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Autism, actually

Explained | How does the gut microbiome link to autism spectrum disorders?

February 20, 2023 10:44 pm | Updated February 28, 2023 04:32 pm IST

An artist’s conception of the gut microbiome.

An artist’s conception of the gut microbiome. | Photo Credit: 3D illustration

‘Fix your gut, fix your brain’ used to be an underrated idea, but it is today gaining in relevance as more and more research throws light on the role of the community of bacteria living in your gut, a.k.a. the gut microbiome.

A healthy gut microbiome is not a panacea – but it may be able to facilitate better overall health and help improve the quality of life of individuals with various diseases that lack other proven interventions. Differences in gut microbiome composition have been implicated in several diseases, including autism, Crohn’s disease, and celiac disease.

What is autism?

‘Autism spectrum disorder’ (ASD) is the term for a group of neurodevelopmental disorders. Researchers are yet to fully understand the aetiology of ASD. (Aetiology is the study of the factors that cause a condition or disease.) However, they are beginning to find that a disorder in the gut-brain axis could have a prominent part.

According to the World Health Organisation, ASD affects one in 100 children. Children with ASD have impaired social interactions, lack verbal and nonverbal communication skills, and display restricted and repetitive behaviours. These characteristics can adversely affect one’s cognitive abilities and, over time, diminish one’s quality of life.

A relatively under-researched aspect of ASD is the gastrointestinal problems associated with a subset of children with ASD. Limited research findings as well as anecdotal evidence indicate, strongly in some cases, the presence of various gastrointestinal problems, like constipation, diarrhoea, flatulence, and bloating, among others, in children with ASD.

But even as researchers have proposed several theories over the years to explain the aetiology of ASD, the pathophysiology of the disorder remains largely unknown. (Pathophysiology is the study of a condition’s impact on biological processes.)

At present, there are no known cures and therapeutic interventions available to treat or reverse ASD.

The forgotten organ


Sudowoodo/ | Photo Credit: Irina Mir

Scientists reached a major milestone in the pursuit to understand human biology when they completed the Human Genome Project in April 2003. But they soon realised that decoding the human genome wouldn’t suffice because of the trillions of microorganisms that live in and on the human body throughout the life cycle, affecting all aspects of life

An offshoot of this realisation was the Human Microbiome Project, conceived in 2007 as a “second human genome project”, this time including the genes of the microbes in the microbiome as well.

The human microbiome, sometimes called the “forgotten organ”, plays a significant role in an array of host processes, including growth, development, physiology, immunity, nutrition, and disease.

Today, researchers’ increasingly profound exploration of the human microbiome, aided by advances in gene-sequencing technologies and high-end bioinformatic analysis, is dramatically reshaping our understanding of the connections between human health, diseases, and microbiomes.

The science of the link

The gut microbiome is believed to have a big impact on immune modulation and metabolic activities in the human body. Immune modulation refers, among other things, to the efforts of the immune system to ensure its response is proportionate to a threat.

Investigations of the dynamic cross-talk between the gut microbiome and the host environment have revealed potential connections to ASD symptoms. For example, aberrant antigen trafficking through an impaired intestinal barrier could allow these antigens to eventually pass through the barrier surrounding the brain, triggering a chain of events that worsen ASD symptoms.

Some scientists have disputed the significance of the gut microbiome by contending that the microbiome can’t cause ASD and therefore its role in the pathophysiology of ASD is limited.

But research on this topic has shown that even if the gut microbiome doesn’t play a causative role, abnormalities in it can challenge a person with toxic metabolites and keep the person from synthesising the metabolites required to produce neurotransmitters involved in cognition, behaviour, mood, and sleep. As a result, ‘fixing’ the gut in ASD can reduce the toxic burden – including that which moves through the blood-brain barrier – and/or help complete the necessary neurotransmitter synthesis pathways.

In our own research (published here, here, and here), we have explored the gut microbiome in children with and without ASD, and have reported several interesting microbial biomarkers in children with ASD. We observed dysbiosis – an imbalance – in the gut microbiome of children with ASD: they had a higher abundance of Lactobacillaceae, Bifidobacteriaceae, and Veillonellaceae bacteria. We also found the fraction of bacteria of the phylum Firmicutes to be significantly higher in the guts of children with ASD. Researchers have consistently linked a higher representation of Firmicutes relative to Bacteroidetes to intestinal dysbiosis.

We also found an underrepresentation of certain microbes that produce short-chain fatty acids (SCFA), such as Faecalibacterium and Roseburia, in children with ASD. This supports the hypothesis that a lower level of SCFAs in ASD could lead to an imbalance in brain function and behaviour. This is the source of proposals to introduce these strains of bacteria as a probiotic for children with ASD, to help alleviate common gastrointestinal problems and in turn positively influence cognitive and behavioural functions.

However, note that these are emerging areas of study: there are pockets of agreement as well as disagreement in the community, and consensus lies in the future.

What can you do?

A 3D illustration of rod-shaped bacteria and cocci from the human microbiome.

A 3D illustration of rod-shaped bacteria and cocci from the human microbiome. | Photo Credit: Dr_Microbe, Getty Images/iStockphoto

Reinstating a balance in the gut microbiome and reversing gut dysbiosis among children with ASD could alleviate many problems they face and improve their quality of life.

One promising approach to reverse gut dysbiosis is faecal microbial transplantation (FMT), where stool samples from healthy individuals are transplanted into the large intestines of affected children.

A small study conducted by Ohio State University in 2017 reported that FMT improved both gastrointestinal and ASD-related symptoms. Since FMT is a cost-effective strategy with low risk, we need to build consensus among all stakeholders – including parents, clinicians, and educators – and create incentives to adopt it.

There is also some evidence that gluten-free and casein-free diets can help children with ASD. This could be because some of these children have been found to lack the bacteria that helps break down casein and gluten into metabolites.

In all, the role of diet, prebiotics, probiotics, synbiotics (which combine the benefits of probiotics and prebiotics), and FMT for the efficient management of ASD can be said to be encouraging.

A comparative metagenome/microbiome analysis of the gut of children with ASD using next-generation sequencing costs about Rs 25,000. A physician could use the consequent report to identify which essential bacteria are deficient in a child, and prescribe prebiotics to supplement the nutrients supplied by these bacteria. Medical researchers may also be able to develop bespoke probiotics with specific bacterial strains; these are called next-generation probiotics.

No part of this article should be construed as medical advice. Please act only in consultation with your physician.

Tony Grace is assistant professor, Department of Genomic Science, Central University of Kerala, and adjunct assistant professor, Division of Biology, Kansas State University. Joby Pulikkan is postdoctoral research associate, University of Virginia.

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