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BMC Gastroenterol. 2018 May 2;18(1):57. doi: 10.1186/s12876-018-0785-z.

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

Author information

1
Computational Biology Research Unit, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, 38010, San Michele all'Adige, Italy.
2
Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123, Trento, Italy.
3
Present address: T Cell Development Lab, Institute for Research in Biomedicine, Università della Svizzera Italiana, Via Vincenzo Vela 6, CH-6500, Bellinzona, Switzerland.
4
Department of Experimental and Clinical Biomedical Sciences, Gastroenterology Unit, University of Florence, Viale Morgagni 40, 50139, Florence, Italy.
5
Neonatal Intensive Care Unit, University Hospital AOUS, Viale Bracci 16, 53100, Siena, Italy.
6
Child Neuropsychiatry Unit, University Hospital AOUS, Viale Bracci 16, 53100, Siena, Italy.
7
Nutrition and Nutrigenomics Unit, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, 38010, San Michele all'Adige, Italy.
8
Institute of Agriculture Biology and Biotechnology (IBBA), National Research Council (CNR), Via Moruzzi 1, 56124, Pisa, Italy.
9
Department of Biology, University of Florence, Via Madonna del Piano 6, 50019, Sesto Fiorentino, Florence, Italy. duccio.cavalieri@unifi.it.

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.

KEYWORDS:

Candida parapsilosis; Dysbiosis; Rett syndrome

PMID:
29720131
PMCID:
PMC5930502
DOI:
10.1186/s12876-018-0785-z
[Indexed for MEDLINE]
Free PMC Article

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