Integrated meta-omic analyses of the gastrointestinal tract microbiome in patients undergoing allogeneic hematopoietic stem cell transplantation.

in Translational Research: the Journal of Laboratory and Clinical Medicine (2017)

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most ... [more ▼]

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most notably graft-versus-host disease (GvHD). However, it is presently unknown whether this relationship is causal or consequential. Here, we performed an integrated meta-omic analysis to probe deeper into the GIT microbiome changes during allo-HSCT and its accompanying treatments. We used 16S and 18S rRNA gene amplicon sequencing to resolve archaea, bacteria, and eukaryotes within the GIT microbiomes of 16 patients undergoing allo-HSCT for the treatment of hematologic malignancies. These results revealed a major shift in the GIT microbiome after allo-HSCT including a marked reduction in bacterial diversity, accompanied by only limited changes in eukaryotes and archaea. An integrated analysis of metagenomic and metatranscriptomic data was performed on samples collected from a patient before and after allo-HSCT for acute myeloid leukemia. This patient developed severe GvHD, leading to death 9 months after allo-HSCT. In addition to drastically decreased bacterial diversity, the post-treatment microbiome showed a higher overall number and higher expression levels of antibiotic resistance genes (ARGs). One specific Escherichia coli strain causing a paravertebral abscess was linked to GIT dysbiosis, suggesting loss of intestinal barrier integrity. The apparent selection for bacteria expressing ARGs suggests that prophylactic antibiotic administration may adversely affect the overall treatment outcome. We therefore assert that such analyses including information about the selection of pathogenic bacteria expressing ARGs may assist clinicians in "personalizing" regimens for individual patients to improve overall outcomes. [less ▲]

Dynamic change of host gastrointestinal microbiome and immune status in relation to mucosal barrier effects during chemotherapy and immune ablative intervention in humans

Poster (2014, April)

The human gastrointestinal tract is colonized by communities of endogenous microbes, commonly referred to as the microbiome. Here, the microbiota are in close contact with the host intestinal mucosa and ... [more ▼]

The human gastrointestinal tract is colonized by communities of endogenous microbes, commonly referred to as the microbiome. Here, the microbiota are in close contact with the host intestinal mucosa and its innate and adaptive immune systems. The fact that certain stimuli induce an inflammatory response whereas others induce tolerance suggests, that the host immune system interacts with the microbiota and vice versa in different ways. However, the exact details of theses interactions remain largely unknown. It is known that cancer treatment can result in severe adverse effects like mucositis and in combination with allogeneic stem cell transplantation (Tx), in graft-versus host disease (GvHD). However, there is at present only sparse information available on the effects of chemotherapy on the intestinal microbiota and resulting changes in microbiome-immune system interactions. Almost no data exists on the effect of allogeneic stem cell Tx on the composition of the gastrointestinal microbiota. In this project, we are studying the complex interactions between the host and the intestinal microbiota after chemotherapy with or without allogeneic Tx and the occurrence of severe adverse side effects such as mucositis and GvHD. Using a systems biology approach including metagenomics and RNAseq, fecal samples and blood plasma samples from patients undergoing these treatments for malignancies will be analysed to identify the composition of the gastrointestinal microbiome and bacterial small RNAs. The main research hypothesis is that there are quantitative and qualitative changes in the gastrointestinal microbiome following chemotherapy and allogeneic Tx which are linked to the immune status of the patients and possible treatment side-effects, in particular mucositis and GvHD. We aim to provide knowledge on how the host's intestinal mucosa and immune system influence the gastrointestinal microbiome and on the role and involvement of the gastrointestinal microbiota in development in mucositis and GvHD. Importantly, this could help in the formulation of measures to prevent mucositis and GvHD development. [less ▲]

Formanalyse in der Magnetresonanztomographie - Landmarken und Objektdifferenzierung bei retroperitonealen Tumoren im Kindesalter

in Bulletin de la Société des Sciences Médicales du Grand-Duché de Luxembourg (2010), 1