Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges

Table 7 The different biotic interventions to modulate the gut-brain axis

Intervention type	Definition/source	Key mechanisms on gut-brain axis	Examples	Observed effects (general and specific)
Probiotics	Live microorganisms (e.g., bacteria or yeast) that, when administered in adequate amounts, confer a health benefit on the host	Directly modulate the gut microbial composition. They produce short-chain fatty acids like butyrate, which can cross the blood-brain barrier. They also modulate the production of neurotransmitters (e.g., gamma-aminobutyric acid, serotonin) and reduce systemic inflammation	Bacteria: Lactobacillus species (Lactobacillus rhamnosus, Lactobacillus acidophilus), Bifidobacterium species (Bifidobacterium longum, Bifidobacterium infantis)	General: Improved mood, reduced anxiety, improved gut health (e.g., reduced IBS symptoms). Specific: Probiotics with Fructo-oligosaccharide in children with autism spectrum disorder were found to improve autism-related symptoms, increase beneficial bacteria, and reduce the hyper-serotonergic state and dopamine metabolism disorder
Prebiotics	Selectively fermented ingredients (often non-digestible fibers) that nourish and result in specific changes in the composition and/or activity of the beneficial gastrointestinal microbiota	Indirectly influences the brain by serving as food for beneficial gut bacteria, thereby increasing short-chain fatty acid production (especially butyrate). They enhance gut barrier function and indirectly influence the nervous system by reducing inflammation and modulating short-chain fatty acid signaling	Fibers: Fructans (inulin, Fructo-oligosaccharides), Galacto-oligosaccharides	General: Selective growth of beneficial bacteria (Bifidobacteria, Lactobacillus), enhanced mineral absorption, reduced constipation. Specific: Fructo-oligosaccharide used in combination with probiotics in children with autism spectrum disorder was associated with improved symptoms and beneficial gut change
Synbiotics	A product containing both Probiotics (live microorganisms) and Prebiotics (their selectively utilized food substrate) in a combined form	Combines the direct seeding and modulating effects of probiotics with the selective nourishment and short-chain fatty acid-boosting effects of prebiotics, potentially offering a synergistic effect on the gut-brain axis	Commercial blends containing strains such as Bifidobacterium and a fiber source such as Fructo-oligosaccharides or inulin	Effects are similar to or enhanced versions of those observed with single-agent interventions, often formulated to maximize the survival and activity of the probiotic strain

This table provides a clear taxonomy of interventions targeting the microbiota-gut-brain axis, a critical communication pathway between the central nervous system and the gut. These interventions aim to correct microbial dysbiosis, which is hypothesized to contribute to neurodevelopmental conditions like autism spectrum disorder. Probiotics are live microbial supplements that directly modulate the gut's composition and function, producing crucial metabolites like short-chain fatty acids (e.g., butyrate) that can influence the brain and modulate neurotransmitter systems (e.g., serotonin). Prebiotics are non-digestible fibers that indirectly support brain health by selectively feeding beneficial bacteria, thereby boosting short-chain fatty acid production and enhancing the intestinal barrier. Synbiotics combine both components to produce a synergistic effect potentially. In the context of autism spectrum disorder, specific studies on the combination of probiotics and fructo-oligosaccharides have shown promise, not only improving gut health but also reducing autism-related symptoms and correcting key metabolic issues, such as reducing the hyper-serotonergic state and dopamine metabolism disorder. This highlights a targeted strategy to manage autism spectrum disorder-associated symptoms and comorbidities by leveraging the connection between the gut and the brain. IBS: Irritable bowel syndrome.