A mystery called autism: is epigenetics to blame? Or bacteria?

Twenty-five years ago, autism was known only through the movie Rainman, but today it is a relatively common diagnosis that affects the lives of many families. Although we still do not know the exact cause of autism, there has been an increasing amount of research recently that has shed light on some of the mechanisms behind its onset. And with this, the hope is growing that it may eventually be possible to treat it, or at least to alleviate its symptoms.

Autism (or more accurately, autism spectrum disorders, as there are many described) is a developmental mental disorder that manifests itself primarily in impaired social interaction, repetitive behaviour patterns and communication problems. A large proportion of autistic people find it difficult to regulate their behaviour, tend to be reclusive, and in some forms of autism (e.g. Asperger’s syndrome) often create entire imaginary worlds.

Autism is often associated with mental retardation – it used to be reported that up to 75% of cases, but today this estimate is significantly lower, as more and more people are diagnosed with Asperger’s syndrome, whose carriers have normal or even very high intelligence. In the past, these people were often simply labelled as ‘weird’ and only in recent years have they been diagnosed with autism.

Autism usually becomes fully apparent around the child’s third year, but some symptoms can be observed in the first few months of life – these children usually communicate less, do not seek eye contact and prefer things to faces. Boys are more likely to suffer from autism, but if girls are affected, their disability is more severe.

Genetic influences certainly play a role in the development of autism. Identical twins are more than 60% likely to be affected (some studies report up to 90%). However, there is still no evidence that the problem is linked to any particular genetic variation. Therefore, experts are more inclined to believe that it is a combination of certain genetic predispositions with other influences. The high concordance of disabilities in identical twins may then be due to, for example, influences acting during pregnancy.

So what factors, according to recent research, can lead to autism spectrum disorders?

Epigenetics in the lead role

In recent years, with the development of a scientific field called epigenetics, there has been a growing body of research looking for the cause of autism in biochemical reactions that affect the activity of genes in DNA. The brains of autistic people show certain differences from those of healthy people, such as smaller neuron sizes and different densities in different areas. These differences are probably due to defects in neurogenesis (nerve cell formation) and apoptosis (cell death), processes that are largely influenced by epigenetic processes.

A number of differences in epigenetic patterns have already been confirmed. For example, in one autism spectrum disorder, differences in methylation have been found at 55 sites in the genome, and differences in histone acetylation (especially in the histone H3 region) andconcentrations of some microRNAs, which are short chains of ribonucleic acids that carry no genetic information but can completely block the “reading” of many genes in DNA. They even found differences in the levels of microRNAs in the blood, which is very important information. This means that in the future, autism could be diagnosed at an early age just by detecting microRNAs.

Interestingly, some theories link the onset of autism to environmental toxins (such as mercury). In addition to acute poisoning, heavy metals cause a number of negative epigenetic changes.

Essential vitamin D

This vitamin has long been mentioned mainly in connection with bone development and the prevention of osteoporosis, but more and more research is confirming that its importance in the body is much more fundamental, also due to its epigenetic action. Its deficiency is involved in the development of a number of serious diseases. And since vitamin D is also essential for proper brain development, it is not surprising that it may be linked to the development of autism spectrum disorders.

The importance of this nutrient during pregnancy is probably quite crucial. An analysis of the blood of more than three thousand Swedish newborns, for example, showed that those who are vitamin D deficient have a 33% higher risk of suffering from autism. And a Dutch study of more than 4 000 children found that if a woman is vitamin D deficient, her child’s risk of autism more than doubles.

Research has also shown that vitamin D supplementation can reduce the severity of autism symptoms in children.

Are mitochondria to blame for autism?

A number of studies have turned attention to the association of autism with mitochondrial function. Mitochondria are small cellular organelles whose main function is to convert nutrients into energy through oxidation. In children with autism spectrum disorders in particular, dysfunction in the mitochondria has often been observed, particularly in the area of impaired redox metabolism within these organelles. Some studies have reported the occurrence of these disorders in up to 80% of autistic children, but in others the results are significantly lower.

In addition, autism is usually associated with various abnormalities, such as increased oxidative stress, glutathione deficiency or excess TNF-alpha, which can also negatively affect mitochondrial function.

In addition, as in the case of epigenetic reactions, there is also a possible link to the effects of certain environmental toxins. For example, the function of mitochondria can be severely impaired by heavy metals, polychlorinated biphenyls or pesticides, which are also frequently mentioned as possible links to autism.

The underestimated gut microbiome

Many scientists are also turning their attention to the gut microbiome. This term refers to the huge population of microorganisms that inhabit our gut, including bacteria, viruses, yeasts and more – together more than our body’s own cells. In recent years, an increasing number of diseases and disorders have been confirmed to be linked to disruption of the gut microbiome, and autism may be one of them. (Read more about the microbiome here: https://www.epivyziva.cz/tajemny-svet-uvnitr-nasich-strev-bakterie-ovlivnuji-nase-zdravi-i-genetickou-informaci/)

Disruption of the balance of the gut microbiome occurs for a number of reasons. These may be influences during pregnancy and childbirth (the child’s intestines are populated by the mother’s microbiome during pregnancy and childbirth), the influence of nutrition (especially in the absence of breastfeeding), frequent use of antibiotics or excessive hygiene in the first years of life, when the child’s contact with microorganisms promotes the proper development of the microbiome.

Interestingly, some bacteria that are part of the gut microbiome produce substances that subsequently affect mitochondrial function. These are mainly short-chain fatty acids, namely butyrate and propionate.

Propionate in particular can play a big role here. One of the frequently mentioned hypotheses is that when the organism is exposed to an increased concentration of this substance at certain times during development, it leads to deviations in brain development and behaviour that are typical of autism spectrum disorders. This would be suggested by the fact that increased amounts of propionate have been found in the stool of autistic people.

Propionate is produced in the intestines by certain species of bacteria, especially bacteria of the genera Clostridia and Desulfovibrio, which produce it from carbohydrates and amino acids, especially those found in wheat. In this context, it is interesting that some nutritional guidelines recommend a gluten-free (or even dairy-free) diet for children with autism. However, the effectiveness of these measures has not yet been sufficiently scientifically proven.

Is autism infectious?

Increased levels of Clostridia and Desulfovibrio bacteria have been repeatedly confirmed in the gut of people with autism, leading to the suggestion that this disorder may also have an infectious cause. Both types of bacteria have a high level of resistance to antibiotics.

And speaking of antibiotics, some hypotheses link the increased risk of autism to the overuse of antibiotics, which disrupt the balance of the gut microbiota.

Can autism be cured?

Unfortunately, despite all the above information, we still cannot say that we can cure autism. What is hopeful, however, is that virtually all of the above factors can be at least partially reversed. So, it is certainly worthwhile in the case of autistic children (and also in the case of women who are pregnant or about to become pregnant) to control the factors that influence the course of epigenetic reactions in the body and the state of the gut microbiome – to focus on improving the diet, especially in terms of reducing the intake of carbohydrates, saturated fats and food additives and seeking a healthy environment. If possible, it is certainly worthwhile to prefer breastfeeding to artificial nutrition, not overdoing it with hygiene and avoiding overuse of antibiotics.

As for natural substances used as dietary supplements, their effectiveness has not yet been reliably confirmed. Here are some that look promising from the point of view of the studies carried out so far.

Butyrate

It is a substance produced by certain types of gut bacteria that has epigenetic effects and significantly affects mitochondrial function, including that of brain cells. Its administration has been shown to be effective in a number of psychiatric diagnoses, such as depression, as well as in some types of dementia (including Alzheimer’s disease), and even in brain damage due to injury. Initial research on the subject (so far conducted only in animal models) then suggests that it could also be beneficial for people with autism.

Vitamin D3

As mentioned above, a deficiency of this vitamin is likely to play a large role in the development of autism and its administration may also alleviate symptoms. Therefore, supplementation is important not only for children under one year of age (all infants in the Czech Republic receive it on prescription), but also and especially for pregnant women and those who are about to become pregnant. The three in the name of the vitamin means that it is an animal form of vitamin D, which is better for the body to use compared to the plant form D2.

Chlorella

For example, some research describes the positive effects of long-term use of chlorella. This microscopic freshwater algae can effectively remove mercury from the body and also influence the metabolism of sulphur compounds, which is often disturbed in autistic people. Chlorella also protects the hormone glutathione from oxidation by free radicals and also has a protective effect on the intestinal mucosa. However, more research is needed to prove the effectiveness of chlorella in autism.

EGCG

Research on the use of green tea extract, which is a rich source of epigallocatechin gallate, also looks interesting. This substance, for example, was able to eliminate the autistic symptoms induced by valproate in experimental rats.

Omega-3

Although cases have been described where the administration of these unsaturated fatty acids has led to an improvement in autism symptoms, their effectiveness in this regard has not yet been reliably demonstrated. However, it is an absolutely crucial nutrient for brain development, so its use (not only) in autistic children is desirable. Sufficient intake is then quite crucial during pregnancy.