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Autism is one of the fastest-growing neuro-difference diagnoses in the world, thanks to improved awareness and screening, but a vast majority of autistic individuals experience gastrointestinal symptoms. Many studies have shown that dysbiosis and changes in the human gut microbiome are implicated in the development of symptoms. Here, we explore a recent study that investigated the effect of HMOs (supplied by Layer Origin) on the gastrointestinal (GI) symptoms of autistic children compared to another common prebiotic, inulin.
The World Health Organization predicts that around 1 in 100 children globally is autistic, although this figure is likely to be substantially higher[i]. Although it has been characterized as a neurodevelopmental disorder, encompassing a broad range of cognitive, behavioral, and communication differences[ii], more nuanced research has identified clear links between autism and the gut microbiome[iii]. Meaning that the gut should not be disregarded as a potential therapeutic target for autistic individuals.
With that in mind, Mittal and colleagues (2024) compared the effects of two important prebiotics, inulin and human milk oligosaccharides (HMOs) in managing gastrointestinal issues in autistic children. We discuss the outcome of their study here.
Autism is one of the fastest-growing neurological differences across the world thanks to increased awareness and screening. In the US, the Centers for Disease Control and Prevention (CDC) estimates that 1 in 68 children are autistic, a figure way above the predicted average purported by the WHO[iv].
Although autism is a neuro-difference, the gut microbiome has also been linked to autism, particularly as an exclusive type of gastrointestinal inflammation has been witnessed in autistic children[v].
Furthermore, the gut-brain axis, a unique bi-directional communication pathway between the brain and the gut, demonstrates that the colonic ecosystem can influence many neurological disorders including Alzheimer’s disease, Parkinson’s disease, and autism.
Many autistic people experience gastrointestinal symptoms, including:
For this reason, some studies indicate that targeting the gut microbiota and modulating the overall composition and diversity could offer new therapeutic options for autistic people[vi].
Read more about autism and its association with the gut in our blog.
As discussed, gut microbiome changes are implicated in autism. Some of the reported changes are:
These changes lead to the movement of these bacteria, their metabolites, and toxins, and these changes become even more significant following the use of antibiotics. This opens up the question of whether the gut microbiota in autistic individuals can be changed by external factors like antibiotics, can it be manipulated positively with prebiotics?
Recent research has investigated the effect of pre-and probiotics in autism. Zhang et al (2024) summarised that prebiotics and probiotics are beneficial for autism but more research needs to be conducted to understand how bacterial metabolites influence the balance of the gut[vii]. Some of the possible ways that prebiotics and probiotics interact with autism spectrum disorder are shown in Figure 1.
Source: Zhang et al (2024)
Figure 1.Some of the possible mechanisms that prebiotics and probiotics adopt to manipulate the gut microbiome and influence autism spectrum disorder.
Grimaldi and colleagues (2018) explored the effect of prebiotics and gluten and casein-free diets in autistic children. Their research showed that following an exclusion diet for 6 weeks resulted in fewer incidences of abdominal pain and bowel movements and an increase in Faecalibacterium prausnitzii and Bacteroides abundance. An intervention with the prebiotic Bimuno® Galactooligosaccharides (B-GOS) resulted in improvements in antisocial behavior and significant increases in bacteria from the Lachnospiraceae family. Therefore, suggesting that a combination of exclusion diets and prebiotics could manipulate the microbiome and improve some behavioral traits[viii].
Besides GOS, inulin and HMOs are also popular prebiotics associated with several beneficial health properties. HMOs are one of the main constituents of human breast milk and are linked to development during infancy, immunity, and promoting gut health. They can increase the abundance of beneficial species such as Bifidobacteria and promote balance in the gut. Inulin, on the other hand, is found in plant foods such as beans, root vegetables, and cereals, and has also been linked to promoting the growth of beneficial bacteria. So, Mittal et al (2024) compared the effects of these two popular and well-researched prebiotics, HMOs and inulin, in managing gut issues in autistic children.
The study by Mittal et al (2024) was an open randomized open trial. Sixty children aged between 4 and 10 years old who had been diagnosed with autism and experienced gut-related issues were enrolled and randomly assigned to one of two groups, Group A and Group B. Each group consisted of 30 participants and were assigned as follows:
|
Group A |
1g daily of PureHMO for children containing 800 mg 2’-Fucosyllactose and Lacto-N-neotetraose (LNnT) (supplied by Layer Origin) |
|
Group B |
0.9 g daily of Certified Organic Inulin (pure prebiotic powder) |
Every participant was reviewed by telephone every 15 days for compliance and abdominal symptoms were included according to the Rome III criteria for functional gastrointestinal disorders, as shown below:
|
S. No |
Abdominal Symptom |
Details: In the past 2 months, how often did your child experience the following |
|
1 |
Diarrhea |
a. Passing 1-2 episodes of loose watery stools without smell/day b. Passing episodes of loose watery stools with smell /day c. Passing more than 2 episodes of loose watery stools /day d. Does the diarrhea last for more than 5 days |
|
2 |
Constipation |
a. Does the child pass stools comfortably daily without pain and pressure? b. Does the child feel pain/apply pressure while passing stools? c. Does the child complaints of hard lump-like stools (consistency of stools) d. Does the child pass stools every 2 to 4 days (how often does it happen?) |
|
3 |
Abdominal Pain |
a. Does the pain remain continuous throughout the day? b. Is the pain severe enough to affect his/her daily routine activities (learning, academics, ADL activities of daily routine.) c. Does the pain come in intervals? (Colicky-does it gets worse after eating meals) d. How often is the belly pain associated with vomiting/reflex issues? |
|
4 |
Vomiting/Reflux |
a. How often did your child vomit/throw up? b. How often did your child nauseated but did not vomit? c. How often did your child experience a burning sensation (c/o pain in the upper chest)? d. How often did your child experience nausea before vomiting |
|
5 |
Bloating |
a. Burp (belch) again and again without vomiting? b. Pass a lot of gas very frequently? c. Develop a swollen belly during the day (belly that sticks out more than usual). d. Swollen or gulp extra air? (you might hear a clicking noise when your child swallows)
|
Table 1.The abdominal symptoms included in the study according to the Rome III criteria.
Following allocation to a group, baseline data was collected at the beginning of the study and the end of the 12-week intervention.
The main results of the study by Mittal and Co. (2024) are summarised below:
|
Symptom |
Comparative observations between HMO and inulin groups |
|
Diarrhea |
|
|
Constipation |
|
|
Abdominal Pain |
|
|
Vomiting |
|
|
Bloating |
|
One of the biggest findings of the study was the significant reduction in the ROME III Criteria Total Scores, a scoring system usually used to diagnose irritable bowel syndrome (IBS), in the HMO group compared to the inulin group (Figure 2.).
Figure 2.There was a significant decrease in the ROME III scores in the HMO group compared to the inulin group. The scores fell by 11.6 in the HMO group compared to just 2.24 in the inulin group.
The study demonstrates that HMOs can significantly improve the gastrointestinal symptoms in children with autism, particularly:
Overall, this shows that HMOs are better than inulin for treating gut-related autism symptoms. The prevalence of gastrointestinal symptoms in autistic people is thought to be anywhere between 9 and 91% with children being up to four times more likely to experience functional GI symptoms[ix].
Dysbiosis, or an imbalance in microbiota, is believed to be fundamental in autism[x] which can be seen in Figure 3.
Figure 3.The image shows how an imbalanced gut microbiome where pathogenic microbes outnumber health-promoting bacteria, including Bifidobacteriaand Lactobacilluscan contribute to a leaky gut in autistic children. Here, pathogenic bacteria bind to glycan receptors along the mucosal barrier affecting its integrity and allowing pathogenic microbes to pass through. Once they have ‘scaled the wall’, the pathogens initiate a cascade of immune responses including the release of inflammatory cytokines. Altogether these gastrointestinal features are believed to contribute to the development of autistic features through the gut-brain axis[xi].
Human milk oligosaccharides can help to plug a leaky gut. Šuligoj et al (2020) found that a combination of the HMOs 2’-FL and LNnT increased the abundance of Bifidobacteriaand the production of health-promoting short-chain fatty acids (SCFAs), particularly butyrate.[xii]
Butyrate is the main energy source for the cells that line the colon and has several important roles in strengthening the integrity of the gut barrier. Therefore, this demonstrates that HMOs can directly modulate the gut barrier function.
Mittal et al (2024) also demonstrated the important role HMOs play in tightening the gut barrier and preventing a leaky gut. Beneficial bacteria like Bifidobacteriause the HMOs to promote their growth, enable them to thrive, and increase their production of healthy metabolites.
Because the healthy bacteria grow in numbers, dysbiosis is kept at bay, and they can bind to the glycan receptors in the gut lining, preventing pathogens from binding to them instead. Ultimately, the administration of the HMOs to autistic children effectively repairs the leaky junction proteins in their intestinal lining, strengthening its integrity, and preventing pathogens from crossing over into the bloodstream (Figure 4).
Figure 4.How HMOs contribute to repairing a leaky gut in autistic children.
In other studies, HMOs have been linked to periods of increased growth and experiential learning, and greater cognitive, language, and motor skills development, particularly in infants aged 18 to 24 months, when breastfed for the first 6 months[xiii].
In this study, HMOs were shown to be more beneficial than inulin over a 12-week supplementation period for the relief of GI symptoms in autistic children. That’s because HMOs can selectively promote the growth of specific bacteria and prevent the growth of pathogenic or non-beneficial microbes. This study serves as a good foundation for larger studies to investigate the effects of HMOs in children with autism who experience gastrointestinal symptoms that affect their quality of life, and that of their parents or carers.
The study by Mittal and colleagues (2024) shows that HMOs are superior to inulin for the treatment of gastrointestinal symptoms, such as diarrhea, constipation, and abdominal pain. The HMOs used in this study were supplied by Layer Origin and included the PureHMO® Human Milk Oligosaccharide 2’-FL Super Prebiotic Powder, but our range also includes the SuperHMO® for Kids Powder which comprises 5 premium HMOs including 2’-FL and LNnT used in this study.
Written by: Leanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome.
[i] Autism [Internet]. World Health Organization; [cited 2024 Aug 7]. Available from: https://www.who.int/news-room/fact-sheets/detail/autism-spectrum-disorders
[ii] Morton, J.T., Jin, DM., Mills, R.H. et al. Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles. Nat Neurosci 26, 1208–1217 (2023). https://doi.org/10.1038/s41593-023-01361-0
[iii] Peralta-Marzal, L.N., Rojas-Velazquez, D., Rigters, D. et al. A robust microbiome signature for autism spectrum disorder across different studies using machine learning. Sci Rep 14, 814 (2024). https://doi.org/10.1038/s41598-023-50601-7
[iv] Wright J, 987B367A-C3BB-4784-AB5045143E96A4AA, /author/spectrum/, 5xhaUhtZE7TNUYsPapY5s7, Spectrum, Spectrum. The real reasons autism rates are up in the U.S. [Internet]. Scientific American; 2024 [cited 2024 Aug 7]. Available from: https://www.scientificamerican.com/article/the-real-reasons-autism-rates-are-up-in-the-u-s/
[v] Furlano RI, Anthony A, Day R, Brown A, McGarvey L, Thomson MA, Davies SE, Berelowitz M, Forbes A, Wakefield AJ, Walker-Smith JA, Murch SH. Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism. J Pediatr. 2001 Mar;138(3):366-72. doi: 10.1067/mpd.2001.111323. PMID: 11241044.
[vi] Hung, L.Y., Margolis, K.G. Autism spectrum disorders and the gastrointestinal tract: insights into mechanisms and clinical relevance. Nat Rev Gastroenterol Hepatol 21, 142–163 (2024). https://doi.org/10.1038/s41575-023-00857-1
[vii] Zhang S, Han F, Wang Q, Fan F. Probiotics and prebiotics in the treatment of autism spectrum disorder: A narrative review. Journal of Integrative Neuroscience. 2024 Jan 22;23(1):20. doi:10.31083/j.jin2301020
[viii] Grimaldi R, Gibson GR, Vulevic J, Giallourou N, Castro-Mejía JL, Hansen LH, et al. A prebiotic intervention study in children with autism spectrum disorders (ASDS). Microbiome. 2018 Aug 2;6(1). doi:10.1186/s40168-018-0523-3
[ix] Wang J, Ma B, Wang J, Zhang Z, Chen O. Global prevalence of autism spectrum disorder and its gastrointestinal symptoms: A systematic review and meta-analysis. Frontiers in Psychiatry. 2022 Aug 23;13. doi:10.3389/fpsyt.2022.963102
[x] Hughes HK, Rose D, Ashwood P. The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders. Curr Neurol Neurosci Rep. 2018 Sep 24;18(11):81. doi: 10.1007/s11910-018-0887-6. PMID: 30251184; PMCID: PMC6855251.
[xi] Al-Ayadhi, L., Zayed, N., Bhat, R.S. et al. 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 (2021). https://doi.org/10.1186/s13099-021-00448-y
[xii] Šuligoj T, Vigsnæs LK, Abbeele PVD, Apostolou A, Karalis K, Savva GM, McConnell B, Juge N. Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function. Nutrients. 2020 Sep 13;12(9):2808. doi: 10.3390/nu12092808. PMID: 32933181; PMCID: PMC7551690.
[xiii] Berger PK, Ong ML, Bode L, Belfort MB. Human Milk Oligosaccharides and Infant Neurodevelopment: A Narrative Review. Nutrients. 2023 Jan 31;15(3):719. doi: 10.3390/nu15030719. PMID: 36771425; PMCID: PMC9918893.
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August 23, 2024
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