Some studies suggested a link between the gut microbiota and autism, based on observed differences in gut bacteria, mouse experiments showing behavioral changes after microbiota manipulation, and small human trials using probiotics or fecal transplants. However, the evidence is often inconsistent.

Now, a Perspective article published in Neuron concludes that there is currently no robust evidence of a causal link between the gut microbiota and autism. 

“I don’t think it’s warranted to spend further time and funding on this topic,” says Kevin Mitchell at Trinity College Dublin, who led the work. “We know that autism is a strongly genetic condition, and there’s still loads to be worked out there.”

Mitchell and his colleagues reviewed the scientific literature on autism and the gut microbiota, evaluating study designs, sample sizes, statistical methods, and behavioral assays in mice.

Inconsistent findings

The research examining the role of gut microbiota in autism includes observational studies, experiments in mice, and clinical trials. Observational studies in humans have reported differences in gut microbial composition between autistic and non-autistic people, but findings are inconsistent and often based on small sample sizes. 

Mouse experiments, which aim to model autism-like behaviors and assess microbiota interventions, face challenges related to the validity of behavioral assays and differences between human and mouse gut microbiotas. 

While some studies report behavioral effects following microbiota manipulation, these results are limited by small sample sizes, methodological variability, and limited replication, the authors say.

Methodological concerns 

Clinical trials in humans have mostly been small, open-label studies without control arms, making it difficult to distinguish treatment effects from placebo responses.

Randomized controlled trials, which provide more rigorous evidence, have so far not shown consistent or meaningful effects of microbiota interventions, such as probiotics or fecal microbiota transplants, on autism-related traits. 

Meta-analyses of these trials also reported limited evidence of benefit and noted methodological concerns including small sample sizes and potential biases, including the influence of financial conflicts of interest, the authors say.

Future work

Future studies should have clearly defined hypotheses, adequate sample size, standardized protocols, and replication using multiple independent approaches. This would help ensure that findings are robust and reproducible, the authors say.

Overall, there is no strong evidence that the gut microbiota causally influences autism, they add. Similarly, claims that microbiota interventions can prevent or treat autism should be interpreted with caution.

Although the review focused on autism, the gut microbiota has been linked to many other conditions, including mental health conditions and neurodegenerative diseases, the authors note. “Given that the same methods have been used for most of these studies, it seems likely that they may suffer from the same methodological shortcomings.”