Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions

Abstract

Autism spectrum disorder (ASD) is a complex behavioral syndrome that is characterized by speech and language disorders, intellectual impairment, learning and motor dysfunctions. Several genetic and environmental factors are suspected to affect the ASD phenotype including air pollution, exposure to pesticides, maternal infections, inflammatory conditions, dietary factors or consumption of antibiotics during pregnancy. Many children with ASD shows abnormalities in gastrointestinal (GI) physiology, including increased intestinal permeability, overall microbiota alterations, and gut infection. Moreover, they are "picky eaters" and the existence of specific sensory patterns in ASD patients could represent one of the main aspects in hampering feeding. GI disorders are associated with an altered composition of the gut microbiota. Gut microbiome is able to communicate with brain activities through microbiota-derived signaling molecules, immune mediators, gut hormones as well as vagal and spinal afferent neurons. Since the diet induces changes in the intestinal microbiota and in the production of molecules, such as the SCFA, we wanted to investigate the role that nutritional intervention can have on GI microbiota composition and thus on its influence on behavior, GI symptoms and microbiota composition and report which are the beneficial effect on ASD conditions.

Keywords: anthropometry; autism spectrum disorders (ASD); diet; gastrointestinal symptoms; gut microbiome; metabolites; nutritional status.

Figure 1

Factors that could determine food selectivity (data taken from the studies of Williams, Schreck and Klein [52,53,54]).

Figure 2

Synopsis of ASD food selectivity on nutritional status, anthropometric features and clinical conditions.

Figure 3

Role of the gut-brain axis in the etiology of ASD. (1,2) Food that escapes digestion can be used by the gut microbiota bacteria to produce metabolites (e.g., SCFAs and/or 5′-HT) that can be used by the host. Among metabolites (3) 5′-HT is produced particularly by Lactobacillus, Streptococcus, and Lactococcus species, while SCFAs (e.g., propionate) are produced by Clostridia, Bacteroidetes, and Desulfovibrio species. (4) Increased 5′-HT production by the microbiota acts on the metabolism of 5’-HT, leading to tryptophan depletion and contributing to hyperserotonemia, which is associated with GI Symptoms. (5) Intestinal permeability in children with ASD could allow passive diffusion of metabolites, and cause neurodevelopment disorders, such as behavioral and chemical changes (e.g., mood, cognitive state and emotion). (6,7) Moreover, higher intestinal permeability allow the increase in circulating bacteria-derived lipopolysaccharide (LPS), thus stimulating systemic pro-inflammatory cytokines production (e.g., IL-1B, IL-6, IL-8, and IL-12p40), which is associated with impaired social communication. (8) The vagal-mediated signaling from the gut microbiota to the brain can be transmitted through vagal chemoreceptors on mucosal villi that are activated by bacterial metabolites (e.g., 5′-HT, SCFAs) or by vagal mechanoreceptors that sense motility changes induced by bacterial species. (9) Gut microbiota influences the activity of Hypothalamus-Pituitary-Adrenal glands (HPA) axis that increased levels of cortisol in the systemic system. As a consequence, higher levels of cortisol may affect cytokines response and exacerbate GI symptoms.