What is Autism?
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that affects communication, behavior, and social interaction and is often associated with repetitive and restrictive behaviors. ASD continues to perplex researchers and medical professionals worldwide due to its complex nature and the fact that it is increasingly becoming a serious public health problem, with an incidence rate of about 1 in 100 children (WHO, 2023). While the exact etiopathogenesis remain elusive, researchers have been exploring various factors that might contribute to its development. One intriguing area of investigation is the role of the gut microbiome — the vast community of microorganisms residing in our digestive tract on autism through what is known as the gut-brain connection.
Gut Microbiota and Autism
The gut microbiota plays key role in regulating the immune system and prevention of infection by restricting the passage of pathogenic microbial groups from the gut into the bloodstream. An alteration in its composition (dysbiosis) has been implicated in the pathogenesis of various diseases including neuroimmune and neurobehavioral disorders such as ASD. Although the exact cause of ASD is not clearly understood, a growing body of research has examined the potential relationship between the gut microbiome and autism. Majority of ASD patients experience a variety of gastrointestinal dysfunction in addition to abdominal pain and altered bowel habits. These dysfunctions have been suggested to be as a result of an underlying inflammatory process resulting from dysbiosis. Also, the gastrointestinal symptoms experienced by ASD patients has been to be associated with the disease severity. Research has shown a connection between the gut microbiota and the brain in ASD patients.
The gut-brain connection, also known as the gut-brain axis, refers to the bidirectional communication system between the gastrointestinal tract and the brain. The gut microbiome plays a crucial role in this relationship by producing various chemicals and metabolites that can influence brain function and behavior. This connection is established through neural, hormonal, and immune pathways and disruption of these metabolic, neural and inflammatory pathways involved in the central nervous system crosstalk have been shown to be important contributors to the pathogenesis of ASD. These mechanisms can be summarised as; the metabolite influence, neurotransmitter production, and immune system crosstalk (inflammation hypothesis).
Firstly, the gut microbiome produces various metabolites and co-metabolites that can cross the gut-blood and the blood-brain barrier and affect brain function and overall behavior when they enter the bloodstream. Some of these metabolites may impact neural development and behavior, potentially influencing autism. Thankfully, advances in metabolomics have made it much easier to identify and characterise these metabolites. For instance, studies have shown that children with ASD have higher p-cresol, p-cresyl sulfate, propionic acid, and acetic acid. Early exposure to P-cresol has been shown to increase cognitive impairment and disease severity in autism and have been suggested to be involved in the pathogenesis of ASD.
Secondly, gut microbes are capable of producing neurotransmitters such as serotonin and dopamine, which play vital roles in mood regulation, and imbalances in these neurotransmitters are linked to autism. Studies have found an association between the secretion of serotonin and ASD. Specifically, serotonin has been shown to serve as a link between the gut and the brain in ASD. As far back as 1970, a link between Hyperserotonemia (increased whole blood serotonin) and ASD has been established in children. This over-secretion of serotonin is attributed to gastrointestinal hypersecretion and correlated with gastrointestinal symptoms seen in ASD as well as altered microbiota composition. Animal studies have shown that altering the gut microbiome can lead to changes in social behavior, anxiety-like behavior, and communication patterns — all of which are relevant to autism and linked to neurotransmitters production.
Autism and Inflammation
Finally, some research groups have focused on the potential role of inflammation on the gut microbiome and autism. The inflammation hypothesis in ASD originated from the evidence that autistic children have a variety of gastrointestinal disturbances not limited to diarrhoea, constipation, vomiting, feeding problems, reflux, and abdominal pain. There is increasing evidence that the gastrointestinal disturbances observed in ASD is due to dysbiosis resulting from inflammation. Moreover, some studies have found higher levels of inflammatory markers such as fecal calprotectin, lactoferrin, and secretory IgA in individuals with ASD.
Recent scientific investigations have unveiled stronger links between the gut microbiome and autism. According to Prof. Knight from the University of California, “Before these recent investigations, we had smoke indicating the microbiome was involved in autism, and now we have fire. Previously, studies have shown that the microbiota of autistic patients is dominated by Clostridium and Ruminococcus. More recently, using a Bayesian differential ranking algorithm, Morton et al., 2023, identified molecular and taxonomic profiles associated with ASD using 10 cross-sectional microbiome datasets and 15 other datasets. Their results provide a clearer depiction of the microbiota profile in autistic patients.
In summary, the exploration of the link between the gut microbiome and autism is shedding light on the enigma of ASD. The gut-brain axis presents a fascinating avenue of study that holds the promise of uncovering new insights into autism’s origins and progression. As our understanding deepens, researchers may eventually develop innovative interventions that harness the power of the gut microbiome, offering hope for improved outcomes for individuals on the autism spectrum.