Could probiotics help those with autism?

 Autism & digestive health

People with autism often have more digestive health problems than average. 1 in 4 children with autism are thought to have at least one chronic gastrointestinal symptom¹ and numerous studies have discovered abnormal digestive health conditions in people with autism^2,3,11. Autistic children have also been found to have more Clostridia (a type of pathogenic bacteria) in the gut than children without autism⁴ and a recently published study⁵ found a little known bacterial genus called Sutterella present in microbiota in just over half the participants with autism, but in none of those without autism. Research into the relationship between the gut microbiome and autism is ongoing¹⁴ which is good news for anyone looking for support in this area.

Some research suggests that microorganisms support digestive health in adults and children. So could live cultures help children or adults with autism?

Probiotics for autism: a look at the research

Clinical research

Probably the best known UK clinical study into probiotics for autism was the unfinished trial run in 2006 by Professor Glenn Gibson at the University of Reading; referred to by some as the trial which was "so successful, that it failed". 40 autistic children all between 4 and 13 years old were randomly separated into a trial group, and a control group. The trial group were given a probiotic supplement with the species Lactobacillus plantarum whilst children in the other group were given placebos (read about placebo-controlled studies in the Probiotics Learning Lab). The trial was supposed to continue this way for three weeks, before the groups would switch supplements and continue as such for a further three weeks. However, researchers reported that the Lactobacillus probiotics had such a positive effect on the participants, that the 'blind' aspect of the trial fell through. Parents of participants in the probiotic group could see a noticeable effect, and said it was heartbreaking to have to stop their child from taking the probiotics. Too many participants dropped out of the trial when they were supposed to switch over.

Comments from parents⁶ of participants in the probiotic group included not only reports on digestive health improvements, such as, 'better formed stools' but also potentially behavioural improvements, such as, 'more calm, relaxed' and 'improved ability to listen and concentrate'. It is certainly worth mentioning that these comments are taken from a few parents, and also that interestingly, during the trial the parents' overview of the effects of the probiotics tended to be more positive than the view of the teachers. Finally, the study saw a large drop out rate which meant it could not continue.

We have not been able to ascertain which strain of the L. plantarum species was used; reports of the trial state only that this strain was non-commercial. Research demonstrates that any beneficial effects of probiotics are strain-specific (i.e. the benefits must ideally be associated with a specific probiotic strain, and not simply a species - see Probiotics Learning Lab).

Subsequently, a 2022 article has highlighted the research on the probiotic strain L. plantarum PS128¹². Data from three different research groups have found that L. plantarum PS128 appears to be helpful in balancing levels of neurotransmitters, which in some autistic people can be imbalanced.

Clinical review

A 2017 review of clinical research⁷, by Dr. Qinrui Li from Peking University Hospital, Beijing, analysed more than 150 scientific papers, dating back as far as the 1960s, in order to ascertain the impact of taking either prebiotics or probiotics on the symptoms of Autistic Spectrum Disorders (ASD). The review which was published in the Journal ‘Frontiers in Cellular Neuroscience’ also assessed the impact of changes in diet, such as following a casein- or gluten-free diet, on the condition.

Results of the review show that improving the health of the intestinal flora eases autism symptoms and improves sufferers’ social behaviours and ability to interact. Improvements were seen with both pre- and probiotic intervention and also with elimination diets. Researchers found that the improvements to symptoms that were achieved with dietary changes were mainly as a result of reduced intestinal inflammation and therefore reduced intestinal permeability, and leaking of toxins in to the bloodstream. Improvements seen as a result of pre- and probiotic supplementation however, were thought to occur as a result of strengthened activity in areas of the brain that are responsible for emotion. Pre- and probiotics effect our emotional responses via their interaction with the gut-brain axis, however they are also known to improve the health of the intestinal lining and to help to reverse intestinal permeability. This too will have positive repercussions for the symptoms of ASD via a reduction in circulating toxins that can affect the nervous system.

Following the review Dr Li said:

'Efforts to restore the gut microbiota to that of a healthy person has been shown to be really effective. Our review looked at taking probiotics, prebiotics, changing the diet - for example, to gluten- and casein-free diets. All had a positive impact on symptoms.'

When asked how the results of the review might benefit patients in the future, she added:

'We would hope that our review leads to research on the link between the gut microbiota and ASD, and eventually a cheap and effective treatment.'

Research in animal models

Whilst there are still relatively few human clinical trials investigating the link between gut microflora and autism, scientists at Baylor College of medicine in Texas have recently been looking at the impacts of gut microflora on the behavioural development of mice. Senior study author, Dr. Mauro Costa-Mattioli, said that the inspiration for the study⁸ was taken from earlier human studies that have shown a correlation between maternal obesity during pregnancy and the risk of their offspring developing various neuro-developmental disorders, including Autistic Spectrum Disorders.

In the study, it was found that young mice born to overweight mothers showed behavioural deficits, including spending less time in contact with other young mice, and not initiating social interactions. Both of these character traits are common in autistic spectrum disorders in humans. Moreover the bacterial composition of the young mice born to overweight mothers was also different from those born to healthy-weight mothers. In particular one type of bacteria, Lactobacillus reuteri, was reduced more than nine fold in the microbiome of the mice born to the over-weight group.

Based on these findings, the research team cultured a strain of L. reuteri, and put it in the drinking water of the unhealthy high-fat-diet offspring. They found that the inclusion of this one single strain of probiotic bacteria was enough to rectify their anti-social behaviour traits. Interestingly, the research also showed that this single strain of bacteria promoted the production of a ‘bonding hormone’, which is understood to play a crucial part in social behaviour in humans. A lack of this bonding hormone in humans has been associated with autism and Autistic Spectrum Disorders.

A separate recent animal study has tried to further our understanding of the role the gut microbiome plays in influencing brain and nervous system function⁹. It was found that certain groups of bacteria seemed to have an effect on cortisol and serotonin levels. The research is still at the exploratory stage, and a lot more awaits discovery before we can have a firmer understanding of the interplay between gut and brain. Although we may still be in the dark, research is consistently showing a connection between the gut microbiome and nervous system.

More research needed

A great deal more clinical research is necessary before any firm conclusions can be made as to the effect of probiotics on autistic children and adults, preferably with large, randomised and double-blind clinical trials. Professor Gibson has expressed a desire to undertake a larger study in the future with fewer drop-outs.

Autism & diet

Some people believe that the symptoms of autism can be controlled in part by dietary changes, hence a fair amount of those on the autistic spectrum cut out certain foods which are thought to be difficult to digest. In particular many children and adults with autism take on a gluten & casein free diet (known by many as the GF/CF diet). There is not a huge amount of clinical research on the GF/CF diet, and drawbacks could potentially include a decrease in certain useful white blood cells¹⁰ as well as difficulty in reintroducing foods containing elements of gluten or casein. However, some anecdotal evidence suggests that the GF/CF diet could not only help improve digestive health, but also to improve attention & concentration, communication and language, and social integration, amongst other behavioural changes. Other foods which people cut out or reduce include MSG and aspartame flavour-enhancing ingredients, lutein, feingold and complex carbohydrates, starches and processed sugars.

Once again, large and reliable clinical trials into the effects of diet on those on the autistic spectrum would be warmly welcomed and must be called for. It is always best for individuals to see a dietitian or nutritionist before eliminating certain foods in one's diet. In the meantime, anecdotal evidence that diet can alter the symptoms of autism provides further promise for the link between autism and gut health.

References

1. Molloy CA. et al (2003). Prevalence of chronic gastrointestinal symptoms in children with autism and autistic spectrum disorders. Autism. 7:165-171.
2. Finegold. SM. et al (2002) Gastrointesintal microflora studies in late-onset autism. Clinical Infectious Diseases 35: S6-516.
3. Parracho H. et al (2005) Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. Journal of Medical Microbiology 54: 987 - 991.
4. Song, Yuli. et al (2004) Real-Time PCR Quantitation of Clostridia in Feces of Autistic Children. Appl Enciron Microbiol 70(11): 6459-6465.
5.  Williams, BL, Hornig M, Parekh T, Lipkin WI. (2012) Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances. mBio 3(1):e00261-11. doi:10.1128/mBio.00261-11
6. http://www.foodsmatter.com/nutrition_micronutrition/pre_and_probiotics/articles/probiotics_and_autism.html
7. The Gut Microbiota and Autism Spectrum Disorders. Qinrui Li, Ying Han*, Angel Belle C. Dy and Randi J. Hagerman. Front. Cell. Neurosci., 28 April 2017. https://doi.org/10.3389/fncel.2017.00120
8. Single species of gut bacteria can reverse autism-related social behaviour in mice. Baylor College of MedicineBaylor College of Medicine NewsNeuroscienceSingle species of gut bacteria can reverse autism-related social behavior in mice.
9. Mudd (2017) Serum cortisol mediates the relationship between fecal Ruminococcus and brain N-acetylaspartate in the young pig. Gut Microbes. 13:1-12. doi: 10.1080/19490976.2017.1353849.
10. Ashwood P. et al (2003). Intestinal lymphoctye populations in children with regressive autism: evidence for extensive mucosal immunopathology. Journal of Clinical Immunology 23: 504-517.
11. Fadelli I, (2022) New evidence hints at the role of gut microbiota in autistic spectrum disorder. Medical Xpress, https://medicalxpress.com/news/2022-07-evidence-hints-role-gut-microbiota.html
12. Ying-Chieh Tsai, (2022) Neurologically Active Probiotics for Autism. Autism Parenting Magazine, https://www.autismparentingmagazine.com/autism-neurologically-active-probiotics/
13. Azari H, Morovati A, Gargari B, Sarbakhsh P. (2022) An Updated Systematic Review and Meta-Analysis on the Effects of Probiotics, Prebiotics and Synbiotics in Autism Spectrum Disorder. Rev J Autism Dev Disord, https://doi.org/10.1007/s40489-022-00348-0
14. Morton J T et al., (2023) Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles. Nature Neuroscience, 26: 1208-1217.

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