International Journal for Autism Challenges & Solution

Browse Journals

Articles

Vol. 2 No. 2 (2025): International Journal for Autism Challenges & Solution

A Potential Link between Gut Leakiness and Sex Differences in Autism Spectrum Disorder (ASD)

  • Hanan Farouk Aly
Submitted
November 24, 2025
Published
2025-12-27

Abstract

Background: Autism is categorized as autism spectrum disorder (ASD), characterized by recurrent behaviors and difficulties with social communication that can affect different body systems and are linked to gut microbiota dysbiosis (GM). The importance of altered GM in autistic people, the ways in which these changes could result in leaky gut, and the possible connection between sex differences and this problem are all highlighted in this paper. Main body: Research indicates that increased intestinal barrier permeability may play a significant role in the pathological changes seen in autism; it makes it easier for gut-derived endotoxins to enter the brain, where they activate the TLR4–MyD88–NF-κB signaling cascade and create an inflammatory environment. There have been differences found in the amounts of various bacterial metabolites, such as beta cresol, short-chain fatty acids, lipopolysaccharides, and bacterial toxins, in the blood and urine of children with autism. Additionally, the importance of particular proteins like zonulin, lysozyme, and calprotectin as biomarkers that can detect the leaky gut in ASD at an early stage has been shown. Bacterial metabolite leakage in these patients may be explained by disruption of the gut blood–brain barrier. As a result, a number of microbiota manipulation techniques have been developed to balance out sex differences. Male ASD sufferers are four times as likely as female ASD sufferers. Additionally, in both human and animal models of this illness, such as the maternal immune activation (MIA) mice model, the composition of GM is dependent on sex. However, very few studies have taken sex's biological impact into account when assessing how GM affects symptoms of ASD. MIA increases pro-inflammatory cytokines and chemokines in the mother, such as interleukin, IL-6, and IL-17α, which interfere with the development of the fetal brain. According to recent studies, MIA causes GM dysbiosis. This is significant because the GM, which lives in the gastrointestinal (GI) tract, contributes to the development of the immunological, neurological, and metabolic systems through the microbiota-gut-brain axis, resulting in characteristics that resemble ASD in the MIA model.Research exploring the impact of GM on ASD etiology primarily focuses on men, ignoring the recipient's and donor's sex/gender, even though biological distinctions linked to sex, GM, and leaky gut have been discovered to be correlated with each other. In the MIA model, sex-mediated gut-immune interactions were found in the few research that take into account the biological impact of sex.The limited studies that consider the biological effect of sex revealed sex-mediated gut-immune interactions in the MIA model. Conclusion: Given that many people with autism have gastrointestinal problems, this review emphasizes the possible link between ASD and GM. The involvement of altered GM in autistic people, how these changes result in leaky gut, and the possible connection between leaky gut and sex differences are all covered. Furthermore, this study offers a number of promising therapeutic therapies, including as intestinal proteins, some probiotics, and chemicals derived from bacteria, as novel approaches to reestablish a healthy GM.

References

  1. Lord, C., Elsabbagh, M., Baird, G., and Veenstra-Vanderweele, J. (2018). Autism spectrum disorder. Lancet (London, England), 392(10146), 508–520. https://doi.org/10.1016/S0140-6736 (18)31129-2. DOI: https://doi.org/10.1016/S0140-6736(18)31129-2
  2. Zeidan, J., Fombonne, E., Scorah, J., Ibrahim, A., Durkin, M. S., Saxena, S., Yusuf, A., Shih, A., & Elsabbagh, M. (2022). Global prevalence of autism: A systematic review update. Autism research: Official Journal of the International Society for Autism Research, 15(5), 778–790. https://doi.org/10.1002/aur.2696 DOI: https://doi.org/10.1002/aur.2696
  3. Rogge, N., & Janssen, J. (2019). The economic costs of autism spectrum disorder: A literature review. Journal of Autism and Developmental Disorders, 49(7), 2873–2900. https://doi.org/10.1007/s10803-019-04014-z DOI: https://doi.org/10.1007/s10803-019-04014-z
  4. Drapeau, E., Riad, M., Kajiwara, Y., & Buxbaum, J. D. (2018). Behavioral phenotyping of an improved mouse model of phelan-mcdermid syndrome with a complete deletion of the Shank3 gene. eNeuro, 5(3), ENEURO.0046-18.2018. https://doi.org/10.1523/ENEURO.0046-18.2018 DOI: https://doi.org/10.1523/ENEURO.0046-18.2018
  5. Loomes, R., Hull, L., & Mandy, W. P. L. (2017). What is the male-to-female ratio in autism spectrum disorder? A systematic review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 56(6), 466–474. https://doi.org/10.1016/j.jaac.2017.03.013 DOI: https://doi.org/10.1016/j.jaac.2017.03.013
  6. Werling, D. M., & Geschwind, D. H. (2013). Sex differences in autism spectrum disorders. Current Opinion in Neurology,26(2), 146–153. https://doi.org/10.1097/WCO.0b013e32835ee548 DOI: https://doi.org/10.1097/WCO.0b013e32835ee548
  7. Werling D. M. (2016). The role of sex-differential biology in risk for autism spectrum disorder. Biology of Sex Differences, 7, 58. https://doi.org/10.1186/s13293-016-0112-8 DOI: https://doi.org/10.1186/s13293-016-0112-8
  8. Abujame, T.S. , Al-Otaibi, N.M., Abuaish, S. , AlHarbi, R.H. , Assas, M.B., Alzahrani, S.A., Alotaibi, S.M., El-Ansary, A. and Aabed, K. (2022).Different Alterations in GM between Bifidobacterium longum and fecal microbiota transplantation treatments in propionic acid rat model of autism. nutrients, 14, 608. https://doi.org/10.3390/nu14030608 DOI: https://doi.org/10.3390/nu14030608
  9. Kang, D. W. et al. (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 DOI: https://doi.org/10.1186/s40168-016-0225-7
  10. Kang, D. W. et al. (2019).Long-term benefit of microbiota transfer therapy on autism symptoms and GM. Sci. Rep. 9, 5821. https://doi.org/10.1038/s41598-019-42183-0 DOI: https://doi.org/10.1038/s41598-019-42183-0
  11. Wong, O. W. H. et al. (2022).Disentangling the relationship of GM, functional gastrointestinal disorders and autism: A case-control study on prepubertal Chinese boys. Sci. Rep. 12, 10659. https://doi.org/10.1038/s41598-022-14785-8 DOI: https://doi.org/10.1038/s41598-022-14785-8
  12. Mehra, A. et al. (2022).GM and autism spectrum disorder: From pathogenesis to potential therapeutic perspectives. J. Tradit. Complement. Med. 13(2), 135–149. DOI: https://doi.org/10.1016/j.jtcme.2022.03.001
  13. Patel, S., Dale, R. C., Rose, D., Heath, B., Nordahl, C. W., Rogers, S., Guastella, A. J., & Ashwood, P. (2020). Maternal immune conditions are increased in males with autism spectrum disorders and are associated with behavioural and emotional but not cognitive comorbidity. Translational Psychiatry, 10(1), 286. https://doi.org/10.1038/s41398-020-00976-14. DOI: https://doi.org/10.1038/s41398-020-00976-2
  14. Smith, S. E., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007). Maternal immune activation alters fetal brain development through interleukin-6. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 27(40), 10695– 10702. https://doi.org/10.1523/JNEUROSCI.2178-07.2007 DOI: https://doi.org/10.1523/JNEUROSCI.2178-07.2007
  15. Haida, O., Al Sagheer, T., Balbous, A., Francheteau, M., Matas, E., Soria, F., Fernagut, P. O., & Jaber, M. (2019). Sex-dependent behavioral deficits and neuropathology in a maternal immune activation model of autism. Translational Psychiatry,9(1), 1–12. https://doi.org/10.1038/s41398-019-0457-y DOI: https://doi.org/10.1038/s41398-019-0457-y
  16. Hsiao, E. Y., McBride, S. W., Hsien, S., Sharon, G., Hyde, E. R., McCue, T., Codelli, J. A., Chow, J., Reisman, S. E., Petrosino, J. F., Patterson, P. H., & Mazmanian, S. K. (2013). Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell,155(7), 1451–1463. DOI: https://doi.org/10.1016/j.cell.2013.11.024
  17. Juckel, G., Manitz, M. P., Freund, N., & Gatermann, S. (2021). Impact of Poly I:C induced maternal immune activation on offspring’s gut microbiome diversity - Implications for schizophrenia. Progress in Neuro-psychopharmacology & Biological Psychiatry, 110, 110306. https://doi.org/10.1016/j.pnpbp.2021.110306. DOI: https://doi.org/10.1016/j.pnpbp.2021.110306
  18. Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of Gastroenterology, 28(2), 203–209.
  19. Sandoval-Motta, S., Aldana, M., Martínez-Romero, E., & Frank, A. (2017). The human microbiome and the missing heritability problem. Frontiers in Genetics, 8, 80. https://doi.org/10.3389/fgene.2017.00080 DOI: https://doi.org/10.3389/fgene.2017.00080
  20. Sharon, G., Cruz, N. J., Kang, D. W., Gandal, M. J., Wang, B., Kim, Y. M., & Mazmanian, S. K. (2019). Human GM from autism spectrum disorder promote behavioral symptoms in mice. Cell, 177(6), 1600-1618.e17. https://doi.org/10.1016/j.cell.2019.05.004 DOI: https://doi.org/10.1016/j.cell.2019.05.004
  21. Xiao, L., Yan, J., Yang, T., Zhu, J., Li, T., Wei, H., & Chen, J. (2021). Fecal microbiome transplantation from children with autism spectrum disorder modulates tryptophan and serotonergic synapse metabolism and induces altered behaviors in germ-free mice. Msystems,6(2), e01343-20. https://doi.org/10.1128/mSystems.01343-20 DOI: https://doi.org/10.1128/msystems.01343-20
  22. Kim, Y. S., Unno, T., Kim, B. Y., & Park, M. S. (2020). Sex differences in GM. The World Journal of Men’s Health, 38(1), 48–60. https://doi.org/10.5534/wjmh.190009 DOI: https://doi.org/10.5534/wjmh.190009
  23. Desbonnet, L., Clarke, G., Shanahan, F., Dinan, T. G., & Cryan, J. F. (2014). Microbiota is essential for social development in the mouse. Molecular psychiatry, 19(2), 146–148. https://doi.org/10.1038/mp.2013.65 DOI: https://doi.org/10.1038/mp.2013.65
  24. Salia, S., Martin, Y., Burke, F. F., Myles, L. A., Jackman, L., Halievski, K., Bambico, F. R., & Swift-Gallant, A. (2023). Antibiotic-induced socio-sexual behavioral deficits are reversed via cecal microbiota transplantation but not androgen treatment. Brain, Behavior, & Immunity - Health, 30, 100637. https://doi.org/10.1016/j.bbih.2023.100637 DOI: https://doi.org/10.1016/j.bbih.2023.100637
  25. Thion, M. S., Low, D., Silvin, A., Chen, J., Grisel, P., Schulte-Schrepping, J., Blecher, R., Ulas, T., Squarzoni, P., Hoeffel, G., Coulpier, F., Siopi, E., David, F. S., Scholz, C., Shihui, F., Lum, J., Amoyo, A. A., Larbi, A., Poidinger, M., Buttgereit, A., … Garel, S. (2018). Microbiome influences prenatal and adult microglia in a sex-specific manner. Cell, 172(3), 500–516.e16. https://doi.org/10.1016/j.cell.2017.11.042 DOI: https://doi.org/10.1016/j.cell.2017.11.042
  26. O'Grady, K. and Grabrucker, A.M.(2025).Metal Dyshomeostasis as a Driver of Gut Pathology in Autism Spectrum Disorders.Journal of Neurochemistry,169:e70041 1 of 20 https://doi.org/10.1111/jnc.70041 DOI: https://doi.org/10.1111/jnc.70041
  27. American Psychiatric Association. (2022). “Diagnostic and Statistical Manual of Mental Disorders.” In Text Rev. (DSM-5-TR), 5th ed. Arlington: American Psychiatric Association. DOI: https://doi.org/10.1176/appi.books.9780890425787
  28. Hull, L., Petrides,K. V. and Mandy,W.(2020). “The Female Autism Phenotype and Camouflaging: A Narrative Review.” Review Journal of Autism and Developmental Disorders, 7 (4), 306–17. DOI: https://doi.org/10.1007/s40489-020-00197-9
  29. Mao H, Cheng L, Zhang Y and Zhang F.(2024). A review article Gender Differences in Autism Spectrum Disorder: A systematic review of diagnosis, intervention, and outcomes. Gend. Sustain. Glob. South. 2024; 1(1), 92–136. DOI: https://doi.org/10.1515/gsgs-2024-0007
  30. Hodges, H., Fealko, C., Soares, N.(2020). Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation. Transl Pediatr. 9(Suppl 1),S55-S65 | http://dx.doi.org/10.21037/tp.2019.09.09. DOI: https://doi.org/10.21037/tp.2019.09.09
  31. Shen, M.D., Kim, S.H., McKinstry, R.C., et al. (2017).Increased extra-axial cerebrospinal fluid in high-risk infants who later develop autism. Biol Psychiatry, 82,186-93. DOI: https://doi.org/10.1016/j.biopsych.2017.02.1095
  32. Kim, H., Keifer, C., Rodriguez-Seijas, C., et al. (2019).Quantifying the optimal structure of the autism phenotype: a comprehensive comparison of dimensional, categorical, and hybrid models. J Am Acad Child Adolesc Psychiatry, 58,876-86.e2. DOI: https://doi.org/10.1016/j.jaac.2018.09.431
  33. Sabatini, G, Boccadoro, I., Prete, R., Battista, N. and Corsetti, A. (2025).Autism Spectrum Disorder: From Experimental Models to Probiotic Application with a Special Focus on Lactiplantibacillus planetarium. Nutrients, 17, 2470 https://doi.org/10.3390/nu17152470 DOI: https://doi.org/10.3390/nu17152470
  34. Wu, T., Wang, H., Lu, W., Zhai, Q., Zhang, Q., Yuan, W., Gu, Z., Zhao, J., Zhang, H., & Chen, W. (2020). Potential of gut microbiome for detection of autism spectrum disorder.Microbial Pathogenesis, 149, 104568. DOI: https://doi.org/10.1016/j.micpath.2020.104568
  35. Golubeva, A. V., Joyce, S. A., Moloney, G., Burokas, A., Sherwin, E., Arboleya, S., Flynn, I., Khochanskiy, D., Moya-Pérez, A., Peterson, V., Rea, K., Murphy, K., Makarova, O., Buravkov, S., Hyland, N. P., Stanton, C., Clarke, G., Gahan, C. G. M., Dinan, T. G., & Cryan, J. F. (2017). Microbiota-related changes in bile acid & tryptophan metabolism are associated with gastrointestinal dysfunction in a mouse model of autism. EBioMedicine, 24, 166–178. DOI: https://doi.org/10.1016/j.ebiom.2017.09.020
  36. Israelyan, N., & Margolis, K. G. (2019). Reprint of: Serotonin as a link between the gut-brain-microbiome axes in autism spectrum disorders. Pharmacological Research, 140, 115–120. https://doi.org/10.1016/j.phrs.2018.12.023. DOI: https://doi.org/10.1016/j.phrs.2018.12.023
  37. Marler, S., Ferguson, B. J., Lee, E. B., Peters, B., Williams, K. C., McDonnell, E., Macklin, E. A., Levitt, P., Gillespie, C. H., Anderson, G. M., Margolis, K. G., Beversdorf, D. Q., & Veenstra-VanderWeele, J. (2016). Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder. Journal of Autism and Devlopment Disorders, 46(3), 1124-30.doi: 10.1007/s10803-015-2646-8. DOI: https://doi.org/10.1007/s10803-015-2646-8
  38. Abdelsalam, N. A., Hegazy, S. M., & Aziz, R. K. (2023). The curious case of Prevotella copri.Gut Microbes, 15(2), and 2249152. https://doi.org/10.1080/19490976.2023.2249152 . DOI: https://doi.org/10.1080/19490976.2023.2249152
  39. Iljazovic, A., Roy, U., Gálvez, E. J. C., Lesker, T. R., Zhao, B., Gronow, A., Amend, L., Will, S. E., Hofmann, J. D., Pils, M. C., Schmidt-Hohagen, K., Neumann-Schaal, M., & Strowig, T. (2021). Perturbation of the gut microbiome by Prevotella spp. enhances host susceptibility to mucosal inflammation. Mucosal Immunology,14(1), 113–124. https://doi.org/10.1038/s41385-020-0296-4. DOI: https://doi.org/10.1038/s41385-020-0296-4
  40. Pusceddu, M. M., El Aidy, S., Crispie, F., O’Sullivan, O., Cotter, P., Stanton, C., Kelly, P., Cryan, J. F., & Dinan, T. G. (2015). N-3 polyunsaturated fatty acids (PUFAs) reverse the impact of early-life stress on the GM. PloS One, 10(10), e0139721. https://doi.org/10.1371/journal.pone.0139721. DOI: https://doi.org/10.1371/journal.pone.0139721
  41. Cox, L. M., Yamanishi, S., Sohn, J., Alekseyenko, A. V., Leung, J. M., Cho, I., Kim, S. G., Li, H., Gao, Z., Mahana, D., Zárate Rodriguez, J. G., Rogers, A. B., Robine, N., Loke, P., & Blaser, M. J. (2014). Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell, 158(4), 705–721. https://doi.org/10.1016/j.cell.2014.05.052 DOI: https://doi.org/10.1016/j.cell.2014.05.052
  42. Deal, A., Cooper, N., Kirse, H. A., Uneri, A., Raab-Graham, K., Weiner, J. L., & Solberg Woods, L. C. (2021). Early life stress induces hyperactivity but not increased anxiety-like behavior or ethanol drinking in outbred heterogeneous stock rats. Alcohol (Fayetteville, N.Y.),91, 41–51. https://doi.org/10.1016/j.alcohol.2020.11.007 DOI: https://doi.org/10.1016/j.alcohol.2020.11.007
  43. Belcher, H. L., Morein-Zamir, S., Stagg, S. D., & Ford, R. M. (2023). Shining a Light on a Hidden Population: Social Functioning and Mental Health in Women Reporting Autistic Traits But Lacking Diagnosis. Journal of Autism and Developmental Disorders, 53(8), 3118–3132. https://doi.org/10.1007/s10803-022-05583-2 DOI: https://doi.org/10.1007/s10803-022-05583-2
  44. Garay, P. A., Hsiao, E. Y., Patterson, P. H., & McAllister, A. K. (2013). Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development. Brain, Behavior, and Immunity, 31, 54–68. https://doi.org/10.1016/j.bbi.2012.07.008 DOI: https://doi.org/10.1016/j.bbi.2012.07.008
  45. Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005). Neuroglial activation and neuroinflammation in the brain of patients with autism. Annals of Neurology, 57(1), 67–81. https://doi.org/10.1002/ana.20315. DOI: https://doi.org/10.1002/ana.20315
  46. Chen, Z. et al.(2021). Gut microbial profile is associated with the severity of social impairment and IQ performance in children with autism spectrum disorder. Front. Psychiatry,12, 789864. https://doi.org/10.3389/fpsyt.2021.789864 DOI: https://doi.org/10.3389/fpsyt.2021.789864
  47. Strati, F. et al. (2017).New evidences on the altered GM in autism spectrum disorders. Microbiome ,5. h t t p s : / / d o i . o r g / 1 0 . 1 1 8 6 / s 4 0 1 6 8 - 0 1 7 - 0 2 4 2 - 1
  48. Bhusri, B., Sutheeworapong, S., Kittichotira, W., Kusonmano, K, Thammarongtham, C., Lertampaiporn, S., Prommeenate, P., Praphanphoj, V., Kittitharaphan, W., Dulsawat, S., Paenkaew, P.& Cheevadhanarak, S.(2025) Characterization of GM on gender and age groups bias in Thai patients with autism spectrum disorder . Scientific Reports, 15,2587, https://doi.org/10.1038/s41598-025-86740-2 DOI: https://doi.org/10.1038/s41598-025-98923-y
  49. Liu, X. et al. (2023).Sex differences in the oral microbiome, host traits, and their causal relationships. Science26, 105839. h t t p s : / / d o i . o r g / 1 0 . 1 0 1 6 / j .i s c i . 2 0 2 2 . 1 0 5 8 3 9 DOI: https://doi.org/10.1016/j.isci.2022.105839
  50. Zhang, Q. et al. (2021).Comparison of GM between adults with autism spectrum disorder and obese adults. PeerJ 9, e10946. https://doi.org/10.7717/peerj.10946 DOI: https://doi.org/10.7717/peerj.10946
  51. Mashima, I. et al. (2017).exploring the salivary microbiome of children stratified by the oral hygiene index. PLoS ONE12, 0185274.https://doi.org/10.1371/journal.pone.0185274 DOI: https://doi.org/10.1371/journal.pone.0185274
  52. Ahrens, A. P. et al. (2024).Infant microbes and metabolites point to childhood neurodevelopmental disorders. Cell 187, 1853-1873 e1815. https://doi.org/10.1016/j.cell.2024.02.035 DOI: https://doi.org/10.1016/j.cell.2024.02.035
  53. Gomez, M. V. et al. (2021).Early life exposure to environmental contaminants (BDE-47, TBBPA, and BPS) produced persistent alterations in fecal microbiome in adult male mice. Toxicol. Sci.,179, 14–30. https://doi.org/10.1093/toxsci/kfaa161 DOI: https://doi.org/10.1093/toxsci/kfaa161
  54. Thoene, M., Dzika, E., Gonkowski, S. & Wojtkiewicz, J. (2020).Bisphenols in food causes hormonal and obesogenic effects comparable to or worse than bisphenol A: A literature review. Nutrients,12.https://doi.org/10.3390/nu12020532 DOI: https://doi.org/10.3390/nu12020532
  55. Fasano, A. (2012). “Leaky Gut and Autoimmune Diseases.” Clinical Reviews in Allergy & Immunology,42, ( 1), 71–78. https:// doi. org/ 10.1007/ s1201 6-011-8291-x. DOI: https://doi.org/10.1007/s12016-011-8291-x
  56. Al-Ayadhi, L., Zayed, N., Bhat, R.S., Moubayed, N.M.S., Al-Muammar, M.N. and El-Ansary,A. (2021).The use of biomarkers associated with leaky gut as a diagnostic tool for early intervention in autism spectrum disorder: A systematic review. Gut Pathog, 13, 54. DOI: https://doi.org/10.1186/s13099-021-00448-y
  57. Buie, T. (2015). “Potential Etiologic Factors of Microbiome Disruption in Autism.” Clinical Therapeutics,37( 5), 976–983. https:// doi. org/ 10.1016/j. clint hera. 2015. 04. 001. DOI: https://doi.org/10.1016/j.clinthera.2015.04.001
  58. Onore, C., M. Careaga, and P. Ashwood. (2012). “The Role of Immune Dysfunction in the Pathophysiology of Autism.” Brain, Behavior, and Immunity,26( 3), 383–392. https:// doi. org/ 10. 1016/j. bbi. 2011. 08. 007. DOI: https://doi.org/10.1016/j.bbi.2011.08.007
  59. Yoo, M. H., T. Y. Kim, Y. H. Yoon, and J. Y. Koh. (2016). “Autism phenotypes in ZnT3 Null Mice: Involvement of Zinc Dyshomeostasis, MMP-9Activation and BDNF Upregulation.” Scientific Reports,6, 28548. https:// doi. org/ 10. 1038/ srep2 8548. DOI: https://doi.org/10.1038/srep28548
  60. Li F., Ke H. , Wang S. , Mao W., Fu C, Chen X , Fu Q ., Qin X., Huang Y., Li B. , Li S. , Xing J., Wang M., Deng W. (2023).Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide Mediated Toll Like Receptor 4–Myeloid Differentiation Factor 88–Nuclear Factor Kappa B Signaling Pathway. Neurosci. Bull. 39(6),911–928.https://doi.org/10.1007/s12264-022-00993-9. DOI: https://doi.org/10.1007/s12264-022-00993-9
  61. de Magistris, L., Familiari, V., Pascotto ,A., Sapone, A., Frolli, A., Iardino, P, et al.(2010).Alterations of the IB in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr, 51, 418–424.
  62. D’Eufemia, P., Celli, M., Finocchiaro, R., Pacifico, L., Viozzi, L., Zaccagnini, M., et al. (1996) Abnormal IP in children with autism. Acta Paediatr, 85, 1076–1079. DOI: https://doi.org/10.1111/j.1651-2227.1996.tb14220.x
  63. Horvath, K., Papadimitriou, J.C., Rabsztyn, A., Drachenberg, C. and Tildon, J.T. (1999). Gastrointestinal abnormalities in children with autistic disorder. J Pediatr, 135, 559–563. DOI: https://doi.org/10.1016/S0022-3476(99)70052-1
  64. Fond, G., Boukouaci, W., Chevalier, G., Regnault, A., Eberl, G., Hamdani, N., et al.(2015).The “psychomicrobiotic”: Targeting microbiota in major psychiatric disorders: A systematic review. Pathologiebiologie, 63, 35–42. DOI: https://doi.org/10.1016/j.patbio.2014.10.003
  65. El-Ansary, A. and Al-Ayadhi, L. (2014). Relative abundance of short chain and polyunsaturated fatty acids in propionic acid-induced autistic features in rat pups as potential markers in autism. Lipids Health Dis, 13, 140. DOI: https://doi.org/10.1186/1476-511X-13-140
  66. Lucchina, L., Depino, A.M. (2014).Altered peripheral and central inflammatory responses in a mouse model of autism. Autism Res, 7, 273–289. DOI: https://doi.org/10.1002/aur.1338
  67. de Magistris, L., Familia, V., Pascotto, A., Sapone, A., Frolli, A., Iardino, P., et al. (2010). Alterations of the IB in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr, 51,418–424 DOI: https://doi.org/10.1097/MPG.0b013e3181dcc4a5
  68. Esnafoglu, E., Cırrık, S., Ayyıldız, S.N. Erdil, A., Erturk, E.Y., Daglı, A.,et al.(2017).Increased serum zonulin levels as an IP marker in autistic subjects. J Pediatr, 188, 240–244. DOI: https://doi.org/10.1016/j.jpeds.2017.04.004
  69. Kelly, J.R., Kennedy,P.J., Cryan, J.F., Dinan, T.G., Clarke, G.and Hyl N.P. (2015).Breaking down the barriers: The gut microbiome, IP and stress-related psychiatric disorders. Front Cell Neurosci, 9, 392. DOI: https://doi.org/10.3389/fncel.2015.00392
  70. Santocchi, E., Guiducci, L., Fulceri, F., Billeci, L., Buzzigoli, E., Apicella, F., et al.(2016).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, 16,183. DOI: https://doi.org/10.1186/s12888-016-0887-5
  71. Płociennikowska, A, H.romada-Judycka, A., Borzęcka, K. and Kwiatkowska, K. (2015) Co-operation of TLR4 and raft proteins in LPS induced pro-inflammatory signaling. Cell Mol Life Sci, 72, 557–581. DOI: https://doi.org/10.1007/s00018-014-1762-5
  72. Matta, S.M., Hill-Yardin, E.L., Crack, P.J. (2019).The influence of neuroinflammation in autism spectrum disorder. Brain Behav Immun, 79, 75–90. DOI: https://doi.org/10.1016/j.bbi.2019.04.037
  73. Greene, R.K., Walsh, E., Mosner, M.G., Dichter, G.S. (2019).A potential mechanistic role for neuroinflammation in reward processing impairments in autism spectrum disorder. Biol Psychol, 142, 1–12 DOI: https://doi.org/10.1016/j.biopsycho.2018.12.008
  74. Błażewicz, A., and Grabrucker. A. M. (2022). “Metal Profiles in Autism Spectrum Disorders: A Crosstalk Between Toxic and Essential Metals.”International Journal of Molecular Sciences,24(1), 308. https:// doi. org/ 10. 3390/ ijms2 4010308. DOI: https://doi.org/10.3390/ijms24010308
  75. Yasuda, H., and Tsutsui. T. (2013). “Assessment of Infantile Mineral Imbalances in Autism Spectrum Disorders (ASDs).” International Journal of Environmental Research and Public Health 10(11), 6027–6043. https:// doi. org/ 10. 3390/ ijerp h1011 6027. DOI: https://doi.org/10.3390/ijerph10116027
  76. Farina, M., and Aschner. M. (2019). “Glutathione Antioxidant System and Methylmercury-Induced Neurotoxicity: An Intriguing Interplay.” Biochimica et Biophysica Acta –General Subjects,1863(12), 129285. https:// doi. org/ 10. 1016/j. bbagen. 2019. 01. 007. DOI: https://doi.org/10.1016/j.bbagen.2019.01.007
  77. Frye, R. E., and Rossignol,D. A. (2011). “Mitochondrial Dysfunction Can Connect the Diverse Medical Symptoms Associated With Autism Spectrum Disorders.” Pediatric Research695 (2), 41r–47r. https://doi. org/ 10. 1203/ PDR. 0b013 e3182 12f16b DOI: https://doi.org/10.1203/PDR.0b013e318212f16b
  78. Napolioni, V., Persico, A. M. Porcelli, V.and Palmieri. L. (2011). “The mitochondrial aspartate/glutamate carrier AGC1 and calcium homeostasis: Physiological links and abnormalities in autism.Molecular Neurobiology44(1), 83–92. https:// doi. org/ 10. 1007/ s12035-011- DOI: https://doi.org/10.1007/s12035-011-8192-2
  79. Eggers, S., MidyaV., BixbyM., et al. (2023). Prenatal Lead Exposure Is Negatively Associated With the Gut Microbiome in Childhood. Frontiers in Microbiology,14, 1193919. https:// doi. org/ 10. 3389/ fmicb.2023. 1193919. DOI: https://doi.org/10.3389/fmicb.2023.1193919
  80. Han, S. J., Ha, K. H. Jeon, J. Y. Kim, H. J. Lee, K. W. and Kim.D. J. (2015). “Impact of cadmium eExposure on the association between lipopolysaccharide and metabolic syndrome.” International Journal of Environmental Research and Public Health, 12( 9), 11396–11409.https:// doi. Org/ 10. 3390/ ijerp h1209 11396. DOI: https://doi.org/10.3390/ijerph120911396
  81. Zhai, Q., Cen, S. Jiang, J. Zhao, J. Zhang, H. and Chen. W. (2019).
  82. “Disturbance of trace element and GM profiles as indicators of autism spectrum disorder: A pilot study of Chinese children.” Environmental Research, 171: ,501–509. https:// doi.org/ 10. 1016/j. envres.2019. 01. 060. DOI: https://doi.org/10.1016/j.envres.2019.01.060
  83. Shao, M., and Zhu,Y. (2020). Long-Term Metal Exposure Changes GutMicrobiota of Residents Surrounding a Mining and Smelting Area. Scientific Reports, 10(1) 4453. https:// doi. Org/ 10. 1038/ s4159 8-020-61143 -7. DOI: https://doi.org/10.1038/s41598-020-61143-7
  84. Chai, X., Chen, X. Yan, T. et al. (2024). IB impairmentinduced by gut microbiome and its metabolites in school-agechildrenwith Zinc deficiency. Nutrients,16(9), 1289. DOI: https://doi.org/10.3390/nu16091289
  85. Bakkaloglu, B., O'Roak, B. J.,Louvi, A.et al. (2008). Molecular cytogenetic analysis and resequencing of contactin associated protein-like2 in autism spectrum disorders. American Journal of Human Genetics,82(1), 165–173. https:// doi.org/ 10. 1016/j. ajhg. 2007. 09. 017. DOI: https://doi.org/10.1016/j.ajhg.2007.09.017
  86. Arking, D. E., Cutler, D. J.,Brune, C. W. et al. (2008). A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. American Journal of Human Genetics,82(1), 160–164. https:// doi. org/ 10. 1016/j. ajhg. 2007. 09. 015. DOI: https://doi.org/10.1016/j.ajhg.2007.09.015
  87. Parmeggiani, G., Buldrini, B., Fini, S.,Ferlini, A.and Bigoni. S.(2018). A new 3p14.2 microdeletion in a patient with intellectual disability and language impairment. Case Report and Review of the Literature. Mol Syndromol,9(4), 175–181. https:// doi. org/ 10. 1159/ 00048 9842. DOI: https://doi.org/10.1159/000489842
  88. Tan, Q., Orsso, C.E., Deehan, E.C., Kung, J.Y., Tun, H.M.,Wine, E., Madsen, K.L., Zwaigenbaum, L., Haqq, A.M. (2021).Probiotics, prebiotics, synbiotics, and fecal micrombiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review. Autism Res., 14, 1820–1836. [CrossRef]. DOI: https://doi.org/10.1002/aur.2560
  89. Abuaish, S., Al-Otaibi, N.M., Abujamel, T.S., Alzahrani, S.A., Alotaibi, S.M., Alshawakir, Y.A., Aabed, K., El-Ansary, A. (2021).Fecal transplant and Bifidobacterium treatments modulate gut Clostridium bacteria and rescue social impairment and hippocampal BDNFexpression in a rodent model of autism. Brain Sci., 11, 1038. [CrossRef]. DOI: https://doi.org/10.3390/brainsci11081038
  90. Wong, C.B., Odamaki, T., Xiao, J.-Z. (2019).Beneficial effects of Bifidobacterium Longum Subsp. Longum BB536 on human health:Modulation of gut microbiome as the principal action. J. Funct. Foods, 54, 506–519. [CrossRef] DOI: https://doi.org/10.1016/j.jff.2019.02.002
  91. Finegold, S.M., Dowd, S.E.; Gontcharova, V.; Liu, C.; Henley, K.E.; Wolcott, R.D.; Youn, E.; Summanen, P.H.; Granpeesheh,D.; Dixon, D.; et al. Pyrosequencing Study of Fecal Microflora of Autistic and Control Children. Anaerobe 2010, 16, 444–453.[CrossRef] [PubMed] DOI: https://doi.org/10.1016/j.anaerobe.2010.06.008
  92. 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, e76993. [CrossRef] [PubMed] DOI: https://doi.org/10.1371/journal.pone.0076993
  93. Sauer, A.K., Bockmann, J., Steinestel, K., Boeckers, T.M., Grabrucker, A.M. (2019) .Altered intestinal morphology and microbiota composition in the autism spectrum disorders associated SHANK3 mouse model. Int. J. Mol. Sci., 20, 2134. [CrossRef]. DOI: https://doi.org/10.3390/ijms20092134
  94. Ding, X., Xu, Y., Zhang, X., Zhang, L., Duan, G., Song, C., Li, Z.,Yang, Y., Wang, Y., Wang, X. et al. (2020).GM changes in Patients with autism spectrum disorders. J. Psychiatr. Res., 129, 149–159. [CrossRef] [PubMed]. DOI: https://doi.org/10.1016/j.jpsychires.2020.06.032
  95. Guo, P.,Zhang, K., Ma, X., He, P. (2020).Clostridium Species as Probiotics: Potentials and Challenges. J. Anim. Sci. Biotechnol., 11, 24. [CrossRef] DOI: https://doi.org/10.1186/s40104-019-0402-1
  96. Nagano, Y., Itoh, K., Honda, K. (2012).The Induction of Treg cells by gut-indigenous Clostridium. Curr. Opin. Immunol., 24, 392–397. [CrossRef] DOI: https://doi.org/10.1016/j.coi.2012.05.007
  97. Hold, G.L., Pryde, S.E.,Russell, V.J., Furrie, E., Flint, H.J. (2002).Assessment of microbial diversity in human colonic samples by 16S RDNA sequence analysis. FEMS microbiol. Ecol., 39, 33–39. [CrossRef]. DOI: https://doi.org/10.1111/j.1574-6941.2002.tb00904.x
  98. Adams, J.B., Audhya, T., McDonough-Means, S., Rubin, R.A., Quig, D.; Geis, E.,Gehn, E., Loresto, M., Mitchell, J., Atwood, S.et al. (2011).Effect of vitamin/mineral supplement on children and adults with autism. BMC Pediatr., 11, 111. DOI: https://doi.org/10.1186/1471-2431-11-111
  99. Gvozdjáková, A., Kucharská, J., Ostatníková, D., Babinská, K., Nakládal, D., Crane, F.L. (2014).Ubiquinol improves symptoms in children with autism. Oxid. Med. Cell. Longev., 798957. DOI: https://doi.org/10.1155/2014/798957
  100. van Sadelhoff, J.H.J., Pardo, P.P., Wu, J., Garssen, J., van Bergenhenegouwen, J., Hogenkamp, A., Hartog, A., Kraneveld, A.D. (2019).The Gut-Immune-Brain Axis in Autism Spectrum Disorders; a Focus on Amino Acids. Front. Endocrinol., 10, 247. DOI: https://doi.org/10.3389/fendo.2019.00247
  101. Rossignol, D.A., Frye, R.E. (2021).The effectiveness of cobalamin (B12) treatment for autism spectrum disorder: A systematic review and meta-analysis. J. Pers. Med., 11, 784. DOI: https://doi.org/10.3390/jpm11080784
  102. Bravo, J.A., Forsythe, P., Chew, M.V., Escaravage, E.,Savignac, H.M., Dinan, T.G., Bienenstock, J., Cryan, J.F. (2011).Ingestion of Lactobacillus Strain Regulates Emotional Behavior and Central GABA Receptor Expression in a Mouse via the Vagus Nerve. Proc. Natl. Acad. Sci. USA, 108, 16050–16055. [CrossRef] DOI: https://doi.org/10.1073/pnas.1102999108
  104. Mensi, M.M., Rogantini, C., Marchesi, M., Borgatti, R.,Chiappedi, M. (2021).Lactobacillus Plantarum PS128 and other probiotics in children and adolescents with autism spectrum disorder: areal-world experience. Nutrients, 13, 2036. [CrossRef]. DOI: https://doi.org/10.3390/nu13062036
  105. Santocchi, E., Guiducci, L., Prosperi, M., Calderoni, S., Gaggini, M.,Apicella, F., Tancredi, R., Billeci, L., Mastromarino, P., Grossi,E., et al. (2020).Effects of probiotic supplementation on gastrointestinal, senso(ry and core symptoms in autism spectrum disorders:A randomized controlled trial. Front. Psychiatry, 11, 550593. [CrossRef] [PubMed]. DOI: https://doi.org/10.3389/fpsyt.2020.550593
  106. Grossi, E., Melli, S., Dunca, D., Terruzzi, V. (2016).Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics. SAGE Open Med. Case Rep., 4, 2050313X16666231. [CrossRef] [PubMed]. DOI: https://doi.org/10.1177/2050313X16666231
  107. Tomova, A., Husarova, V.,Lakatosova, S., Bakos, J., Vlkova, B., Babinska, K., Ostatnikova, D. (2015).Gastrointestinal microbiota in children with autism in Slovakia. Physiol. Behav., 138, 179–187. [CrossRef]/ DOI: https://doi.org/10.1016/j.physbeh.2014.10.033
  108. He, X.; Liu, W., Tang, F., Chen, X., Song, G. (2023).Effects of probiotics on autism
  109. spectrum disorder in children: A systematic review and meta-analysis of clinical trials. Nutrients, 15, 1415. [CrossRef] DOI: https://doi.org/10.3390/nu15061415
  110. Alam, S., Westmark, C. J. and McCullagh. E. A. (20220. Diet in Treatmentof autism spectrum disorders. Frontiers in Neuroscience16, 1031016.https:// doi. org/ 10. 3389/ fnins. 2022. 1031016 DOI: https://doi.org/10.3389/fnins.2022.1031016
  111. Alsubaiei, S. R. M., Alfawaz, H. A.,Bhat, R. S. and El-Ansary. A. (2023). Nutritional intervention as a complementary neuroprotective approach against propionic acid-induced neurotoxicity and associated biochemical autistic features in rat pups. Metabolites,13(6)738. https:// doi. org/ 10. 3390/ metab o1306 0738. DOI: https://doi.org/10.3390/metabo13060738
  112. Usama, U., Khan, M.and FatimaS. (2018). Role of Zinc in shaping the gut microbiome; proposedmechanisms and evidence from the literature. Journal of Gastrointestinal & Digestive System, 8, 1000548. https:// doi. org/ 10. 4172/ 2161-069X. 1000548.
  113. Xia, P., Lian, S. Wu, Y. Yan, L. Quan, G.and Zhu. G. (2021). “Zinc is an important inter-kingdom signal between the host and microbe.Veterinary Research, 52(1), 39. https:// doi. org/ 10. 1186/ s1356 7-021-00913-1. DOI: https://doi.org/10.1186/s13567-021-00913-1

Downloads

Download data is not yet available.

Similar Articles

1-10 of 15

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)

1 2 > >>