Changes in the gut mycobiome in pediatric patients in relation to the clinical activity of Crohn's disease

Abstract

BACKGROUND Numerous studies have shown that in Crohn’s disease (CD), the gut microbiota is of great importance in the induction and maintenance of inflammation in the gastrointestinal tract. Until recently, studies have focused almost exclusively on bacteria in the gut. Lately, more attention has been paid to the role of intestinal fungi. AIM To study the gut mycobiome analysis of pediatric patients with CD (in different stages of disease activity) compared to healthy children. METHODS Fecal samples were collected from patients: With active, newly diagnosed CD ( n = 50); active but previously diagnosed and treated CD ( n = 16); non-active CD and who were in clinical remission ( n = 39) and from healthy volunteers ( n = 40). Fungal DNA was isolated from the samples . Next, next generation sequencing (MiSeq, Illumina) was performed. The composition of mycobiota was correlated with clinical and blood parameters. RESULTS Candida spp. were overrepresented in CD patients, while in the control group, the most abundant genus was Saccharomyces . In CD patients, the percentage of Malassezia was almost twice that of the control ( P < 0.05). In active CD patients, we documented a higher abundance of Debaryomyces hansenii ( D. hansenii ) compared to the non-active CD and control ( P < 0.05) groups. Moreover, statistically significant changes in the abundance of Mycosphaerella , Rhodotorula , and Microidium were observed. The analyses at the species level and linear discriminant analysis showed that in each group it was possible to distinguish a specific species characteristic of a given patient population. Moreover, we have documented statistically significant correlations between: D. hansenii and patient age (negative); C. zeylanoides and patient age (positive); C. dubliniensis and calprotectin (positive); C. sake and calprotectin (positive); and C. tropicalis and pediatric CD activity index (PCDAI) (positive). CONCLUSION Mycobiome changes in CD patients, and the positive correlation of some species with calprotectin or PCDAI, give strong evidence that fungi may be of key importance in the development of CD.

An integrative multi-omic analysis defines gut microbiota, mycobiota, and metabolic fingerprints in ulcerative colitis patients

“…In IBD patients, high levels of fungi with potential proinflammatory effects such as Candida and Malassezia and low levels of fungi with anti-inflammatory effects such as Saccharomyces were reported ( Krawczyk et al., 2023 ). In our study, Saccharomyces was effectively present in the CTRL network and positively correlated with Parabacteroides .…”

Persistent dysbiosis of duodenal microbiota in patients with controlled pediatric Crohn’s disease after resolution of inflammation

“…The efficacy of fecal microbiota transplantation (FMT) for Crohn’s disease further supports the importance of microbiota restoration as a part of treatment 60 . Recently, mycobiota have also been correlated with increased disease activity 61 . Thus, more extensive metagenomic studies to determine if recalcitrant dysbiosis in pediatric Crohn’s disease are warranted.…”

Research advancements and perspectives of inflammatory bowel disease: A comprehensive review

“…In UC or CD patients, the abundance of the phylum Proteobacteria, the genus Escherichia , the species Escherichia coli , and fungi such as Candida , Malassezia , and Epicoccum nigrum are higher, and the abundance of Saccharomyces and Akkermansia muciniphila are lower. 28 – 30 However, Reiss et al show that their retroauricular crease and lumbar region skin microbiota diversity is increased, including Delftia , Corynebacterium , and Pseudomonas . 31 In addition, fungi, increased in activate IBD patients and mice, activate dectin-1-Syk-NF-κB to enhance the glutaminolysis in CD4 + T cells, which contributes to the progression of IBD.…”