Discovery of a new link between autism and gut microbiota

A strong weight of evidence supports the hypothesis of a link between gut dysbiosis and autism. For example, many ASD patients suffer from gut imbalances–such as a deficiency of Bifidobacterium longum and an excess of Clostridium spp. and Candida albicans–, which are thought to be associated with inflammation of the gut and increased permeability of the gut-blood barrier. In addition, gastrointestinal comorbidity and digestive enzyme deficiencies are more common in children with ASD. Despite this, the mechanisms involved and the contribution of the gut microbiota to the development of ASD remain poorly understood.

A novel pairing strategy

However, a decisive step forward may now have been taken. In a study published in Science Advances, a research team compared the gut microbiota of 39 children with ASD to that of 40 neurotypical children of the same age and gender. This first analysis revealed differences in 18 bacterial species between these two groups but could not explain the exact role of the gut microbiota in the development of the disease. To control for interindividual diversity of the microbiota, the researchers developed a strategy consisting of pairing each ASD patient to a control subject based on the metabolic profile of their microbiota. A novel cohort of 65 pairs was thus created, with a metagenomic analysis performed to identify the metabolic pathways that differed between the two groups.

Impaired intestinal microbial detoxification

Among the 96 metabolic pathways associated with ASD, five that are involved in intestinal detoxification were significantly deficient compared to the control subjects, as were 8 enzymes involved in the degradation of toxins contained in insecticides and food additives. The authors believe that these detoxification impairments in ASD children may contribute to mitochondrial dysfunction, which can affect all tissues, including brain tissue. Based on these data, the researchers constructed a diagnostic model capable of discriminating ASD children from control subjects with 88% accuracy.

Increased gut permeability

This finding may explain why children with ASD are so vulnerable to environmental toxins and suggests that the impaired gut detoxification process in ASD patients may be involved in the development of the disease. However, the reasons for deficiencies in microbial detoxification remain unclear. One hypothesis points to a gut dysbiosis which, by causing increased intestinal permeability, allows environmental toxins to enter the bloodstream. Among other effects, these toxins may alter the mitochondria in the brain. If confirmed, this hypothesis could pave the way for new therapeutic strategies aimed at restoring the microbial detoxification capabilities of ASD patients, according to the authors.