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BMC Gastroenterology
Published in: BMC Gastroenterology 1/2018

Open Access 01-12-2018 | Research article

Intestinal Candida parapsilosis isolates from Rett syndrome subjects bear potential virulent traits and capacity to persist within the host

Authors: Francesco Strati, Antonio Calabrò, Claudio Donati, Claudio De Felice, Joussef Hayek, Olivier Jousson, Silvia Leoncini, Daniela Renzi, Lisa Rizzetto, Carlotta De Filippo, Duccio Cavalieri

Published in: BMC Gastroenterology | Issue 1/2018

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Abstract

Background

Rett syndrome (RTT) is a neurological disorder mainly caused by mutations in MeCP2 gene. It has been shown that MeCP2 impairments can lead to cytokine dysregulation due to MeCP2 regulatory role in T-helper and T-reg mediated responses, thus contributing to the pro-inflammatory status associated with RTT. Furthermore, RTT subjects suffer from an intestinal dysbiosis characterized by an abnormal expansion of the Candida population, a known factor responsible for the hyper-activation of pro-inflammatory immune responses. Therefore, we asked whether the intestinal fungal population of RTT subjects might contribute the sub-inflammatory status triggered by MeCP2 deficiency.

Methods

We evaluated the cultivable gut mycobiota from a cohort of 50 RTT patients and 29 healthy controls characterizing the faecal fungal isolates for their virulence-related traits, antifungal resistance and immune reactivity in order to elucidate the role of fungi in RTT’s intestinal dysbiosis and gastrointestinal physiology.

Results

Candida parapsilosis, the most abundant yeast species in RTT subjects, showed distinct genotypic profiles if compared to healthy controls’ isolates as measured by hierarchical clustering analysis from RAPD genotyping. Their phenotypical analysis revealed that RTT’s isolates produced more biofilm and were significantly more resistant to azole antifungals compared to the isolates from the healthy controls. In addition, the high levels of IL-1β and IL-10 produced by peripheral blood mononuclear cells and the mixed Th1/Th17 cells population induced by RTT C. parapsilosis isolates suggest the capacity of these intestinal fungi to persist within the host, being potentially involved in chronic, pro-inflammatory responses.

Conclusions

Here we demonstrated that intestinal C. parapsilosis isolates from RTT subjects hold phenotypic traits that might favour the previously observed low-grade intestinal inflammatory status associated with RTT. Therefore, the presence of putative virulent, pro-inflammatory C. parapsilosis strains in RTT could represent an additional factor in RTT’s gastrointestinal pathophysiology, whose mechanisms are not yet clearly understood.
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Metadata
Title
Intestinal Candida parapsilosis isolates from Rett syndrome subjects bear potential virulent traits and capacity to persist within the host
Authors
Francesco Strati
Antonio Calabrò
Claudio Donati
Claudio De Felice
Joussef Hayek
Olivier Jousson
Silvia Leoncini
Daniela Renzi
Lisa Rizzetto
Carlotta De Filippo
Duccio Cavalieri
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2018
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-018-0785-z

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