Intestinal mycobiota composition and changes in children with thalassemia who underwent allogeneic hematopoietic stem cell transplantation

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) alters the diversity of the intestinal bacterial microbiota. This study aimed to evaluate human mycobiota composition pre-HSCT and post-HSCT in children with thalassemia.Method: Ten children with thalassemia undergoing allogeneic HSCT were enrolled.The stool samples were collected before the transplantation regimen, before the transplant day, and +15, +30 days, and three months after transplantation. Stool samples were also collected from the donor and the patient's caregivers. Gut mycobiota composition was evaluated with metagenomic analysis.Results: Pretransplant mycobiota of children with thalassemia (the predominant genus was Saccharomyces, 64.1%) has been shown to approximate the diverse mycobiota compositions of healthy adult donors but becomes altered (lower diversity) following transplant procedures. Three months after HSCT, phyla Ascomycota and Basidiomycota were 83.4% and 15.6%, respectively. The predominant species were Sacc-aharomyces_uc and Saccharomyces cerevisiae (phylum Ascomycota); we also observed Malassezia restricta and Malassezia globosa (phylum Basidiomycota) (∼13%). On day 90 after HSCT, we observed 65.3% M. restricta and 18.4% M. globosa predominance at the species level in a four-year-old boy with acute graft-versus-host disease (GVHD) (skin and gut involvement) 19 days after transplantation included. Conclusion:The mycobiota composition of children with thalassemia altered after HSCT. We observed Malassezia predominance in a child with GVHD. Further studies in children with GVHD will identify this situation.

Gut microbiota trajectory in β‐thalassemia major children who underwent allogeneic hematopoietic stem cell transplantation

“…In this study, the Shannon index was low and similar between patients before transplantation but significantly lower on days 15 and 30 after transplantation. 19 Another study found that HSCT resulted in a profound disturbance of the gut ecosystem, measured by the loss of about 30% of the pre-HSCT alpha diversity. Additionally, the mean value of weighted UniFrac distances among pre-HSCT samples was significantly lower than post-HSCT samples, demonstrating the increased inter-subject gut microbiota diversity after transplantation.…”

“…In recent years, increasing evidence has indicated that posttransplant microbiota deviation is closely associated with allo-HSCT outcomes, including infectious complications, graft-versus-host disease (GVHD), disease relapse, and mortality. 7 Previous studies have demonstrated the role of gut microbiota in metabolic, cardiovascular, and mental diseases. 8 However, little research on hematological diseases is available, especially in pediatric patients.…”

The Impact of Human Microbiotas in Hematopoietic Stem Cell and Organ Transplantation

“…The mycobiome has also been investigated in the context of HSCT. In a first-of-its-kind proof-of-concept study, a metagenomic analysis of the gut mycobiota composition of ten children with thalassemia undergoing allogeneic HSCT was done at four different time points (transplant day, 15 days post-transplant, 30 days post-transplant, and 90 days post-transplant) to evaluate how HSCT impacts the diversity of the human gut mycobiota ( 106 ). No notable changes in the gut mycobiome were observed up to a month following transplantation, and the dominating phylum was Ascomycota .…”

“…However, more focused future investigations into the relationship of Malassezia spp. and GVHD in HSCT patients may help in the development of novel microbial biomarkers as well as targeted therapeutic interventions involving this genus ( 106 ). Although the bacteriome, virome, and mycobiome individually provide interesting insights with potential clinical relevance, a siloed understanding of these individual biomes may not be representative of the community dynamics at play.…”

MetaGut: Insights into gut microbiomes in stem cell transplantation by comprehensive shotgun long-read sequencing

“…The vast majority of microbiome studies were performed using ribosomal DNA (rDNA) based sequencing methods designed for bacterial and fungal 16/23S, 18/28S or ITS region rDNA sequences, respectively, thus neglecting the archaeome, non-fungal eukaryome, and the DNA virome (Borrel et al 2020, Kurilshikov et al 2021, Richard and Sokol 2019, Sen and Thummer 2022, Stockdale and Hill 2021, Vandeputte et al 2017, Yalcin et al 2022, Zhernakova et al 2016). rDNA sequencing is a well-established, scalable, and cost-effective technology; it has, however, important limitations as it bears potential amplification-induced biases in bacteriome/mycobiome composition estimates and challenges in reliably assigning accurate species - or genus-level labels (Edgar 2018).…”