Autism. Axa microbiota-intestin-creier

Autism. The microbiota-gut-brain axis

In recent years, there has been a significant increase in studies related to disorders in the autistic spectrum that are related to intestinal and microbiota changes. Many people with ASD have digestive disorders, and their severity correlates with the degree of ASD impairment.

Gut-microbiota-brain axis

The gut-brain axis, or better said, the microbiota-gut-brain axis, involves a complex communication between the gut, the microbiota and the central nervous system. This communication is achieved through the production by the intestinal microbiota of substances such as neurotransmitters, cytokines, short chain fatty acids (SCFA) and other metabolites.

Also, activation the vagus nerve communicate bidirectional between gut and brain. Likewise, activation of the sympathetic nervous system and the HPA axis (cortisol) sends signals from the brain to the gut and microbiota. The intestinal microbiota therefore has a fundamental role in these communication pathways.

Intestinal microbiota produce neurotransmitters such as norepinephrine, dopamine, glutamate, serotonin or GABA.

In addition, changes in brain function can be produced by mechanisms dependent on subzero inflammation that occurs in the context of dysbiosis or changes in the homeostasis of the immune system due to the signaling it receives from the gut microbiota.

What are autism spectrum disorders (ASD)?

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with impaired social interaction and communication, usually along with repetitive and restrictive behaviors. The prevalence of TsA is progressively increasing, reaching figures of 1 in 43 children in the US or 1 in 28 in South Korea.

A person's development of ASD has been linked to genetic factors – with up to 400 genes or genomic regions involved – and environmental factors such as nutritional deficiencies or excesses, exposure to viruses, immune system disorders and allergies.

Microbiota and autism spectrum disorders.

In addition, studies linking ASD to gut and microbiota changes have increased in recent years. Many people with autism spectrum disorders have digestive disorders, and their degree of severity correlates with the degree of impairment in terms of ASD.

There are several studies that indicate that children with ASD have changes in the composition of their microbiota, leading to the disorder the barrier of the intestinal mucosa . This, in turn, can facilitate the passage of exogenous substances of food or bacterial origin (such as bacterial lipopolysaccharide -LPS-) into the blood, thus causing the production of pro-inflammatory cytokines.

It is known that breastfeeding for more than 6 months can increase the risk of ASD due to the programming of the immune system and its beneficial effects on the microbiota. Even the mother's diet during pregnancy can influence the microbiota of the newborn. In studies that have been conducted both in animal models of ASD and in children with ASD, it has been found that the microbiota is different in the presence of ASD.

Dysbiosis and autism spectrum disorder

In children with ASD, there is often a loss and diversity of microbiota with an overgrowth of harmful bacteria. It has been seen that in people with ASD there is usually a decrease in Firmicutes with a relative increase of Bacteroidetes, which by manufacturing short chain fatty acids - SCFA, in particular propionate, can influence behavior by modulating the brain axis.

Low levels of Bifidobacterium, Prevotella, Coprococcus and Veillonellaceae, which are responsible for the digestion and fermentation of carbohydrates. Instead, there will be an increase in lactobacilli, Clostridium, Desulfovibrio and Enterobacteria, among others.

Antibiotic resistant bacteria

More exactly, Desulfovibrio, a bacteria resistant to antibiotics such as cephalosporins, is quite common in children with ASD. These children tend to have more ear infections than neurotypical children and often receive many antibiotics. This favors emergence dysbiosis and overgrowth of this bacteria.

Regarding Clostridium, one study found that children treated with vancomycin against Clostridium difficile improved their digestive and neurobehavioral symptoms.

Certain strains of Clostridium PRODUCTION toxic metabolites AS phenols, p-cresol and indoles , so their excess has a global effect on digestive system and brain. It also appears that the deleterious role of glyphosate on neurodevelopment may be partially mediated by increased growth of toxigenic Clostridia.

Likewise, the mushroom Candida albicans appears to be up to twice as abundant in children with ASD compared to neurotypical children, which can lead to the production of ammonia and other toxins.

Metabolomics studies

On the other hand, in metabolomic studies performed in children with ASD, it was observed that there is an excess of toxic metabolites such as the aforementioned p-cresol and its metabolite p-cresyl sulfate, in addition to a relative deficiency of butyrate compared to acetate and propionate.

All are microbial metabolites and an intestinal dysbiosis causes metabolomic changes with direct effect on intestinal function and axis gut-brain.

There is really no single clear profile of dysbiosis that is universal for all people with ASD; because it depends a lot on factors such as age, diet, drugs, place of residence... and there is great heterogeneity between the different published studies in terms of the characteristics of the groups studied.

Hyperserotoninemia, another additional factor

Another additional factor that seems to be able to influence people with autism spectrum disorders is hyperseroninemia, which has already been shown in the over 70s to influence digestive symptoms. Serotonin production is strongly influenced by the microbiota. 90% of serotonin is produced in the gut microbiota.

However, due to inflammation below zero, there would be a deficit of serotonin in the brain due to the interference of its production by pro-inflammatory cytokines. Even so, the role of serotonin in the symptoms of people with ASD is still not very clear, although evidence suggests that the microbiota also plays a key role.

Food and probiotics, key tools in TS A

In order to improve intestinal dysbiosis that can aggravate neurobehavioral changes or digestive symptoms in people with ASD, nutrition is essential. An anti-inflammatory and prebiotic diet, avoiding ultra-processed dysbiotic foods, is very convenient.

There are already studies supporting the exorphin theory, with the changes improving with gliadin and casein withdrawal, although more studies would be needed, ideally in a multimodal intervention approach. Of course, it is convenient to rule out celiac disease in anyone with neurobehavioral and digestive symptoms, including children with ASD, before switching to an exclusion diet.

The ketogenic diet also appears to be helpful in some cases, although it is probably not necessary in most cases and, if considered, should be under the supervision of a health professional.

Probiotics in autism spectrum disorders

It has been postulated that because antibiotics can reduce intestinal inflammation and improve gastrointestinal symptoms, they may be helpful in people with ASD. There are already quite a few animal studies that have achieved positive results. In fact, the intervention would be ideal if it were already carried out during pregnancy, assessing even previously the state of the maternal oral and intestinal microbiota.

Currently, there are preliminary results in humans with some strains of Lactobacillus acidophilus, Lactobacillus rhamnosus, and Bifidobacteria longum. There are also some studies with commercial mixtures of lactobacilli and bifidobacteria.

In most of the studies done, maybe the problem is because the strategy is not individualized/customized, the dysbiosis profile is not the same in all people, so the probiotic integration strategy should also be different from person to person. For a complete and complex evaluation there is the test for analyzing the entire digestive system MAX profile . This extensive study provides a lot of information and following the results we can create a personalized treatment strategy.

On the other hand, starting to give certain strains of bifidobacteria and lactobacilli without first implementing a strategy to eliminate or reduce excess harmful microbes may be another factor causing suboptimal results in some studies.

In the future, prevention and treatment will include an increasing presence of microbiomics and metabolomics in any neurodegenerative disease, such as Parkinson's, or in neurodevelopmental disorders, such as autism.

There is hope that new lines of research will open up in these areas of study to seek the benefit of affected individuals.

Bibliography; Dr. Sari Arponen –

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