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Should we evaluate intestinal microbiota of pediatric patients undergoing hematopoietic stem cell transplantation?

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The interaction of gut microbiota and hematopoietic stem cell transplantation (HSCT) has been studied in several aspects, as composition, diversity, and metabolics products of microbiota. The present work aimed to… Click to show full abstract

The interaction of gut microbiota and hematopoietic stem cell transplantation (HSCT) has been studied in several aspects, as composition, diversity, and metabolics products of microbiota. The present work aimed to characterize the gut microbiota of pediatric patients prior to HSCT in a university hospital in South of Brazil. Until now, it is the first study in Brazil about the topic. Sampling was performed for convenience. Patients between 4and 17-years-old undergoing HSCT in the given period were invited to participate. We collected the sample once the patient was admitted. Patients without adequate fecal sample were excluded from the study. Clinical information was obtained from the medical records, within 90 days after transplantation. For the metagenomic analysis, the V4 hypervariable region of the bacterial 16S ribosomal RNA gene was sequenced on the Ion Torrent Personal Genome Machine (PGM, Thermo Fisher Scientific, Waltham, MA, USA). The sequencing data were processed using the QIIME software, according to the recommendations of the Brazilian Microbiome Project-BMP [1]. Owing to the low number of samples and a high number of possible confounders, it was decided not to perform statistical tests of correlation but describe the outcomes, together with relative abundance and alpha diversity. This project was approved by the institution’s Ethics Committee under number 16–0669. All patients or relatives signed an informed consent before the inclusion on the study. From April 2017 to November 2018, 20 patients met the inclusion criteria and agreed to participate. Of these, seven patients were excluded. Six could not collect the fecal sample in the appropriate period, and one patient did not have DNA amplification in the sample collected. Table 1 presents the main information of the patients evaluated. The total number of counts was 776,904. The predominant phyla were Bacteroidetes, Proteobacteria, Firmicutes, and Actinobacteria. Five patients (P2, P6, P9, P10, P11) presented abundance >90% of a single phylum. The reasons for death were sepsis (P6, P10, P11, and P12) and acute respiratory distress syndrome (P2 and P5). Predominance of Enterococcus—Firmicutes phylum— was indicated as a possible association with graft-versushost disease (GVHD) and increased risk of bacteremia [2]. We observed the occurrence of GVHD in the GIT and death by sepsis in a patient (P6) with such predominance (genera Enterococcus, Streptococcus and Lactobacillus). On the other hand, Firmicutes phylum also has been considered as a protector of GVHD due to the presence of non-inflammatory Clostridium species, as described by Simms-Waldrip et al. [3]. Of the other two patients with predominance of Firmicutes, P1 did not develop clinical complications (Ruminococceae and Lachnospiraceae), while P12 died of sepsis (Leuconostoc, Ruminococceae, and Lachnospiraceae). Patients with predominance of phylum Bacteroidetes presented genus Bacteroides as major component. Bacteroidetes was reported as a protector for GVHD by Doki et al. [4] at the pre-transplant stage, and after transplantation by Biagi et al. [5]. Two patients with predominance of this phylum died at D50 (P2) and after D100 (P5), and one (P13) developed acute GVHD (aGVHD) in skin. Study conducted at Unidade de Ambiente Protegido, at Hospital de Clínicas de Porto Alegre

Keywords: cell transplantation; stem cell; transplantation; hematopoietic stem; gvhd; predominance

Journal Title: Bone Marrow Transplantation
Year Published: 2019

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