, thus evidencing a relationship between GI disorders and ASD. Regarding the relationship between ASD and the composition of the intestinal microbiota, heterogeneity was reported in the presence of groups of bacteria in cohorts with autism that present a dysbiotic composition of the intestinal microbiota. Finally, interventions focused on improving GI symptoms and disruptive behaviors were found, such as fecal transplantation and the administration of diets with probiotics.

Keywords: Autism; gastrointestinal alterations; intestinal microbiota; fecal transplantation; probiotics.


Palabras clave


Autismo, alteraciones gastrointestinales, microbiota intestinal, trasplante fecal, probióticos.

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Referencias


Manual Diagnóstico y Estadístico de los Trastornos Mentales DSM-5-TR. (2014). Masson.

Goldani, A. A. S., Downs, S. R., Widjaja, F., Lawton, B., & Hendren, R. L. (2014). Biomarkers in Autism. Frontiers in psychiatry, 5,100. https://doi.org/10.3389/fpsyt.2014.00100

Chaste, P., & Leboyer, M. (2012). Autism risk factors: genes, environment, and gene-environment interactions. Dialogues in clinical neuroscience, 14(3), 281–292. https://doi.org/10.31887/DCNS.2012.14.3/pchaste

Bjørklund, G., Meguid, N. A., El-Bana, M. A., Tinkov, A. A., Saad, K., Dadar, M., Hemimi, M., Skalny, A. V., Hosnedlová, B., Kizek, R., Osredkar, J., Urbina, M. A., Fabjan, T., El-Houfey, A. A., Kałużna-Czaplińska, J., Gątarek, P., & Chirumbolo, S. (2020). Oxidative stress in autism spectrum disorder. Molecular Neurobiology, 57(5), 2314–2332. https://doi.org/10.1007/s12035-019-01742-2

Díaz-Anzaldúa, A., & Díaz-Martínez, A. (2013). Contribución genética, ambiental y epigenética en la susceptibilidad a los trastornos del espectro autista [Genetic, environmental, and epigenetic contribution to the susceptibility to autism spectrum disorders]. Revista de neurologia, 57(12), 556–568.

Bhat, S., Acharya, U. R., Adeli, H., Bairy, G. M., & Adeli, A. (2014). Autism: cause factors, early diagnosis and therapies. Reviews in the neurosciences, 25(6). https://doi.org/10.1515/revneuro-2014-0056

Matsuzaki, H., Iwata, K., Manabe, T., & Mori, N. (2012). Triggers for autism: Genetic and environmental factors. Journal of Central Nervous System Disease, 4, JCNSD.S9058. https://doi.org/10.4137/jcnsd.s9058

Christensen, J., Grønborg, T. K., Sørensen, M. J., Schendel, D., Parner, E. T., Pedersen, L. H., & Vestergaard, M. (2013). Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA: The Journal of the American Medical Association, 309(16), 1696. https://doi.org/10.1001/jama.2013.2270

McElhanon, B. O., McCracken, C., Karpen, S., & Sharp, W. G. (2014). Gastrointestinal symptoms in autism spectrum disorder: A meta-analysis. Pediatrics, 133(5), 872–883. https://doi.org/10.1542/peds.2013-3995

Penzol, M. J., Salazar de Pablo, G., Llorente, C., Moreno, C., Hernández, P., Dorado, M. L., & Parellada, M. (2019). Functional Gastrointestinal Disease in Autism Spectrum Disorder: A Retrospective Descriptive Study in a Clinical Sample. Frontiers in psychiatry, 10, 179. https://doi.org/10.3389/fpsyt.2019.00179

Bernier, R., Golzio, C., Xiong, B., Stessman, H. A., Coe, B. P., Penn, O., Witherspoon, K., Gerdts, J., Baker, C., Vulto-van Silfhout, A. T., Schuurs-Hoeijmakers, J. H., Fichera, M., Bosco, P., Buono, S., Alberti, A., Failla, P., Peeters, H., Steyaert, J., Vissers, L. E. L. M., … Eichler, E. E. (2014). Disruptive CHD8 mutations define a subtype of autism early in development. Cell, 158(2), 263–276. https://doi.org/10.1016/j.cell.2014.06.017

Chaidez, V., Hansen, R. L., & Hertz-Picciotto, I. (2014). Gastrointestinal problems in children with autism, developmental delays or typical development. Journal of autism and developmental disorders, 44(5), 1117–1127. https://doi.org/10.1007/s10803-013-1973-x

Holingue, C., Newill, C., Lee, L.-C., Pasricha, P. J., & Daniele Fallin, M. (2018). Gastrointestinal symptoms in autism spectrum disorder: A review of the literature on ascertainment and prevalence: Gastrointestinal Symptoms in Autism Spectrum Disorder. Autism Research: Official Journal of the International Society for Autism Research, 11(1), 24–36. https://doi.org/10.1002/aur.1854

Johnson, A. C., Louwies, T., Yuan, T., Orock, A., & Greenwood-Van Meerveld, B. (2020). Gut and brain interactions. En Clinical and Basic Neurogastroenterology and Motility. Elsevier.

Mohajeri, M. H., La Fata, G., Steinert, R. E., & Weber, P. (2018). Relationship between the gut microbiome and brain function. Nutrition Reviews, 76(7), 481–496. https://doi.org/10.1093/nutrit/nuy009

Góralczyk-Bińkowska, A., Szmajda-Krygier, D., & Kozłowska, E. (2022). The Microbiota-Gut-Brain Axis in Psychiatric Disorders. International journal of molecular sciences, 23(19), 11245. https://doi.org/10.3390/ijms231911245

Doroszkiewicz, J., Groblewska, M., & Mroczko, B. (2021). The Role of Gut Microbiota and Gut-Brain Interplay in Selected Diseases of the Central Nervous System. International journal of molecular sciences, 22(18), 10028. https://doi.org/10.3390/ijms221810028

De Angelis, M., Francavilla, R., Piccolo, M., De Giacomo, A., & Gobbetti, M. (2015). Autism spectrum disorders and intestinal microbiota. Gut microbes, 6(3), 207–213. https://doi.org/10.1080/19490976.2015.1035855

Socała, K., Doboszewska, U., Szopa, A., Serefko, A., Włodarczyk, M., Zielińska, A., Poleszak, E., Fichna, J., & Wlaź, P. (2021). The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders. Pharmacological Research: The Official Journal of the Italian Pharmacological Society, 172(105840), 105840. https://doi.org/10.1016/j.phrs.2021.105840

Matta, S. M., Hill-Yardin, E. L., & Crack, P. J. (2019). The influence of neuroinflammation in Autism Spectrum Disorder. Brain, Behavior, and Immunity, 79, 75–90. https://doi.org/10.1016/j.bbi.2019.04.037

Xu, M., Xu, X., Li, J., & Li, F. (2019). Association between gut Microbiota and autism spectrum disorder: A systematic review and meta-analysis. Frontiers in psychiatry, 10. https://doi.org/10.3389/fpsyt.2019.00473

Li, Q., Han, Y., Dy, A. B. C., & Hagerman, R. J. (2017). The gut Microbiota and autism spectrum disorders. Frontiers in cellular neuroscience, 11. https://doi.org/10.3389/fncel.2017.00120

Luna, R. A., Oezguen, N., Balderas, M., Venkatachalam, A., Runge, J. K., Versalovic, J., Veenstra-VanderWeele, J., Anderson, G. M., Savidge, T., & Williams, K. C. (2017). Distinct microbiome-neuroimmune signatures correlate with functional abdominal pain in children with autism spectrum disorder. Cellular and Molecular Gastroenterology and Hepatology, 3(2), 218–230. https://doi.org/10.1016/j.jcmgh.2016.11.008

Quigley, E. M. M. (2016). Leaky gut – concept or clinical entity? Current Opinion in Gastroenterology, 32(2), 74–79. https://doi.org/10.1097/mog.0000000000000243

Garcia-Gutierrez, E., Narbad, A., & Rodríguez, J. M. (2020). Autism spectrum disorder associated with gut Microbiota at immune, metabolomic, and neuroactive level. Frontiers in neuroscience, 14. https://doi.org/10.3389/fnins.2020.578666

Sandler, R. H., Finegold, S. M., Bolte, E. R., Buchanan, C. P., Maxwell, A. P., Väisänen, M.-L., Nelson, M. N., & Wexler, H. M. (2000). Short-term benefit from oral vancomycin treatment of regressive-onset autism. Journal of Child Neurology, 15(7), 429–435. https://doi.org/10.1177/088307380001500701

Kang, D. W., Adams, J. B., Gregory, A. C., Borody, T., Chittick, L., Fasano, A., Khoruts, A., Geis, E., Maldonado, J., McDonough-Means, S., Pollard, E. L., Roux, S., Sadowsky, M. J., Lipson, K. S., Sullivan, M. B., Caporaso, J. G., & Krajmalnik-Brown, R. (2017). Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome, 5(1), 10. https://doi.org/10.1186/s40168-016-0225-7

Leader, G., Barrett, A., Ferrari, C., Casburn, M., Maher, L., Naughton, K., Arndt, S., & Mannion, A. (2021). Quality of life, gastrointestinal symptoms, sleep problems, social support, and social functioning in adults with autism spectrum disorder. Research in Developmental Disabilities, 112(103915), 103915. https://doi.org/10.1016/j.ridd.2021.103915

Leader, G., Browne, H., Whelan, S., Cummins, H., & Mannion, A. (2022). Affective problems, gastrointestinal symptoms, sleep problems, and challenging behaviour in children and adolescents with autism spectrum disorder. Research in Autism Spectrum Disorders, 92(101915), 101915. https://doi.org/10.1016/j.rasd.2022.101915

Chen, Y.-C., Lin, H.-Y., Chien, Y., Tung, Y.-H., Ni, Y.-H., & Gau, S. S.-F. (2022). Altered gut microbiota correlates with behavioral problems but not gastrointestinal symptoms in individuals with autism. Brain, Behavior, and Immunity, 106, 161–178. https://doi.org/10.1016/j.bbi.2022.08.015

Şengüzel, S., Cebeci, A. N., Ekici, B., Gönen, İ., & Tatlı, B. (2021). Impact of eating habits and nutritional status on children with autism spectrum disorder. Journal of Taibah University Medical Sciences, 16(3), 413–421. https://doi.org/10.1016/j.jtumed.2020.11.010

Ye, F., Gao, X., Wang, Z., Cao, S., Liang, G., He, D., Lv, Z., Wang, L., Xu, P., & Zhang, Q. (2021). Comparison of gut microbiota in autism spectrum disorders and neurotypical boys in China: A case-control study. Synthetic and Systems Biotechnology, 6(2), 120–126. https://doi.org/10.1016/j.synbio.2021.03.003

Ding, X., Xu, Y., Zhang, X., Zhang, L., Duan, G., Song, C., Li, Z., Yang, Y., Wang, Y., Wang, X., & Zhu, C. (2020). Gut microbiota changes in patients with autism spectrum disorders. Journal of Psychiatric Research, 129, 149–159. https://doi.org/10.1016/j.jpsychires.2020.06.032

Li, N., Yang, J., Zhang, J., Liang, C., Wang, Y., Chen, B., Zhao, C., Wang, J., Zhang, G., Zhao, D., Liu, Y., Zhang, L., Yang, J., Li, G., Gai, Z., Zhang, L., & Zhao, G. (2019). Correlation of gut microbiome between ASD children and mothers and potential biomarkers for risk assessment. Genomics, Proteomics & Bioinformatics, 17(1), 26–38. https://doi.org/10.1016/j.gpb.2019.01.002

Kang, D.-W., Adams, J. B., Coleman, D. M., Pollard, E. L., Maldonado, J., McDonough-Means, S., Caporaso, J. G., & Krajmalnik-Brown, R. (2019). Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Scientific Reports, 9(1), 5821. https://doi.org/10.1038/s41598-019-42183-0

Arnold, L. E., Luna, R. A., Williams, K., Chan, J., Parker, R. A., Wu, Q., Hollway, J. A., Jeffs, A., Lu, F., Coury, D. L., Hayes, C., & Savidge, T. (2019). Probiotics for gastrointestinal symptoms and quality of life in autism: A placebo-controlled pilot trial. Journal of Child and Adolescent Psychopharmacology, 29(9), 659–669. https://doi.org/10.1089/cap.2018.0156

Sanctuary, M. R., Kain, J. N., Chen, S. Y., Kalanetra, K., Lemay, D. G., Rose, D. R., Yang, H. T., Tancredi, D. J., German, J. B., Slupsky, C. M., Ashwood, P., Mills, D. A., Smilowitz, J. T., & Angkustsiri, K. (2019). Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms. PloS One, 14(1), e0210064. https://doi.org/10.1371/journal.pone.0210064

Nogay, N. H., Walton, J., Roberts, K. M., Nahikian-Nelms, M., & Witwer, A. N. (2021). The effect of the low FODMAP diet on gastrointestinal symptoms, behavioral problems and nutrient intake in children with autism spectrum disorder: A randomized controlled pilot trial. Journal of Autism and Developmental Disorders, 51(8), 2800–2811. https://doi.org/10.1007/s10803-020-04717-8

Abraham, D. A., Undela, K., Narasimhan, U., & Rajanandh, M. G. (2021). Effect of L-Carnosine in children with autism spectrum disorders: a systematic review and meta-analysis of randomised controlled trials. Amino Acids, 53(4), 575–585. https://doi.org/10.1007/s00726-021-02960-6

Song, W., Zhang, M., Teng, L., Wang, Y., & Zhu, L. (2022). Prebiotics and probiotics for autism spectrum disorder: a systematic review and meta-analysis of controlled clinical trials. Journal of Medical Microbiology, 71(4). https://doi.org/10.1099/jmm.0.001510

Forootan, M., Bagheri, N., & Darvishi, M. (2018). Chronic constipation: A review of literature. Medicine, 97(20), e10631. https://doi.org/10.1097/md.0000000000010631

Sharma, A., & Rao, S. (2016). Constipation: Pathophysiology and current therapeutic approaches. En Gastrointestinal Pharmacology (pp. 59–74). Springer International Publishing. https://doi.org/10.1007/164_2016_111

Cermak, S. A., Curtin, C., & Bandini, L. G. (2010). Food selectivity and sensory sensitivity in children with autism spectrum disorders. Journal of the American Dietetic Association, 110(2), 238–246. https://doi.org/10.1016/j.jada.2009.10.032

Esposito, M., Mirizzi, P., Fadda, R., Pirollo, C., Ricciardi, O., Mazza, M., & Valenti, M. (2023). Food selectivity in children with autism: Guidelines for assessment and clinical interventions. International Journal of Environmental Research and Public Health, 20(6), 5092. https://doi.org/10.3390/ijerph20065092

Viviers, M., Jongh, M., Dickonson, L., Malan, R., & Pike, T. (2020). Parent-reported feeding and swallowing difficulties of children with Autism Spectrum Disorders (aged 3 to 5 years) compared to typically developing peers: a South African study. African health sciences, 20(1), 524–532. https://doi.org/10.4314/ahs.v20i1.59

Luo, J., Li, Y., Xie, J., Gao, L., Liu, L., Ou, S., Chen, L., & Peng, X. (2018). The primary biological network of Bifidobacterium in the gut. FEMS Microbiology Letters, 365(8). https://doi.org/10.1093/femsle/fny057

Donaldson, G. P., Lee, S. M., & Mazmanian, S. K. (2016). Gut biogeography of the bacterial microbiota. Nature Reviews. Microbiology, 14(1), 20–32. https://doi.org/10.1038/nrmicro3552

Kang, D.-W., Park, J. G., Ilhan, Z. E., Wallstrom, G., Labaer, J., Adams, J. B., & Krajmalnik-Brown, R. (2013). Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PloS One, 8(7), e68322. https://doi.org/10.1371/journal.pone.0068322

Tomova, A., Husarova, V., Lakatosova, S., Bakos, J., Vlkova, B., Babinska, K., & Ostatnikova, D. (2015). Gastrointestinal microbiota in children with autism in Slovakia. Physiology & behavior, 138, 179–187. https://doi.org/10.1016/j.physbeh.2014.10.033

De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D. I., Cristofori, F., Guerzoni, M. E., 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

Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G., Gasbarrini, A., & Mele, M. (2019). What is the healthy gut Microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms, 7(1), 14. https://doi.org/10.3390/microorganisms7010014

Magne, F., Gotteland, M., Gauthier, L., Zazueta, A., Pesoa, S., Navarrete, P., & Balamurugan, R. (2020). The Firmicutes/Bacteroidetes ratio: A relevant marker of gut dysbiosis in obese patients? Nutrients, 12(5), 1474. https://doi.org/10.3390/nu12051474

Qin, J., MetaHIT Consortium, Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., Yamada, T., Mende, D. R., Li, J., Xu, J., Li, S., Li, D., Cao, J., Wang, B., Liang, H., … Wang, J. (2010). A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 464(7285), 59–65. https://doi.org/10.1038/nature08821

Parracho, H. M., Bingham, M. O., Gibson, G. R., & McCartney, A. L. (2005). Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. Journal of Medical Microbiology, 54(Pt 10), 987–991. https://doi.org/10.1099/jmm.0.46101-0

Stefano, G. B., Pilonis, N., Ptacek, R., Raboch, J., Vnukova, M., & Kream, R. M. (2018). Gut, microbiome, and brain regulatory axis: Relevance to neurodegenerative and psychiatric disorders. Cellular and Molecular Neurobiology, 38(6), 1197–1206. https://doi.org/10.1007/s10571-018-0589-2

Dicks, L. M. T. (2022). Gut bacteria and neurotransmitters. Microorganisms, 10(9), 1838. https://doi.org/10.3390/microorganisms10091838

Barrett, E., Ross, R. P., O’Toole, P. W., Fitzgerald, G. F., & Stanton, C. (2012). γ-Aminobutyric acid production by culturable bacteria from the human intestine. Journal of Applied Microbiology, 113(2), 411–417. https://doi.org/10.1111/j.1365-2672.2012.05344.x

Celebi Sözener, Z., Cevhertas, L., Nadeau, K., Akdis, M., & Akdis, C. A. (2020). Environmental factors in epithelial barrier dysfunction. The Journal of allergy and clinical immunology, 145(6), 1517–1528. https://doi.org/10.1016/j.jaci.2020.04.024

Li, X., Li, R., You, N., Zhao, X., Li, J., & Jiang, W. (2022). Butyric Acid Ameliorates Myocardial Fibrosis by Regulating M1/M2 Polarization of Macrophages and Promoting Recovery of Mitochondrial Function. Frontiers in nutrition, 9, 875473. https://doi.org/10.3389/fnut.2022.875473

Manrique Vergara, D., & González Sánchez, M. E. (2017). Ácidos grasos de cadena corta (ácido butírico) y patologías intestinales [Short chain fatty acids (butyric acid) and intestinal diseases]. Nutricion hospitalaria, 34(Suppl 4), 58–61. https://doi.org/10.20960/nh.1573

Health Canada (2015). Guidance Document: Fecal Microbiota Therapy Used in the Treatment of Clostridium difficile Infections. Health Canada.

Draft Guidance for Industry: Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies. (2014). US Food and Drug Administration.

Gupta, S., Allen-Vercoe, E., & Petrof, E. O. (2016). Fecal microbiota transplantation: in perspective. Therapeutic Advances in Gastroenterology, 9(2), 229–239. https://doi.org/10.1177/1756283X15607414

Donohoe, D. R., Garge, N., Zhang, X., Sun, W., O’Connell, T. M., Bunger, M. K., & Bultman, S. J. (2011). The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell metabolism, 13(5), 517–526. https://doi.org/10.1016/j.cmet.2011.02.018

Hill, P., Muir, J. G., & Gibson, P. R. (2017). Controversies and recent developments of the low-FODMAP diet. Gastroenterology & Hepatology, 13(1), 36–45.




DOI: https://doi.org/10.25009/eb.v14i36.2626

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