Vitamin A deficiency increases the risk of gastrointestinal comorbidity and exacerbates core symptoms in children with autism spectrum disorder

Cheng, Boli; Zhu, Jiang; Yang, Ting; Guo, Min; Lai, Xi; Li, Qiu; Chen, Jie; Li, Tingyu

doi:10.1038/s41390-020-0865-y

Cited by 26 publications

(14 citation statements)

References 36 publications

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“…This is interesting, in part, because we know little about mechanisms controlling radial migration of ENS precursors to the submucosal plexus, with prior studies implicating only GDNF and netrin/DCC signaling in this process ( 50 , 51 ). These observations highlight the remarkable range of ENS abnormalities that may occur when RAR signaling is inadequate and are consistent with the observation that low serum vitamin A is associated with increased constipation in children with autism ( 52 ).…”

Section: Discussionsupporting

confidence: 88%

Cell-autonomous retinoic acid receptor signaling has stage-specific effects on mouse enteric nervous system

et al. 2021

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Retinoic acid (RA) signaling is essential for enteric nervous system (ENS) development since vitamin A deficiency or mutations in RA signaling profoundly reduce bowel colonization by ENS precursors. These RA effects could occur because of RA activity within the ENS lineage or via RA activity in other cell types. To define cell-autonomous roles for retinoid signaling within the ENS lineage at distinct developmental time points, we activated a potent floxed dominantnegative RA receptor α (RarαDN) in the ENS using diverse CRE recombinase-expressing mouse lines. This strategy enabled us to block RA signaling at pre-migratory, migratory, and postmigratory stages for ENS precursors. We found that cell-autonomous loss of retinoic acid receptor (RAR) signaling dramatically affects ENS development. CRE activation of RarαDN expression at pre-migratory or migratory stages caused severe intestinal aganglionosis, but at later stages, RarαDN induced a broad range of phenotypes including hypoganglionosis, submucosal plexus loss, and abnormal neural differentiation. RNA-sequencing highlighted distinct RA-regulated gene sets at different developmental stages. These studies show complicated context-dependent RAmediated regulation of ENS development.

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Section: Discussionsupporting

confidence: 88%

Cell-autonomous retinoic acid receptor signaling has stage-specific effects on mouse enteric nervous system

et al. 2021

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“…Some studies demonstrated that the deficiency of retinol in rats during pregnancy decreases RA receptor expression (RAR, beta isoform) in the hypothalamus, causing autistic-like symptoms in the neonates [135]. Interestingly, a lower level of retinol was detected in some autistic subjects when compared with the normal control group in China, which was possibly a synergistic factor in ASD symptom development [136]. Retinol supplements can activate RAR expression and lessen ASD symptoms.…”

Section: Retinoic Acid (Ra) Signaling Pathwaymentioning

confidence: 99%

Dysregulation of Multiple Signaling Neurodevelopmental Pathways during Embryogenesis: A Possible Cause of Autism Spectrum Disorder

Upadhyay

Patra

Tiwari

et al. 2021

Cells

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Understanding the autistic brain and the involvement of genetic, non-genetic, and numerous signaling pathways in the etiology and pathophysiology of autism spectrum disorder (ASD) is complex, as is evident from various studies. Apart from multiple developmental disorders of the brain, autistic subjects show a few characteristics like impairment in social communications related to repetitive, restricted, or stereotypical behavior, which suggests alterations in neuronal circuits caused by defects in various signaling pathways during embryogenesis. Most of the research studies on ASD subjects and genetic models revealed the involvement of mutated genes with alterations of numerous signaling pathways like Wnt, hedgehog, and Retinoic Acid (RA). Despite significant improvement in understanding the pathogenesis and etiology of ASD, there is an increasing awareness related to it as well as a need for more in-depth research because no effective therapy has been developed to address ASD symptoms. Therefore, identifying better therapeutic interventions like “novel drugs for ASD” and biomarkers for early detection and disease condition determination are required. This review article investigated various etiological factors as well as the signaling mechanisms and their alterations to understand ASD pathophysiology. It summarizes the mechanism of signaling pathways, their significance, and implications for ASD.

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“…Nevertheless, there is no substantial evidence to support the efficacy of vitamin and mineral supplementations in improving children with ASD symptoms [42]. A recent study investigated the effect of Vitamin A deficiency on children with ASD and concluded Vitamin A deficiency exacerbates the core symptoms in children with ASD, especially when there are comorbid GI symptoms [43]. Vitamin C may have an effect on children with ASD, based on its vital role in brain neurons development, functional maturation, and antioxidant effect [44].…”

Section: Role Of Vitamins and Minerals In Asdmentioning

confidence: 99%

A Review of the Efficacy of the Dietary Intervention in Autism Spectrum Disorder

Taha

Abdalhai

2021

Open Access Maced J Med Sci

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BACKGROUND: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with 1 in 68 children prevalence. The key symptoms of ASD include social deficits, verbal and non-verbal communication deficits, and restricted, repetitive patterns of behavior, interests, or activities. For unknown reasons, gastrointestinal symptoms are related to ASD. The aim of the current paper is to review the available literature on dietary interventions in children with ASD and provide up-to-date evidence. METHODS: Searches in online databases, using the search terms’ dietary intervention, “autism spectrum disorders,” and “autism” were conducted. The search targeted publications ranging from 2010 to 2020. RESULTS: Twenty-six studies with different study designs which evaluated the effectiveness of specific dietary interventions in children with ASD were included in our review. Several dietary interventions were of popular practice in the management of children with ASD, including elimination (gluten-/casein-free diet and oligoantigenic diet), modification (modified ketogenic diet), supplementation (minerals, vitamins, omega 3, and omega 6), and exclusion (food additives). Studies showed different results with varying degrees of evidence. Overall, data were inadequate to make accurate conclusions. CONCLUSION: There is little evidence to support the use of dietary interventions for children with ASD. Additional high-quality studies and further research are, therefore, needed.

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Vitamin A deficiency increases the risk of gastrointestinal comorbidity and exacerbates core symptoms in children with autism spectrum disorder

Cited by 26 publications

References 36 publications

Cell-autonomous retinoic acid receptor signaling has stage-specific effects on mouse enteric nervous system

Cell-autonomous retinoic acid receptor signaling has stage-specific effects on mouse enteric nervous system

Dysregulation of Multiple Signaling Neurodevelopmental Pathways during Embryogenesis: A Possible Cause of Autism Spectrum Disorder

A Review of the Efficacy of the Dietary Intervention in Autism Spectrum Disorder

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