Table 4.
Summary of main findings.
| First Author, Year of Publication, Country | Participants Included in the Study Based on Serum Zonulin and Plasma Haptoglobin | Main Study Findings | Authors Conclusions |
|---|---|---|---|
| Özyurt et al., 2018, Turkey [5] | 81 | Children with ADHD had significantly elevated levels of zonulin compared to controls. Children with hyperactive/impulsive presentations had significantly elevated zonulin compared to other presentations. ADHD symptoms and social communication problems correlated significantly with zonulin levels, and hyperactive/impulsive and social communication symptoms were important predictors of zonulin levels. | “Regardless of its limitations, the results of our study suggest that zonulin levels may be elevated in children with ADHD (especially the hyperactive/impulsive presentation) and that this elevation correlated with social deficits. Symptoms of hyperactivity/impulsivity and social deficits independently predict zonulin levels in children with ADHD although the changes in adjusted R2 suggest that the majority of the predictive value lies with symptoms of hyperactivity/impulsivity.” |
| Esnafoglu et al., 2017, Turkey [6] | 65 | There was an increase in serum zonulin levels in the group with ASD compared with the healthy control group. Additionally, for all subjects, there was a positive correlation identified between the CARS score, indicating severity of autism, and zonulin. | “Increased zonulin levels in patients with ASD may play a role in the development of ASD symptoms. However, zonulin upregulation and subsequent increase in intestinal permeability may be necessary but not sufficient to develop ASD, because other factors are likely at play.” |
| Józefczuk et al., 2017, Poland [7] | 121 | Concentrations of zonulin were the highest in the youngest children (5 years). The mean level of zonulin in this group was significantly higher compared with patients aged 6–11 years. The occurrence of anti-TG6 antibodies in ASD patients with normal mucosa was not associated with CD. | “There is a subgroup of ASD patients whichrespond to gluten with increased production of antibodies against native gluten and neural TG6, but not of typical celiac-specific antibodies, and this production is not related to serological markers of an impaired intestinal barrier.” |
| Rose et al., 2018, California [8] | 87 | Children with ASD who experience GI symptoms have an imbalance in their immune response, possibly influenced by or influencing metagenomic changes, and may have a propensity to impaired gut barrier function, which may contribute to their symptoms and clinical outcome. | “We found several differences when comparing children with ASD who exhibit GI symptoms vs. those that did not. The most notable of these was the reduced regulatory TGFb1 response of the ASDGI groups following stimulation. We also noted an increase in the production of cytokines linked to mucosal inflammation after TLR-4 stimulation in children with ASDGI symptoms relative to children with ASDNoGI. Our analysis of the microbiome underscores the relationship between the presence of GI symptoms and the host microflora and suggest a possible role of dysbiosis in the co-morbidity of GI issues in ASD” |
| Işık et al., 2020, Turkey [9] | 48 | There was an increase in serum claudin-5 levels in the group with OCD compared with the healthy control group. There was no significant difference between the study and control group in the serum zonulin concentrations. | “Regardless of the limitations, taken together with our results, dysregulation of the BBB, especially claudin-5, may be involved in the etiology of OCD. Further detailed and more comprehensive studies designed on a longitudinal basis are greatly needed to find out exactly whether increased claudin- 5 levels are the cause or consequence of the disease process in OCD” |
ADHD: attention deficit hyperactivity disorder. CARS: childhood autism rating scale. ASD: autism spectrum disorders.TG6: transglutaminase 6. IgA: immunoglobulin A. IgG: immunoglobulin G. CD: celiac disease. GI: gastrointestinal. OCD: obsessive–compulsive disorder. BBB: blood–brain barrier.