Introduction
There are more than 100 trillion microbial species on the skin, respiratory tract, genital tract and most of the microbiota living in the gut. Nowadays, scientists have conducted several studies showing that mental health is closely related to the brain-gut axis. People with autism spectrum disorder have specific gastrointestinal symptoms. Autism spectrum disorder is one of the mental disorders that pathogenesis may link to the brain-gut axis. Although the cause-effect relationship between ASD and the brain-gut axis is not yet well established, re-establishing gut homeostasis and promoting gut health may be a promising therapy.
Proposed Mechanism of Brain-gut Axis and Autism
Numerous animal studies and human studies show that there is a close connection between ASD and gut microbiota. Although not yet fully understood, it is suggested that gut microbiota communicates with the CNS through several metabolites such as Short Chain Fatty Acids (SCFA), notably butyrate and propionate.
Short Chain Fatty Acids (SCFA)
SCFAs can regulate the production of neurotransmitters such as serotonin and dopamine by entering the brain through the blood-brain barrier. Additionally, SCFA plays a role in immune action by regulating T-cell cytokine secretion. Studies show that the total amount of SCFA is lower in ASD patients compared to neurotypical subjects. There is a significant decrease in butyrate levels, whereas propionate is higher than in neurotypical subjects.
Butyrate
It is a major SCFA and has anti-inflammatory properties in the gut, brain and neuroprotective functions. Even though the role of Butyrate has yet to be furecognisedized, researchers suggest there may be a correlation between butyrate reduction and the pathophysiology of ASD.
Propionate
Propionate is another common SCFA produced by certain bacteria in the gut. Adequate levels of Propionate are known to have protective effects on the body, notably cholesterol-lowering and anti-inflammatory properties; however, some studies observed that excessive Propionate in the bloodstream is associated with behavioural symptoms similar to Autism. Elevated Propionate levels may also degrade the nervous system by acting as a neurotoxin. Moreover, the Clostridium bacteria closely correlated with the severity of ASD mentioned in the previous section is also involved in propionate production.
Other metabolites such as Lipopolysaccharides and P-cresol produced by bacteria have also been observed to contribute to the worsening of ASD symptoms.
Microbiota Dysbiosis
GI (Gastrointestinal) Disturbance is significantly more common in children with ASD when compared to normal individuals of similar age groups. Various studies have also reported an association between GI disturbances and the behavioural phenotype of ASD. Besides social skill deficits, aggressive behaviour and frequent anger outbursts have been reported more frequently in children with ASD with GI disturbances.
Firmicutes, Bacteroidetes, Clostridium
Numerous studies have observed the presence of dysbiosis in ASD. Typical findings include a significant increase in Firmicutes to Bacteroidetes ratio (While not always, but often due to decreased Bacteroidetes) and Clostridium levels (a common bacteria that causes intestinal inflammation), of which conditions are not present in neurotypical children and control subjects. At the same time, the level of Clostridium is also positively correlated with the severity of ASD.
Bfidobacterium, Lactobacillus
Probiotics strains such as Bifidobacterium and Lactobacillus have been studied in neurological and psychiatric disorders, and the results are promising. Some probiotics demonstrated effects of improving anxiety, stress-related GI symptoms, and psychological distress, as well as improvement of some biomarkers within the brain such as glutamate, N-acetyl aspartate and GABA.
Some Promising Therapy Using Theory of Brain-Gut Axis
Probiotic Supplementation
Probiotics are the “good” bacteria in the gut microbiota that play a role in maintaining gut health and modulating the immune system. In recent years, probiotic supplements have been gaining popularity worldwide and can be found in almost every health store or pharmacy.
In the case of ASD, a few human studies suggest probiotic supplementation may improve ASD symptoms. One case study showed improvements after taking an 8-strain probiotic combination for three months as measured by the “Autistic Diagnostic Observation Schedule” the effects lasted up to 9-months after discontinuation of supplementation. Another study showed improvements after a 4-week probiotic supplement and “Applied Behaviour Analysis” training.
Fecal Microbiota Transplant
Faecal Microbiota Transplant (FMT – a procedure for transferring faecal bacteria and other microbes from a healthy donor to another) is being actively studied as a new treatment for many gut microbiota-related diseases well. FMT can alter the diversity of gut microbiota through the transplantation of faeces; this procedure is most often used for treating recurrent Clostridium difficle infection. A study involving 18 ASD children in 2017 demonstrated the therapeutic effect of FMT in ASD children. Improvements in terms of autism symptoms, gastrointestinal disturbances and gut microbiota diversity were observed after the treatment. In 2019, the same team of researchers did a follow-up study on the same subjects. Symptom improvements appear to last as long as two years after the treatment.
Conclusion
The quality of the results of the studies mentioned above was limited by their study design and the number of participants. The efficacy of probiotic treatment requires more large-scale, long-term, and well-designed studies for further validation. Although it is too early to conclude the effectiveness of probiotic therapy, realising the association between gut microbiota and ASD symptoms is a big step towards ASD treatment.