A new identifiable marker in the functional and multikingdom intestinal microbiota for ASD. ¿What is its relationship with dysbiosis?

The gut microbiota is composed of trillions of microorganisms residing in the human gastrointestinal tract, playing crucial roles in digestion, immunity, and metabolic health. This complex and dynamic ecosystem has become an area of great scientific and clinical interest, as more is discovered about its implications for health and disease, based on research into its composition, functions, factors affecting its balance, and its relationship to various health conditions.

The gut microbiota is made up of a wide variety of microorganisms, including bacteria, viruses, fungi, and protozoa. The diversity of these populations is crucial to maintaining a healthy balance in the gut. Bacteria are divided into multiple phyla, with the most predominant being Firmicutes and Bacteroidetes.

Other significant phyla include Actinobacteria, Proteobacteria, and Verrucomicrobia. Microbial composition can vary considerably between individuals, influenced by factors such as genetics, diet, age, environment, and lifestyle habits. Assessment of the gut microbiota is often performed through DNA sequencing techniques, which allow the identification of the diversity and abundance of microbial species present in the gut.

Functions of the Intestinal Microbiota

The intestinal microbiota performs multiple functions essential for human health, which can be categorized into several areas:

• Digestion and Metabolism

One of the most fundamental roles of the gut microbiota is the digestion of food components that the human system cannot process on its own. For example, dietary fibers are fermented by certain bacteria, producing short-chain fatty acids (SCFAs) such as butyrate, acetate, and propionate, which are important for gut and metabolic health; these are important metabolic products generated by the fermentation of dietary fibers by gut bacteria. These compounds play a crucial role in gut health and overall metabolism.

Butyrate is the main fuel for colon cells and has anti-inflammatory properties. Its production is linked to a healthy microbiota. In conditions of dysbiosis, butyrate production may be decreased, which may contribute to intestinal disorders such as colitis. 

Acetate is the most abundant SCFA in the intestine and is used as an energy source by various tissues, as well as being a precursor for lipid synthesis. In cases of dysbiosis, the increase in certain microorganisms can promote excessive acetate production, which could be related to obesity and insulin resistance.

Propionate is also associated with regulating lipid metabolism and improving insulin sensitivity. Dysbiosis can alter propionate production, negatively affecting sugar regulation and fat metabolism.

They also participate in the regulation of energy storage, nutrient extraction and the production of metabolites that impact various metabolic pathways. Interactions between the microbiome and the host are vital to maintain energy balance and glycemic homeostasis.

For example, a diverse and balanced microbiome is associated with improved insulin sensitivity and a lower predisposition to obesity and metabolic diseases. Microbiome imbalance, known as dysbiosis, has been linked to conditions such as type 2 diabetes, inflammatory bowel diseases, and obesity.

• Regulation of the Immune System

The gut microbiota is a key modulator of the immune system. It interacts with immune cells in the gut, helping to develop and maintain tolerance to harmless antigens, such as foods, and to respond effectively to pathogens. This relationship is vital, as dysbiosis (disturbance of microbial balance) can contribute to autoimmune and inflammatory diseases.

From the first moments of life, the microbiome begins to influence the development of the immune system through its interaction with immune cells residing in the gut. This immunological education is crucial to establishing a balance between an adequate immune response against pathogens and a tolerance to non-harmful antigens, such as foods and beneficial bacteria that also inhabit the gut.

Metabolic products generated by the microbiome, such as short-chain fatty acids (SCFAs), play a crucial role in this regulation. For example, butyrate, a SCFA produced from the fermentation of dietary fibers, not only acts as an energy source for colon epithelial cells but also has anti-inflammatory properties.

Butyrate acts on immune cell receptors, promoting the production of anti-inflammatory cytokines and decreasing inflammation. This is especially relevant in the context of inflammatory bowel diseases, where a healthy microbiome can help mitigate symptoms and promote remission.

In addition, the gut microbiome contributes to the intestinal barrier, a crucial defense that regulates gut permeability. A balanced microbiome helps maintain the integrity of this barrier, preventing the translocation of pathogens and toxins into the bloodstream. Dysbiosis, on the other hand, can weaken this barrier, which can trigger inappropriate immune responses and contribute to the onset of autoimmune diseases and allergies.

The microbiome also influences the production and activity of immunoglobulins, especially immunoglobulin A (IgA). IgA is essential for mucosal defense, as it is secreted in the gut and helps neutralize pathogens and toxins. Microbial diversity in the gut is associated with increased IgA production, which strengthens the gut's ability to resist infections.

Furthermore, the microbiome affects the systemic immune response by influencing the maturation and activity of regulatory T cells and effective T cells. Regulatory T cells play a crucial role in preventing autoimmune reactions and maintaining immune tolerance. A healthy microbiome promotes the expansion of these cells, helping to prevent autoimmune diseases and allergies.

On the other hand, dysbiosis can lead to hyperactivation of the immune system, promoting chronic inflammation, which is associated with various pathologies, including metabolic disorders, gastrointestinal disorders and neurodegenerative diseases. The relationship between the microbiome and the immune system is an area of intense research and therapies that modulate the microbiome, such as probiotics and prebiotics, are being explored to restore a healthy balance and improve immune health.

• Production of Essential Nutrients

In addition to fiber fermentation, the intestinal microbiota is responsible for the synthesis of certain vitamins and nutrients. For example, some species of bacteria can synthesize B vitamins and vitamin K, which are essential for various metabolic functions.

• Protection against Pathogens

The gut microbiota protects against pathogens through several mechanisms. It competes for resources and space, produces antimicrobial substances, and modulates local immune responses. This protective effect is crucial for preventing infections and maintaining a healthy gut.

Some factors can influence alterations in the intestinal microbiota, such as diet, which is one of the most important determinants of the intestinal microbiota. Diets rich in fiber, fruits, vegetables and fermented foods tend to favor microbial diversity, while diets poor in these elements can lead to a decrease in diversity and dysbiosis.

Antibiotics are known to dramatically alter the gut flora, eliminating not only pathogenic bacteria, but also many of the beneficial bacteria. This can lead to an increase in the colonization of opportunistic pathogens, such as Clostridium difficile, which can cause serious infections.

The composition of the intestinal microbiota varies throughout life. In newborns, the microbiota begins to be colonized during birth, and its composition remains changeable as the individual grows. As we age, the diversity of the microbiota tends to decrease, which may be associated with an increase in health problems.

Factors such as physical activity, stress and sleep habits can also influence the gut microbiota. An active lifestyle and good stress management are associated with greater microbial diversity, while a sedentary lifestyle and chronic stress can promote a less healthy microbial profile.

The relationship between gut microbiota and health is complex and multidimensional. Several studies have found associations between dysbiosis and a variety of health conditions.

• Metabolic Diseases

The gut microbiota has been shown to play a crucial role in glucose and lipid metabolism. Imbalances in microbial composition have been linked to obesity, insulin resistance, and type 2 diabetes. For example, obese individuals tend to have lower microbial diversity compared to their lean counterparts.

• Inflammatory Bowel Diseases

Diseases such as Crohn's disease and ulcerative colitis are associated with significant alterations in the gut microbiota. Certain microbes have been observed to be more abundant or scarce in patients with these conditions, suggesting that modulating the microbiota may be a viable therapeutic target.

• Mental Health

Communication between the gut microbiota and the central nervous system, known as the gut-brain axis, has been the subject of intense research. There is evidence to suggest that the microbiota may influence mood and behavior through the production of metabolites and neurotransmitters.

• Cardiovascular Diseases

The relationship between gut microbiota and cardiovascular disease has also been investigated. Some studies suggest that certain bacterial species may influence lipid metabolism and promote inflammation, contributing to atherosclerosis.

Promoting a healthy gut microbiota is the key to regulating all of these functions mentioned above and we can do this through a balanced diet with foods such as fiber, fruits, vegetables, and fermented foods (such as yogurt, kefir, and sauerkraut) can help promote a diverse and balanced gut microbiota.

Reducing unnecessary use of antibiotics is crucial to preserve microbial diversity. Whenever possible, non-antibiotic approaches should be used to treat infections and prevent multi-drug resistance in pathogenic bacterial populations.

Regular physical activity not only benefits overall health, but can also support the diversity of the gut microbiota. Stress management through techniques such as meditation, yoga or mindfulness can have positive effects on the composition of the microbiota. Adequate sleep is also essential for maintaining a healthy microbial balance.

The gut microbiota is an essential component of human health, influencing digestion, metabolism, the immune system and more, understanding its complexity and the way it interacts with our bodies is critical to addressing many of the major health concerns of the modern world.

Promoting a healthy gut microbiota through a balanced diet, an active lifestyle and proper stress management can significantly contribute to improving health and preventing disease.

As research in this field continues to advance, it is likely that new microbiota-based therapies and strategies will be developed in the future, opening the door to innovative treatments for a variety of health conditions.

A recent study from the Chinese University of Hong Kong has comprehensively analyzed the intestinal microbiome of more than 1,627 children between the ages of 1 and 13 years with and without ASD. The study of samples from appropriate populations and controls can provide us with results that improve our understanding of the relationship between the microbiome and autism spectrum disorder and offer biomarkers for the diagnosis of this disorder.

Using metagenomics to investigate autism, metagenomic sequencing is an advanced technique that allows the identification and characterization of all microorganisms present in a sample from their hereditary material, whether bacteria, archaea, fungi or viruses. The researchers used this strategy to analyze fetal samples from these children, with autism spectrum disorder or neurotypical, from five cohorts in China.

In this way, they accurately identified and quantified the different microbial species present, as well as their genes and metabolic pathways, across the range of neurodiversity marked by the different children. In addition, to ensure that the results were accurate and not biased by other variables, the team considered additional factors such as diet, age, medication and comorbidity. 

The results revealed significant alterations in the microbiome of children with autism spectrum disorder compared to neurotypical children. Specifically, 14 species of archaea, 51 species of bacteria, 7 species of fungi, 18 viruses, 27 microbial genes, and 12 metabolic pathways were found to show differences in abundance between neurotypical children and children with autism spectrum disorder. A decrease in the diversity of these microbial populations was also observed in children with autism spectrum disorder, as well as a general decrease in the abundance of many species, most pronounced in bacterial communities. 

The team of researchers also found two reduced biosynthetic pathways in children with autism spectrum disorder compared to neurotypical children: those corresponding to ubiquinol-7 and thiamine diphosphate, two metabolites important for mental health. This is of relevance because ubiquinol has been shown to improve symptoms in children with autism spectrum disorder and impaired synthesis of thiamine diphosphate has been associated with autism spectrum disorder and other mental disorders in both animal and human studies. 

Furthermore, a negative association was detected between autism spectrum disorder and a regulatory pathway of 4-aminobutyric acid (GABA), an essential neurotransmitter of the central nervous system of mammals, also related to autism spectrum disorder in previous studies. The main limitation of the data obtained is that a cause-effect correlation between the alteration of the microbiome and autism could not be established. That is, a causal role for these observed alterations in the development of the disorder could not be assessed.

The results of the study have several potential applications. First, the model of 31 identified microbial markers could be used in the future to develop more accurate and noninvasive diagnostic tests for autism spectrum disorder. 

Using machine learning techniques, the researchers developed a model based on the 31 microbial and functional markers, with potential for the diagnosis of autism spectrum disorder. So far, this model showed greater diagnostic accuracy in identifying autism spectrum disorder compared to previous models that considered only one microbial kingdom (such as bacteria or archaea). In addition, it showed consistent results across the five groups of children analyzed. 

Furthermore, based on the altered biological pathways identified, the researchers also propose possible therapeutic development strategies. The study suggests that the biosynthesis pathways of ubiquinol-7 and thiamine diphosphate, which are less abundant in children with autism spectrum disorder, could become new therapeutic targets for targeted treatments based on microbiome modulation.

The exciting thing about this study is that it opens up the possibility of investigating specific biochemical pathways and their impact on different autistic traits. It could also offer new ways to detect autism, if microbial markers strengthen the ability of genetic and behavioral tests to detect autism. A future platform that can combine genetic, microbial, and simple microbial and behavioral assessments could help to overcome the deficiencies in detection. The researcher also highlights that with the results of this study, the lens through which we view the microbiota within autism has definitely been expanded.

At Enevia we offer specialized consulting services and different tests that can guide you in different areas such as neurology, genetics, nutrition and general medicine, as well as help you make the right decisions and analyze medical tests to achieve effective treatment for the pathologies that you may suffer from.

Enter our website through www.eneviacare.com and www.eneviahealth.com and you will be able to find the services that we can offer you.

At Enevia, we are your ally in health!

We also leave you with some articles that we published on our blog about microbiota and its relationship with Autism that might be of interest to you:

https://test.eneviahealth.com/blog/influencia-de-la-microbioma-en-el-tea/

https://test.eneviahealth.com/blog/microbiota-diferencia-ninos-tea-neurotipicos/

https://test.eneviahealth.com/blog/desequilibrios-microbiota-influencia-en-tea/

Bibliographic References

• Guarner F. Role of intestinal flora in health and disease. Nourish Hosp. 2007 May; 22 (Suppl 2): 14-19. On-line.
• Su, Q., Wong, O.W.H., Lu, W. et al. Multikingdom and functional gut microbiota markers for autism spectrum disorder. Nat Microbiol 9, 2344–2355 (2024). https://doi.org/10.1038/s41564-024-01739-1
• Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci 2005; 23: 183-187.