Prebiotic

The Role of the Gut Microbiome in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a complex biological neurodevelopmental disorder that is estimated to affect 1 in 100 children worldwide (World Health Organization (WHO)., 2023). Due to its broad-spectrum, signs often have a high individual variability, however, those with ASD commonly have difficulties relating to social, behavioural and communication skills (WHO., 2023). Gastrointestinal symptoms, such as abdominal pain, flatulence and bloating, are often a comorbidity in those with ASD, however, the underlying cause is unknown. Research suggests that gastrointestinal complaints and neuro-behavioural traits in ASD could be linked to gut microbiome composition and via the two-way communication between the gut and brain, called the gut-brain axis (Fattorusso et al., 2019). In this Research Spotlight, we will explore ASD in relation to the gut microbiome and delve into a study looking at the impact of Bimuno® GOS on 30 children with ASD (Grimaldi et al., 2018).

Gut-brain connection

It is well known that the gut microbiome plays an important role in health (de Vos et al., 2022). The gut-brain axis, in particular, has been of increasing interest due to its ability to impact gastrointestinal function, mood and cognitive health (Appleton., 2018). As research has progressed and more is understood about the gut-brain connection it is thought that this could explain some of the neurodevelopmental deficits and comorbid gastrointestinal disturbances seen in ASD (Li et al., 2016).

Those with ASD often have alterations in their gut microbiome profiles that are consistent with dysbiosis, however, it is not yet known the distinct microbiome profile that is specific to individuals with ASD (Fattorusso et al., 2019). Interestingly, research has revealed that Clostridiumbacteria are often overabundant in the colons of those with ASD compared to neurotypical individuals and could be associated with certain autistic traits and comorbidities (Kandeel et al., 2020). In particular, those with ASD exhibit high levels of Clostridium difficileand Clostridium clostridioformenot found in neurotypical children, and these strains are considered to be pathogenic strains of bacteria with opportunistic characteristics (Dehoux et al., 2016; Kandeel et al., 2020; Khanna and Gupta., 2019).

ASD and GI complaints

Common gastrointestinal complaints reported in those with ASD, such as constipation, diarrhoea and abdominal pain, are associated with changes in the composition of the gut microbiome (Ristori et al., 2019). Many functional gastrointestinal disorders that feature these common issues have been linked to the gut microbiome and a lower abundance of beneficial bacteria, such as bifidobacteria (Ristori et al., 2019). Along with higher levels of Clostridiumbacteria, many children with ASD also have a lower relative abundance of bifidobacteria in the gut, suggesting a possible link between the gut microbiome and comorbidities of ASD (Argou-Cardozo and Zeidán-Chuliá., 2018; Ristori et al., 2019).

Children with ASD who also have comorbid gastrointestinal disturbances tend to exhibit more severe behavioural changes, such as irritability and social withdrawal, and these neurobehavioural symptoms are thought to have an underlying inflammatory pathophysiology (Fattorusso et al., 2019). The inflammation hypothesis in ASD suggests the presence of immune system dysfunction in its development (Hughes et al., 2022). Up to 80% of immune cells are found in the gut, and gut barrier function plays a key role in immune homeostasis (Wiertsema et al., 2021). Given that gut barrier integrity and function can be influenced by gut microbiome composition and crosstalk along the gut-brain axis, it is important to note that dysbiosis, such as what is seen in ASD, can lead to changes in immune system function (Erbescu et al., 2022; Levy et al., 2017).

Research Spotlight: ASD and Bimuno® GOS

In this Research Spotlight, we highlight a study looking at the effects of different diets and supplementation with Bimuno® GOS in autistic children across a 10-week period (Grimaldi et al., 2018). This randomised, double-blind, placebo-controlled parallel study saw 30 children aged 4-11 years with ASD divided into two dietary groups: one excluding gluten and casein (exclusion group) and one group without restriction (non-exclusion). These groups were further divided into another 2 groups and supplemented with either Bimuno® GOS or placebo (maltodextrin) for 6-weeks. The protocol followed a 2-week run-in, 6-week feeding period and a 4-week follow-up. Throughout the protocol, gastrointestinal symptoms, such as abdominal pain, flatulence and bloating were recorded daily, along with weekly faecal samples. At the end of each stage of the study, questionnaires were filled out by the children’s caregivers to assess behaviour – Autism Treatment Evaluation Checklist (ATEC), The Spence Children’s Anxiety Scale subscale-P (parent-report), the Autism Spectrum Quotient (AQ) and the Empathizing Quotient/Systemizing Quotient (EQ-SQ).

The results showed a significant change in anti-sociability scores in those consuming an exclusion diet in combination with Bimuno® GOS (Grimaldi et al., 2018). These results support the hypothesis that the gut microbiome could be implicated in the pathophysiology of ASD and as such, should be of consideration in future research.

Read the full open access paper here:

A prebiotic intervention study in children with autism spectrum disorders (ASDs) | Microbiome (springer.com)

References

Agirman, G., Yu, K.B. and Hsiao, E.Y. (2021). Signaling inflammation across the gut-brain axis. Science, [online] 374(6571), pp.1087–1092. Available at: https://www.science.org/doi/10.1126/science.abi6087#:~:text=Inflammatory%20signaling%20occurs%20across%20the%20gut-brain%20axis%20in,homeostasis%20or%20amplify%20inflammation%20in%20a%20context-dependent%20manner..

Appleton, J. (2018). The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health. Integrative Medicine: A Clinician’s Journal, [online] 17(4), pp.28–32. Available at:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469458/.

Argou-Cardozo, I. and Zeidán-Chuliá, F. (2018). Clostridium Bacteria and Autism Spectrum Conditions: A Systematic Review and Hypothetical Contribution of Environmental Glyphosate Levels. Medical sciences (Basel, Switzerland), [online] 6(2), p.29. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29617356 [Accessed 4 Nov. 2019].

British Society for Immunology (n.d.). Immunity in the Gut | British Society for Immunology. [online] www.immunology.org. Available at: https://www.immunology.org/public-information/bitesized-immunology/organs-tissues/immunity-gut.

Dehoux, P., Marvaud, J.C., Abouelleil, A., Earl, A.M., Lambert, T. and Dauga, C. (2016). Comparative genomics of Clostridium bolteae and Clostridium clostridioforme reveals species-specific genomic properties and numerous putative antibiotic resistance determinants. BMC Genomics, [online] 17(1). Available at:https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-016-3152-x.

de Vos, W., Tilg, H., Van Hul, M. and Cani, P. (2022). Gut microbiome and health: mechanistic insights. Gut, [online] 71(5), pp.1020–1032. Available at:https://gut.bmj.com/content/71/5/1020.

Erbescu, A., Sorina Mihaela Papuc, BudiÅŸteanu, M., Arghir, A. and Neagu, M. (2022). Re-emerging concepts of immune dysregulation in autism spectrum disorders. Frontiers in Psychiatry, [online] 13. Available at: https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.1006612/full.

Fattorusso, A., Di Genova, L., Dell’Isola, G., Mencaroni, E. and Esposito, S. (2019). Autism Spectrum Disorders and the Gut Microbiota. Nutrients, [online] 11(3), p.521. Available at: https://www.mdpi.com/2072-6643/11/3/521 [Accessed 3 Apr. 2024].

Grimaldi, R., Gibson, G.R., Vulevic, J., Giallourou, N., Castro-Mejía, J.L., Hansen, L.H., Gibson, E.L., Nielsen, D.S. and Costabile, A. (2018). A prebiotic intervention study in children with autism spectrum disorders (ASDs). Microbiome, [online] 6(1), pp.1–13. Available at: https://doaj.org/article/46b7e6bb59b24362bea60bb069c23f79.

Hughes, H.K., R.J.Moreno and Ashwood, P. (2022). Innate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD). Brain, Behavior, and Immunity. [online] Available at: https://www.sciencedirect.com/science/article/pii/S0889159122004597#:~:text=Multiple%20hypotheses%20converge%20to%20suggest%20that%20neuroinflammation%2C%20or,seen%20in%20ASD%2C%20often%20associated%20with%20worsening%20behaviors..

Kandeel, W.A., Meguid, N.A., Bjørklund, G., Eid, E.M., Farid, M., Mohamed, S.K., Wakeel, K.E., Chirumbolo, S., Elsaeid, A. and Hammad, D.Y. (2020). Impact of Clostridium Bacteria in Children with Autism Spectrum Disorder and Their Anthropometric Measurements. Journal of Molecular Neuroscience. [online] Available at:https://pubmed.ncbi.nlm.nih.gov/32130666/#:~:text=Children%20with%20ASD%20had%20two%20types%20of%20Clostridium,%28Clostridium%20tertium%29%20not%20found%20in%20the%20ASD%20children..

Khanna, S. and Gupta, A. (2014). Community-acquired Clostridium difficile infection: an increasing public health threat. Infection and Drug Resistance, [online] p.63. Available at:https://www.tandfonline.com/doi/full/10.2147/IDR.S46780.

Levy, M., Kolodziejczyk, A.A., Thaiss, C.A. and Elinav, E. (2017). Dysbiosis and the immune system. Nature Reviews Immunology, [online] 17(4), pp.219–232. Available at: https://www.nature.com/articles/nri.2017.7.

Li, Q., Han, Y., Dy, A.B.C. and Hagerman, R.J. (2017). The Gut Microbiota and Autism Spectrum Disorders. Frontiers in Cellular Neuroscience, [online] 11. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408485/.

Li, Q. and Zhou, J.-M. . (2016). The microbiota–gut–brain axis and its potential therapeutic role in autism spectrum disorder. Neuroscience, [online] 324, pp.131–139. doi:https://doi.org/10.1016/j.neuroscience.2016.03.013.

Ristori, M.V., Quagliariello, A., Reddel, S., Ianiro, G., Vicari, S., Gasbarrini, A. and Putignani, L. (2019). Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions. Nutrients, [online] 11(11), p.2812. Available at:https://www.mdpi.com/2072-6643/11/11/2812.

Wiertsema, S.P., van Bergenhenegouwen, J., Garssen, J. and Knippels, L.M.J. (2021). The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients, [online] 13(3), p.886. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001875/.

World Health Organization (2023). Autism spectrum disorders. [online] Who.int. Available at: https://www.who.int/news-room/fact-sheets/detail/autism-spectrum-disorders.