Khaberni - A recent study has shown that the gut microbiome is not related to autism, despite the widespread popularity of this hypothesis in recent years.
A group of scientists argued in an opinion paper published in the journal Neuron that the scientific evidence supporting this hypothesis is weak and unconvincing.
The scientists noted that previous studies, including observational studies, autism mouse models, and human clinical trials, were limited by false assumptions, small sample sizes, and the use of inappropriate statistical methods.
Lead author Kevin Mitchell, a developmental neuroscientist from Trinity College Dublin, says, "I don't think there is justification to allocate more time and funding to this topic. We know that autism is strongly genetic, and there is still much to study."
Why has the gut microbiome hypothesis persisted?
The hypothesis partially arose from the observation that many individuals with autism experience gastrointestinal issues. Additionally, the rising rates of autism diagnoses led some to believe that environmental or behavioral factors might play a role, even though evidence suggests this increase reflects greater awareness and expanded diagnostic criteria, not a biological change.
Nevertheless, scientists continued to study the relationship between the gut microbiome and autism by comparing the microbiome in affected and unaffected individuals, studying mouse models, and conducting human clinical trials. However, the results were often inconsistent and unconvincing, according to Dorothy Bishop, the lead researcher at Oxford University: "There is significant variability in these three types of studies."
Problems in study design
In the most commonly used studies, which compare the microbiomes of individuals with autism and those without, the sample sizes were very small, ranging from 7 to 43 participants per group, while statistical standards recommend using thousands of samples.
Darren Dally, the co-researcher and biostatistician at University College Cork, says, "Autism is not rare, so there is no reason to conduct studies with only 20 or 30 or 40 participants."
Moreover, methods of characterizing the microbiome varied among studies, making comparisons difficult. Although some studies showed differences between the microbiomes of those with and without autism, these results were inconsistent and often vanished when factors such as diet or comparisons between affected children and their neurotypical siblings were considered.
Mitchell adds, "If there is any causal effect, it may be that autism itself affects a person's diet, which in turn could affect their microbiome."
Mouse models and human clinical trials are limited
Studies suggest that mouse models of autism are unconvincing due to behavioral and physiological differences between humans and mice.
Mitchell says, "There is no evidence that 'autism-like' behaviors in mice are related to human autism, and the trials themselves feature methodological and statistical flaws."
Human clinical trials, which involved stool transplants or the administration of probiotics, were often limited in sample size and did not follow random distribution or include a control group.
Dally says, "The consensus in the studies we conducted is that when the trials are conducted properly, no results emerge."
Given the lack of compelling evidence, scientists believe the hypothesis that the microbiome causes autism has reached a dead end.
