Vitamin D and Autism Spectrum Disorder

1,25(OH)2D is the hormonally active form of vitamin D known for its pleiotropic immunomodulatory effects. Via altering gene transcription, 1,25(OH)D exerts immunosuppressive effects and stimulates immune regulation. Recently, the interest in vitamin D in association with autism spectrum disorder (ASD) has been triggered. The prevalence of ASD has increased excessively over the last few decades, emphasizing the need for a better understanding of the etiology of the disorder as well as to find better treatments. Vitamin D levels in ASD patients are observed to be lower compared to healthy individuals and maternal vitamin D deficiency has been associated with an increased risk of ASD. Moreover, vitamin D supplementation improves ASD symptoms. These recent clinical findings strongly suggest that vitamin D is a factor in ASD onset and progression. Yet, possible mechanisms behind this association remain unknown. This review summarizes immunomodulatory properties of vitamin D and peripheral immune dysregulation in ASD, after which possible mechanisms via which vitamin D could rebalance the immune system in ASD are discussed. Although promising clinical results have been found, further research is necessary to draw conclusions about the effect and mechanisms behind the effect of vitamin D on ASD development

Distribution of Month of Birth of Individuals with Autism Spectrum Disorder Differs from the General Population in the Netherlands

The prevalence of autism spectrum disorders (ASDs) is causally dependent on genetic and environmental influences. We investigated whether autism spectrum disorders are associated with month of birth compared to the general population using a retrospective study, comparing ASD cases (n = 3478) with the general population (n = 2,716,876) born between 1995 and 2008. Associations were examined using χ2 tests and Walter and Elwood’s seasonality χ2 tests for the total ASD group, and separately for autistic disorder and Asperger syndrome. For the total ASD group, the distribution of month of birth was different compared to the general population (p < 0.0001), with July as the highest contributor, and a season-of-birth effect was found for this group (p = 0.02). For the autistic disorder group, the months of birth distribution were different (p = 0.01), with July as the highest contributor. No season-of-birth effect over the year was found (p = 0.09). No association was found for the months of birth of individuals with Asperger syndrome (p = 0.06), with no seasonal trend over the year (p = 0.60). In conclusion, a drop in sun exposure during the first trimester of pregnancy might explain the peak in July births and the associated risk for ASD development

Hypoallergenic infant formula and methods for preparing the same

The invention relates to the field of infant nutritional formulations, in particular to methods for providing a hypoallergenic nutritional composition based on cow's milk protein for infants who are at risk of developing cow's milk allergy (CMA). The method comprises the steps of: (i) providing a partial hydrolysate of the milk protein(s), obtained by subjecting a starting composition comprising one or more bovine milk protein(s) in an aqueous medium to an enzymatic treatment, (ii) clearing the partial hydrolysate from one or more components capable of RAGE- binding and/or having a basophil degranulation inducing capacity; (iii) optionally concentrating the cleared partial hydrolysate; and (iv) formulating the (concentrated) cleared partial hydrolysate into a nutritional composition for infants who are at risk of developing CMA

Hypoallergenic infant formula and methods for preparing the same

The invention relates to the field of infant nutritional formulations, in particular to methods for providing a hypoallergenic nutritional composition based on cow's milk protein for infants who are at risk of developing cow's milk allergy (CMA). The method comprises the steps of: (i) providing a partial hydrolysate of the milk protein(s), obtained by subjecting a starting composition comprising one or more bovine milk protein(s) in an aqueous medium to an enzymatic treatment, (ii) clearing the partial hydrolysate from one or more components capable of RAGE- binding and/or having a basophil degranulation inducing capacity; (iii) optionally concentrating the cleared partial hydrolysate; and (iv) formulating the (concentrated) cleared partial hydrolysate into a nutritional composition for infants who are at risk of developing CMA

Vitamin D receptor gene polymorphisms associated with childhood autism

Background: Autism spectrum disorder (ASD) is a group of heterogeneous, behaviorally defined disorders whereby currently no biological markers are common to all affected individuals. A deregulated immune response may be contributing to the etiology of ASD. The active metabolite of vitamin D3has an immunoregulatory role mediated by binding to the vitamin D receptor (VDR) in monocyte, macrophages, and lymphocytes. The effects of vitamin D and interaction with the VDR may be influenced by polymorphism in the VDR gene. Methods: Genetic association of four different VDR polymorphisms (Apa-I, Bsm-I, Taq-I, Fok-I) associated with susceptibility to the development of autism in children was investigated. Results: We uniquely found an association between the presence of the T allele at position Taq-I and presence of the a allele at position Apa-I of the VDR gene with decreased ASD incidence. There was also an association between female gender and the presence of the T allele. We found no statistical significant correlation between VDR single nucleotide polymorphisms (SNPs) and vitamin D3concentration in serum of ASD children. Conclusion: Genetic polymorphism in two SNP in VDR may be correlated with development of ASD symptoms by influencing functionality of vitamin D3metabolism, while vitamin D3levels were not significantly different between ASD and non-ASD children

Toll-Like Receptor-dependent immunomodulatory activity of Pycnogenol

Background: Pycnogenol® (PYC), a patented herbal extract of French maritime pine bark, consists of a complex mixture of bioflavonoids. The main constituents of PYC are procyanidins; biopolymers consisting of units of catechin (CAT) and epicatechin. PYC is shown to exert immunomodulatory properties, nevertheless its underlying mechanisms are not yet fully elucidated. Methods: In this study, the effect of PYC and its constituent CAT on membrane Toll like receptor (TLR) activity was examined using stably transfected Human Embryonic Kidney cells. The Human monocytic leukaemia cell line THP-1 was used to examine the effect of PYC and CAT on pro-inflammatory cytokine release.Findings: We showed that non-metabolised PYC acts as agonist of TLR1/2, TLR2/6 and a partial agonist of TLR5, which resulted in the induction of pro-inflammatory cytokine secretion from THP-1 macrophages as well as activation of Nf-κB transcription factor. This effect was altered due to gastrointestinal metabolism, which revealed immuno-suppressive potential against TLR 1/2 and TLR 2/6 of the retentate fraction compared to the control sample. Moreover, the dialysed fraction did not show potential to induce pro-inflammatory cytokine secretion by THP-1 macrophages but the capacity to induce anti-inflammatory IL-10. Moreover, we showed that PYC on its own does not activate TLR4 but the formation of complexes with lipopolysaccharides (LPS) is required to stimulate the TLR4 receptor. We found that PYC and PYC-LPS complexes to the same extend dose-dependently increase pro-inflammatory cytokine levels (IL-8, IL-1β and TNF) and upregulate phosphorylation of the transcription factor NF-ĸB. No effects for CAT were observed on TLR activation and pro-inflammatory cytokine production levels. Conclusions: Our study stresses the importance of metabolism for biological activity of PYC compounds. Moreover our results suggest that bot non-metabolised as well as metabolised PYC acts via TLR 1/2 and TLR 2/6 next to TLR4

The influence of breast milk and infant formulae hydrolysates on bacterial adhesion and Caco-2 cells functioning

The aim of the study was to determine the concentration of BCM7 in human milk and infant formulae (IF) before and after eznymatic hydrolysis, and to evaluate the effect of obtained hydrolysates on interleukin-8 (IL-8) secretion and on proliferation of enterocytes in the in vitro model (Caco-2 cells). This study evaluates also the effect of hydrolysates on the adhesion of intestinal microbiota isolated from faeces of both healthy (H) and allergic (A) infants. In the study we investigated breast milk delivered by mothers of healthy (‘healthy milk’ HM) and allergic (‘allergic milk’ AM) infants. Three infant formulae were investigated: from hydrolysed cow casein (IF1), from hydrolysed cow whey (IF2) and from whole cow milk (IF3). Intestinal bacteria: Bifidobacterium, lactic acid bacteria, Enterobacteriaceae, Clostridium and Enterococcus were isolated from faeces of five healthy and five allergic infants. Mixtures of bacterial isolates and bacteria adhering to Caco-2 cells were characterised qualitatively with PCR-DGGE, and quantitavely with FISH. Concentration of BCM7 in breast milk and infant formulae was 1.6 to 8.9 times higher after enzymatic hydrolysis in comparison to undigested samples. The presence of this peptide resulted in alteration of intestinal epithelial proliferation and increase in secretion of IL-8. The quantitative profile of adherred bacteria applied as a mix of all isolates from healthy infants (H-MIX) was unchanged in the presence of HM hydrolysate and was modulated (increased number of beneficial Bifidobacterium and reduced commensal Enterobacteriaceae) in the presence of all IF hydrolysates. The presence of IF hydrolysates affected the profile of adhering isolates obtained from allergic infants (A-MIX) and reduced the adhesion of Enterobacteriaceae; the IF2 and IF3 hydrolysates decreased also the total number of adhering bacteria (TBN). However, a stimulating effect of AM hydrolysate on A-MIX adhesion (increased TBN) was observed.</p

An alternative inhibition method for determining cross-reactive allergens

Inhibition assays are an useful tool to identify the allergen of primary sensitization of cross-reactive allergens. Classical ELISA-based inhibition assays are limited by both the availability of commercial standardized allergen extracts and the experience and knowledge needed for making home-made extracts. Moreover the direct comparison of the inhibition ELISAs outcomes between different laboratories is difficult because of different sources of used allergen extracts and a number of methodological variations. Therefore, we propose a novel ImmunoCap (Phadia, Thermofisher Scientific) based immunoinhibition method with the use of commercially available Caps as the allergen source. The novel ImmunoCap based immunoinhibition method was developed and tested with sera from patients with a well-known cross-reactive sensitization for fig (Ficus carica) and ficus (Ficus benjamina). Results were compared with a classically applied inhibition method, i.e. addition of homemade allergen extract to patient serum. The amount of allergens (fig and ficus extracts) needed to reach a similar degree of inhibition was comparable for both inhibition methods. The ImmunoCap based inhibition assay, in addition to classical inhibition methods, is a valuable tool as the ImmunoCap analyzer and commercial allergens (Caps) are more widely available which makes the outcomes of inhibition tests comparable between different laboratories. Furthermore, in the ImmunoCap inhibition method the same protein source is used for both the inhibition of sIgE and sIgE measurement, which might be even more relevant when multiple cross-reactive allergens are tested