We analyze how bacterial composition could influence the development of the autism spectrum and its impact on childhood health

The microbiota and its metabolites play a fundamental role in maintaining health and balancing the immune system, as well as in the production of vitamins and the metabolization of nutrients.

In the previous article we observed the importance of the microbiome-gut-immune system-brain axis and how communication errors between these systems could negatively impact gastrointestinal and/or mental health. The authors of the study, which we talked about in the previous article, came to the conclusion that in cases of autism spectrum disorder (ASD) it was necessary to study and address both mental health and gastrointestinal health, seeing a possible new therapeutic avenue in modulation of the intestinal microbiota. 

Are there differences in the composition of the microbiota between children with autism spectrum disorder (ASD) and neurotypical children?

We know that the intestinal microbiome is unique in each individual and that it is composed of an infinite number of microorganisms (bacteria, parasites, viruses and archaea) and their metabolites, but we also know that it is modulable.

Microbial variability and, consequently, its metabolites, can be affected by many factors, including genetics, age, sex, cultural habits, diet, lifestyle, medications and exposure to pathogens, among others. . Then by working on some of these factors we can make important changes in the intestinal microbiome.

The metabolites produced by the intestinal microbiota have different effects on human health and well-being. Some of the most important metabolites are:

1. Short chain fatty acids (SCFAs): acetate, propionate and butyrate, are products of bacterial fermentation of non-digestible carbohydrates in the colon, with beneficial effects on the body (they serve as a source of energy for intestinal epithelial cells, maintain the integrity of the intestinal barrier, regulate inflammation and exert anti-inflammatory and antitumor effects).
2. Amino acids and vitamins: Some intestinal bacteria can synthesize amino acids and vitamins that we do not produce or that we cannot obtain in sufficient quantities through diet alone. 
3. Bioactive metabolites: neurotransmitters that affect mood and behavior, such as gamma-aminobutyric acid (GABA) and serotonin; others related to lipid and carbohydrate metabolism, which affect weight and energy metabolism; and some that regulate inflammation and the immune system.
4. Fermentation products: gases (carbon dioxide, hydrogen and methane), volatile compounds (acetic acid and lactic acid), with different effects on intestinal health and gastrointestinal comfort.

In summary, gut bacteria produce a wide range of metabolites that can influence health and well-being. These metabolites participate in maintaining the integrity of the intestinal barrier, in regulating the immune system and in energy metabolism. Knowing and understanding the functioning of these bacterial metabolisms and how they affect will be necessary to understand the relationship between the intestinal microbiota and human health.

Can a characteristic microbial pattern be identified in children with autism spectrum disorder (ASD) using advanced DNA sequencing and bacterial metabolite analysis?

There are microbial patterns that depend on certain variables and some of these can be associated with known disorders and diseases (gastrointestinal disorders, metabolic diseases, autoimmune disorders and neuropsychiatric disorders). At this point, it is logical to ask whether there is a specific microbial pattern for autism spectrum disorders (ASD).

To find out if there really is a generalized difference between the microbiome of ASD children and that of neurotypical children, countless studies have been carried out. Some have focused on the observation and comparison of the microbiota in children with neurodevelopmental disorders and neurotypical children using advanced DNA sequencing techniques to analyze the microbial composition and diversity in stool samples, others have focused on the study of the metabolites produced by that microbiota and some included samples of the maternal microbiota. The sequencing techniques used made it possible to identify and quantify the microorganisms present in the intestine with a high degree of precision.

In some of these studies, standardized questionnaires were added to evaluate participants' gastrointestinal and neurological symptoms.

As an example, let's look at the results obtained in some of these studies:

1. Study by Finegold and collaborators (2010): They found significant differences between both microbiotas, observed an increase in the proportion of clostridial bacteria and a decrease in the abundance of bifidobacteria in ASD children compared to neurotypical children.
2. Study by Williams and collaborators (2011): This study examined the gut microbiota of children with ASD and neurotypical children using DNA sequencing techniques and found differences in the diversity and composition of the microbiota, with lower microbial diversity in children with ASD.
3. Study by Tomova and collaborators (2015): This study examined the gut microbiota in children with ASD and neurotypical children, as well as the microbiotas of their mothers. They found differences in microbiota composition between children with ASD and neurotypical children, and an association between the microbiota composition of children and their mothers.
4. Study by Strati and collaborators (2017): The composition of the intestinal microbiota in children with ASD and typical children was analyzed by DNA sequencing and found significant differences in the abundance of certain bacterial species, as well as an association between the severity of ASD symptoms and the composition of the microbiota.

In a more current review, December 2023, by the Division of Molecular Microbiology, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, called: 'The Role of Short-Chain Fatty Acids and Altered Microbiota Composition in Autism Spectrum Disorder: A Comprehensive Literature Review', a total of 22 studies were analyzed (including those mentioned above), the first from 2004 and the last from 2023 and with all this it could not be concluded that there was an exact characteristic profile in patients with ASD, however, they were found certain patterns.

The explanation for these results could be attributed to the diversity of the patients, since ASD has a fairly wide range of symptoms, comorbidities and factors that participate in its development, both genetic and environmental; that the sample sizes were small; and that the variability of the microbiome depends on many other factors, such as geographical origin, different diets, age, lifestyle or even the use of antibiotics, among many others.

• Differences in bacterial composition: Specific changes were observed among children with ASD, with an altered proportion of certain phyla, increased Bacteroidetes and decreased Firmicutes. Some genres were also reduced, for example, Bifidobacterium, Firmicutes, Prevotella or Streptococcus and yet others were increased, such as Clostridium, Bacteroides, Ruminococcus or Desulfovibrio. The Bacteroids are related to the production of propionate and the Desulfovibrio with the production of propionate, lipopolysaccharides (LPS) and hydrogen sulfide, all of them with the possibility of producing toxic effects.

• Decrease in microbial diversity: Lower microbial diversity (less variety of species) in children with ASD, which could be associated with a decrease in microbiome resilience, this could influence a gut that is more susceptible to pathogen colonization or microbiota imbalances, which could play a role. of ASD symptoms.
• Factors that influence the microbiota in ASD: Possible factors that contribute to an altered microbiota in children with ASD, such as diet, antibiotic use, environmental exposure to toxins and genetics. Stress and anxiety, common in people with ASD, could also influence the composition and function of the intestinal microbiota.
• Relationship between microbiota and ASD symptoms: It seems that associations could be found between the presence of certain bacterial species associated with the severity of gastrointestinal symptoms, behavioral problems or communication difficulties in individuals with ASD.
• Other possible mechanisms: Intestinal inflammation, production of microbial metabolites, immune function, and microbiota-brain communication could also influence the development and expression of ASD symptoms. It has been observed that the levels of some metabolites produced by certain bacteria in the microbiota tend to be dysfunctionally increased in individuals with ASD, in particular propionic acid. This excess could be related to both gastrointestinal and neurological symptoms.

Conclusion

All these findings suggest that there is an association between the composition of the intestinal microbiota and its metabolites with the development and expression of ASD and that in addition the composition of the microbiota of ASD children differs from that of neurotypical children.

A regulation of the microbiome could contribute to the improvement of ASD symptoms. Research in this field needs many more studies to fully understand the relationship between the gut microbiome, ASD and its clinical relevance.

Article written by Enevia Health Collaborator: Loles Marco 

Graduated in Human Nutrition and Dietetics.

lolesmarcobermudo@gmail.com

Bibliography:

1. Lagod, Piotr P, and Saleh A Naser. “The Role of Short-Chain Fatty Acids and Altered Microbiota Composition in Autism Spectrum Disorder: A Comprehensive Literature Review.” International journal of molecular sciences vol. 24, 17432. 13 Dec. 2023, doi: 10.3390/ijms242417432
2. del Campo-Moreno, Rosa, et al. "Microbiota in human health: characterization and transfer techniques." Infectious diseases and clinical microbiology 36.4 241-245, 2018, doi: 10.1016/j.eimc.2017.02.007

To learn more about this topic, we leave you the link to the previous article and our Web

The Influence of the microbiome and intestinal mucosa health in ASD