Dataset Information

Evidence of altered salivary cytokine concentrations in Rett syndrome and associations with clinical severity

ABSTRACT:

Background

Immune dysregulation may play a role in the development of Rett syndrome (RTT), a neurodevelopmental disorder caused by mutations of the MECP2 gene. Abnormal cytokine concentrations have been documented in the serum of individuals with RTT. Measurement of salivary cytokines has been investigated as a potential alternative approach to measurement in blood and serum, but it is unclear whether salivary cytokine concentrations can provide valid information about systemic immune function in neurodevelopmental disorders. The goal of this study was to evaluate the potential validity of salivary cytokines as biomarkers of immune dysregulation in RTT.

Methods

Saliva samples from 16 individuals with RTT (all female; age range 2–40 years) and 16 healthy control females (age range 2–40 years) were analyzed for concentrations of 12 cytokines. Between-group differences in concentrations, and correlations with clinical severity in the RTT group were evaluated.

Results

Concentrations of several salivary cytokines (IL-1β, IL-6, IL-8, IL-10, GM-CSF, TNF-α, and VEGF) were increased in RTT compared to controls. The same cytokines showed significant positive correlations with clinical severity scores. There were no differences in concentrations of IL-2, IL-4, IL-5, IL-12p70, and IFN-γ.

Conclusion

The results suggest that salivary cytokines may be a possible indicator of immune dysregulation in RTT. Future research should investigate whether these results can be applied to other neurodevelopmental disorders. Highlights • Immune dysregulation may play a role in the development of Rett syndrome (RTT), a disorder caused by mutations of the MECP2 gene.• Concentrations of several salivary cytokines were increased in RTT compared to controls.• These same cytokines showed significant positive correlations with clinical severity scores.• Results suggest that salivary cytokines may be a possible indicator of immune dysregulation in RTT.

SUBMITTER: Byiers B

PROVIDER: S-EPMC8474566 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe human gut microbiota directly affects human health, and its alteration can lead to gastrointestinal abnormalities and inflammation. Rett syndrome (RTT), a progressive neurological disorder mainly caused by mutations in MeCP2 gene, is commonly associated with gastrointestinal dysfunctions and constipation, suggesting a link between RTT's gastrointestinal abnormalities and the gut microbiota. The aim of this study was to evaluate the bacterial and fungal gut microbiota in a cohort of RTT subjects integrating clinical, metabolomics and metagenomics data to understand if changes in the gut microbiota of RTT subjects could be associated with gastrointestinal abnormalities and inflammatory status.ResultsOur findings revealed the occurrence of an intestinal sub-inflammatory status in RTT subjects as measured by the elevated values of faecal calprotectin and erythrocyte sedimentation rate. We showed that, overall, RTT subjects harbour bacterial and fungal microbiota altered in terms of relative abundances from those of healthy controls, with a reduced microbial richness and dominated by microbial taxa belonging to Bifidobacterium, several Clostridia (among which Anaerostipes, Clostridium XIVa, Clostridium XIVb) as well as Erysipelotrichaceae, Actinomyces, Lactobacillus, Enterococcus, Eggerthella, Escherichia/Shigella and the fungal genus Candida. We further observed that alterations of the gut microbiota do not depend on the constipation status of RTT subjects and that this dysbiotic microbiota produced altered short chain fatty acids profiles.ConclusionsWe demonstrated for the first time that RTT is associated with a dysbiosis of both the bacterial and fungal component of the gut microbiota, suggesting that impairments of MeCP2 functioning favour the establishment of a microbial community adapted to the costive gastrointestinal niche of RTT subjects. The altered production of short chain fatty acids associated with this microbiota might reinforce the constipation status of RTT subjects and contribute to RTT gastrointestinal physiopathology.