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Stem cell transplant microbiome

Yeon Joo Lee, Esther P Arguello, Robert R Jenq, Eric Littmann, Grace J Kim, Liza C Miller, Lilan Ling, Cesar Figueroa, Elizabeth Robilotti, Miguel-Angel Perales, Juliet N Barker, Sergio Giralt, Marcel R M van den Brink, Eric G Pamer, Ying Taur
Background.: Clostridium difficile infection (CDI) is a frequent complication in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), who receive intensive treatments that significantly disrupt the intestinal microbiota. In this study, we examined the microbiota composition of allo-HSCT recipients to identify bacterial colonizers that confer protection against CDI following engraftment. Methods.: Feces collected from adult recipients allo-HSCT at engraftment were analyzed; 16S rRNA genes were sequenced and analyzed from each sample...
January 30, 2017: Journal of Infectious Diseases
Elan Gorshein, Catherine Wei, Susan Ambrosy, Shanna Budney, Juliana Vivas, Angelika Shenkerman, Jacqueline Manago, Mary Kate McGrath, Anne Tyno, Yong Lin, Vimal Patel, Mecide Gharibo, Dale Schaar, Robert R Jenq, Hossein Khiabanian, Roger Strair
Graft-versus-host disease (GVHD) is a major adverse effect associated with allogeneic stem cell transplant. Previous studies in mice indicated that administration of the probiotic Lactobacillus rhamnosus GG can reduce the incidence of GVHD after hematopoietic stem cell transplant. Here we report results from the first randomized probiotic enteric regimen trial in which allogenic hematopoietic stem cell patients were supplemented with Lactobacillus rhamnosus GG. Gut microbiome analysis confirmed a previously reported gut microbiome association with GVHD...
March 3, 2017: Clinical Transplantation
Antiopi Varelias, Kate L Ormerod, Mark D Bunting, Motoko Koyama, Kate H Gartlan, Rachel D Kuns, Nancy Lachner, Kelly R Locke, Chun Y Lim, Andrea S Henden, Ping Zhang, Andrew D Clouston, Sumaira Z Hasnain, Michael A McGuckin, Bruce R Blazar, Kelli P A MacDonald, Philip Hugenholtz, Geoffrey R Hill
Donor T-cell-derived IL-17A can mediate late immunopathology in graft-versus-host disease (GVHD), however protective roles remain unclear. Using multiple cytokine and cytokine receptor subunit knockout mice we demonstrate that stem cell transplant (SCT) recipients lacking the ability to generate or signal IL-17 develop intestinal hyper-acute GVHD. This protective effect is restricted to the molecular interaction of IL-17A and/or IL-17F with the IL-17RA/C receptor. The protection from GVHD afforded by IL-17A required secretion from, and signaling in, both hematopoietic and non-hematopoietic host tissue...
January 30, 2017: Blood
Vikram M Raghunathan, Iris Sheng, Seah H Lim
The intestinal microbiota is a diverse and dynamic ecosystem that is increasingly understood to play a vital role in human health. Hematopoietic stem cell transplant recipients undergo prolonged exposure to antimicrobials, chemotherapeutic agents, and immunosuppressants, resulting in profound shifts in the gut microbiome. A growing body of research has revealed the ways in which these microbiologic shifts shape immune modulation, affecting susceptibility to infections and graft-versus-host disease, the two major post-transplant complications in this population...
December 3, 2016: Journal of Translational Medicine
C P Furquim, G M S Soares, L L Ribeiro, M A Azcarate-Peril, N Butz, J Roach, K Moss, C Bonfim, C C Torres-Pereira, F R F Teles
Fanconi anemia (FA) is a rare genetic disease characterized by chromosomal instability and impaired DNA damage repair. FA patients develop oral squamous cell carcinoma (OSCC) earlier and more frequently than the general population, especially after hematopoietic stem cell transplantation (HSCT). Although evidence of an etiological role of the local microbiome and carcinogenesis has been mounting, no information exists regarding the oral microbiome of FA patients. The aim of this study was to explore the salivary microbiome of 61 FA patients regarding their oral health status and OSCC risk factors...
March 2017: Journal of Dental Research
Ying Taur
Studies of the microbiome in the setting of haematopoietic stem cell transplantation (SCT) have shown evidence that intestinal microbes appear to play a particularly important role in determining the outcome of treatment, impacting complications such as infection or graft-versus-host disease. Past studies may vary in terms of the level at which the microbiome is examined, leading to different but overlapping systems of taxonomy or nomenclature, which may be difficult for non-specialists to understand. This article will review the current body of work examining the clinical impact of the microbiome on SCT, and will provide a basic framework for the bacterial phylogenetic structure upon which the results of these studies rest...
November 16, 2016: Virulence
Juan Gea-Banacloche, Krishna V Komanduri, Paul Carpenter, Sophie Paczesny, Stefanie Sarantopoulos, Jo-Anne Young, Nahed El Kassar, Robert Q Le, Kirk R Schultz, Linda M Griffith, Bipin N Savani, John R Wingard
Immune reconstitution after hematopoietic stem cell transplantation (HCT) beyond 1 year is not completely understood. Many transplant recipients who are free of graft-versus-host disease (GVHD) and not receiving any immunosuppression more than 1 year after transplantation seem to be able to mount appropriate immune responses to common pathogens and respond adequately to immunizations. However, 2 large registry studies over the last 2 decades seem to indicate that infection is a significant cause of late mortality in some patients, even in the absence of concomitant GVHD...
October 14, 2016: Biology of Blood and Marrow Transplantation
J Whangbo, J Ritz, A Bhatt
Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many patients with severe benign and malignant hematologic disorders. The success of allogeneic HSCT is limited by the development of transplant-related complications such as acute graft-versus-host disease (GvHD). Early pre-clinical studies suggested that intestinal microflora contribute to the pathogenesis of acute GvHD, and that growth suppression or eradication of intestinal bacteria prevented the development of acute GvHD even in MHC-mismatched transplants...
February 2017: Bone Marrow Transplantation
Alessandro Villa, Stephen T Sonis
INTRODUCTION: Oral mucositis is a frequent and devastating toxicity secondary to cancer treatment, which may affect 20-40% of patients receiving conventional chemotherapy and 60-85% of patients undergoing hematopoietic stem cell transplantation. The pathobiology of mucositis includes a complex cascade of biologic events in which pro-inflammatory cytokines, ROS, second messengers, and the oral microbiome contribute to tissue damage of the oral mucosa. Management strategies to oral mucositis secondary to chemotherapy include preventative measures and therapeutic approaches...
September 2016: Expert Opinion on Pharmacotherapy
Frank Stämmler, Joachim Gläsner, Andreas Hiergeist, Ernst Holler, Daniela Weber, Peter J Oefner, André Gessner, Rainer Spang
BACKGROUND: Next-generation 16S ribosomal RNA gene sequencing is widely used to determine the relative composition of the mammalian gut microbiomes. However, in the absence of a reference, this does not reveal alterations in absolute abundance of specific operational taxonomic units if microbial loads vary across specimens. RESULTS: Here we suggest the spiking of exogenous bacteria into crude specimens to quantify ratios of absolute bacterial abundances. We use the 16S rDNA read counts of the spike-in bacteria to adjust the read counts of endogenous bacteria for changes in total microbial loads...
2016: Microbiome
Emmanuel Montassier, Gabriel A Al-Ghalith, Tonya Ward, Stephane Corvec, Thomas Gastinne, Gilles Potel, Phillipe Moreau, Marie France de la Cochetiere, Eric Batard, Dan Knights
BACKGROUND: Bacteremia, or bloodstream infection (BSI), is a leading cause of death among patients with certain types of cancer. A previous study reported that intestinal domination, defined as occupation of at least 30 % of the microbiota by a single bacterial taxon, is associated with BSI in patients undergoing allo-HSCT. However, the impact of the intestinal microbiome before treatment initiation on the risk of subsequent BSI remains unclear. Our objective was to characterize the fecal microbiome collected before treatment to identify microbes that predict the risk of BSI...
April 28, 2016: Genome Medicine
P S Heeger
Research reports presented at the American Transplant Congress 2015 provided an array of basic science findings of relevance to the transplant community. Among key themes is the concept that ischemia-reperfusion injury and early posttransplantation inflammation is linked to adaptive alloimmunity and transplant injury. Molecular and cellular mechanisms contributing to these interactions were highlighted. The relevance of understanding how blocking costimulation, including CD40/CD154 interactions, affects various aspects of the alloimmune response was enhanced by the description of preclinical studies demonstrating efficacy of a unique, blocking anti-CD40 monoclonal antibody that could potentially be used in humans...
November 2015: American Journal of Transplantation
M Nedim Ince, Bruce R Blazar, Michael B Edmond, Guido Tricot, Michael J Wannemuehler
The human intestine contains 10 bacteria, which outnumber the mammalian cells 10-fold. Certain other commensal or infectious agents, like helminthic parasites, become members of this microbial ecosystem, especially in populations living under less hygienic conditions. Intestinal microbes, also called the microbiome or microbiota, shape the host immune reactivity to self and nonself throughout life. Changes in microbiome composition may impair the maturation of immune regulatory pathways and predispose the host to develop various forms of inflammatory disorders, like Crohn's disease or ulcerative colitis...
January 2016: Inflammatory Bowel Diseases
Robert R Jenq
In this issue of Blood, Weber and colleagues demonstrate that in the first 10 days following allogeneic hematopoietic transplantation, urinary 3-indoxyl sulfate is a biomarker of intestinal microbiota health and predicts reduced intestinal graft-versus-host disease (GVHD) and treatment-related mortality, as well as improved overall survival.
October 1, 2015: Blood
Daniela Weber, Peter J Oefner, Andreas Hiergeist, Josef Koestler, André Gessner, Markus Weber, Joachim Hahn, Daniel Wolff, Frank Stämmler, Rainer Spang, Wolfgang Herr, Katja Dettmer, Ernst Holler
Indole, which is produced from l-tryptophan by commensal bacteria expressing tryptophanase, not only is an important intercellular signal in microbial communities, but also modulates mucosal barrier function and expression of pro- and anti-inflammatory genes by intestinal epithelial cells. Here, we hypothesized that decreased urinary excretion of 3-indoxyl sulfate (3-IS), the major conjugate of indole found in humans, may be a marker of gut microbiota disruption and increased risk of developing gastrointestinal (GI) graft-versus-host-disease...
October 1, 2015: Blood
E Montassier, T Gastinne, P Vangay, G A Al-Ghalith, S Bruley des Varannes, S Massart, P Moreau, G Potel, M F de La Cochetière, E Batard, D Knights
BACKGROUND: Chemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation (HSCT). Chemotherapy leads to several side effects, with gastrointestinal (GI) mucositis being one of the most frequent. Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome. AIM: To identify functional mechanisms by which the intestinal microbiome may play a key role in the pathophysiology of GI mucositis, we applied high-throughput DNA-sequencing analysis to identify microbes and microbial functions that are modulated following chemotherapy...
September 2015: Alimentary Pharmacology & Therapeutics
Stephen M Vindigni, Christina M Surawicz
The intestinal microbiome is critical to digestion, metabolism and protection from pathogenic organisms. Dysbiosis, or alteration of this microbiome, can result in Clostridium difficile infection and may play a role in other conditions. Patients undergoing solid organ transplantation (e.g., kidney, lung, liver, small bowel) and hematopoietic stem cell transplantation have a shift in the gut microbiome with a decrease in predominant organisms, a loss of bacterial diversity and emergence of a new dominant population...
2015: Expert Review of Clinical Immunology
Melanie Wong
Fifty years ago, in 1964, our understanding of the immune system was very rudimentary. Gell and Coombs had just described classes of hypersensitivity reactions, and Bruton had described and commenced immunoglobulin replacement in agammaglobulinaemia. The distinction between T and B cells was not identified and characterised until the 1960s and 1970s. This was followed by increasing recognition of T and B cell collaboration in immune responses and identification of significant immunodeficiencies. CD4 and CD8 T cells were only recognised in the 1970s and 1980s...
February 2015: Journal of Paediatrics and Child Health
Xingmin Wang, Yonghong Yang, Mark M Huycke
OBJECTIVE: Commensal bacteria and innate immunity play a major role in the development of colorectal cancer (CRC). We propose that selected commensals polarise colon macrophages to produce endogenous mutagens that initiate chromosomal instability (CIN), lead to expression of progenitor and tumour stem cell markers, and drive CRC through a bystander effect. DESIGN: Primary murine colon epithelial cells were repetitively exposed to Enterococcus faecalis-infected macrophages, or purified trans-4-hydroxy-2-nonenal (4-HNE)-an endogenous mutagen and spindle poison produced by macrophages...
March 2015: Gut
Ernst Holler, Peter Butzhammer, Karin Schmid, Christian Hundsrucker, Josef Koestler, Katrin Peter, Wentao Zhu, Daniela Sporrer, Thomas Hehlgans, Marina Kreutz, Barbara Holler, Daniel Wolff, Matthias Edinger, Reinhard Andreesen, John E Levine, James L Ferrara, Andre Gessner, Rainer Spang, Peter J Oefner
Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria...
May 2014: Biology of Blood and Marrow Transplantation
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