RESEARCH - Neural Plasticity

Autism Spectrum Disorder (ASD) and GI Disorders

Authors: Guillermo Vela, Peter Stark, Michael Socha, Ann Katrin Sauer, Simone Hagmeyer, Andreas M. Grabrucker

Zinc in Gut-Brain Interaction in Autism and Neurological Disorders

Improving zinc status of a pregnant mother may improve the gut development of the neonate and mitigate dysfunctions associated with ASD, due to the multifaceted effects of elemental zinc on gut development and morphology.

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In this report, the research team investigated the relationship of prenatal zinc status of the mother with neonatal development of associated ASD's.

EDITORS NOTE: The focus of this report is on a single nutrient - zinc. We recommend hTMA for determining metabolic status, toxic burden, directing nutritional therapeutics, and for monitoring progress. And while the importance of zinc is clearly demonstrated in this report, biology requires multiple essential minerals at proper levels and in relationship with each other (ratios) to achieve health in both the mother and child.

A growing amount of research suggests that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases.

For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life.

Prevention and Treatment Strategies

For prenatal prevention, zinc may be effective to overcome the negative effects of dietary constituents and nutrients in prenatal supplements and help women to maintain adequate zinc status. For postnatal therapy, zinc supplementation may be useful in young children with ASD helping to overcome some impairments associated with acute zinc deficiency (diarrhea, impaired immune function, and neurosensory deficits).

Young children with ASD also might benefit from probiotic therapy to correct gut permeability, alter microbial composition, reduce burden of bacterial waste products and metabolites, and thereby ameliorate ASD symptoms. Additionally, a gluten and milk protein-free diet may be beneficial for individuals with ASD. Therapeutics used to treat inflammatory events caused by abnormal GI function (both anti-inflammatory and immune-modulating therapies) might be beneficial.

Stress is linked to abnormalities in the GI tract and mediated by, among others, the corticotropin-releasing factor (CRF) system at the molecular level. The use of CRF receptor antagonists (stress reduction) may provide new effective treatment approaches.

Supplementing women of childbearing age with an effective source of zinc might help mitigate the negative effects of dietary constituents and nutrients in prenatal supplements on zinc availability, helping women attain and maintain adequate zinc status. Although measures to prevent maternal zinc deficiency would be most desired, further treatment strategies emerge from this concept for young children with ASD. For example, the use of probiotics in ASD has been suggested. However, probiotics have been used with variable efficacy and data on the effectiveness of probiotics is currently just emerging with more studies and meta-analyses needed in the future.

Additionally, a gluten and milk protein-free diet was reported to potentially be beneficial to improve some behaviors in individuals with ASD and reduce intestinal permeability. Elimination of cow's milk protein from the diet of ASD children via restrictive diet improved autistic behavior.

In general, the gut microbiome might have great impact on brain development early in life. In an altered microbiome, bacterial metabolites such as 4-ethylphenylsulphate (4EPS) or the neurotransmitter γ-aminobutyric acid (GABA) produced from intestinal bacteria might affect brain development and, ultimately, behavior later in life.

Serotonin (5-HT) signaling is not only important in the brain, but also in the GI tract. The 5-HT(1A) receptor plays an important role in the developing brain but is additionally expressed in the gut. 5-HT is released from gut enterochromaffin cells and might contribute to 5-HT signaling in the brain. However, the gut and the brain are not the only sites of action for 5-HT. Its receptors are also present in the immune system where 5-HT signaling may mediate both innate and adaptive responses. It remains to be established whether 5-HT3 antagonists or 5-HT4 agonists can have a modulatory effect in ASD.

The intestinal tract has a very important immune function. Besides markers for inflammation, enhanced levels of cytokines and chemokines have been detected in the brain and in the cerebrospinal fluid of children with autism. Therefore, therapeutics used to treat inflammatory events caused by abnormal GI function, such as in inflammatory bowel disease, might be a potential source for novel treatment strategies.

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