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Stem cell transplant microbiome

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https://www.readbyqxmd.com/read/28625828/precision-monitoring-of-immunotherapies-in-solid-organ-and-hematopoietic-stem-cell-transplantation
#1
Rose Diloreto, Kiran Khush, Iwijn De Vlaminck
Pharmacological immunotherapies are a key component of post-transplant therapy in solid-organ and hematopoietic stem cell transplantation. In current clinical practice, immunotherapies largely follow a one-size fits all approach, leaving a large portion of transplant recipients either over- or under-immunosuppressed, and consequently at risk of infections or immune-mediated complications. Our goal here is to review recent and rapid advances in precision and genomic medicine approaches to monitoring of post-transplant immunotherapies...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28581444/altered-homeostatic-regulation-of-innate-and-adaptive-immunity-in-lower-gastrointestinal-tract-gvhd-pathogenesis
#2
James Lm Ferrara, Christopher M Smith, Julia Sheets, Pavan Reddy, Jonathan S Serody
Lower gastrointestinal (GI) tract graft-versus-host disease (GVHD) is the predominant cause of morbidity and mortality from GVHD after allogeneic stem cell transplantation. Recent data indicate that lower GI tract GVHD is a complicated process mediated by donor/host antigenic disparities. This process is exacerbated by significant changes to the microbiome, and innate and adaptive immune responses that are critical to the induction of disease, persistence of inflammation, and a lack of response to therapy. Here, we discuss new insights into the biology of lower GI tract GVHD and focus on intrinsic pathways and regulatory mechanisms crucial to normal intestinal function...
June 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28498996/protective-factors-in-the-intestinal-microbiome-against-clostridium-difficile-infection-in-recipients-of-allogeneic-hematopoietic-stem-cell-transplantation
#3
Yeon Joo Lee, Esther S 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 after engraftment. Methods: Feces collected from adult recipients allo-HSCT at engraftment were analyzed; 16S ribosomal RNA genes were sequenced and analyzed from each sample...
April 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28438184/microbiota-activated-cd103-dcs-stemming-from-microbiota-adaptation-specifically-drive-%C3%AE-%C3%AE-t17-proliferation-and-activation
#4
Chris Fleming, Yihua Cai, Xuan Sun, Venkatakrishna R Jala, Feng Xue, Samantha Morrissey, Yu-Ling Wei, Yueh-Hsiu Chien, Huang-Ge Zhang, Bodduluri Haribabu, Jian Huang, Jun Yan
BACKGROUND: IL-17-producing γδT cells (γδT17) promote autoinflammatory diseases and cancers. Yet, γδT17 peripheral regulation has not been thoroughly explored especially in the context of microbiota-host interaction. The potent antigen-presenting CD103(+) dendritic cell (DC) is a key immune player in close contact with both γδT17 cells and microbiota. This study presents a novel cellular network among microbiota, CD103(+) DCs, and γδT17 cells. METHODS: Immunophenotyping of IL-17r(-/-) mice and IL-17r(-/-) IRF8(-/-) mice were performed by ex vivo immunostaining and flow cytometric analysis...
April 24, 2017: Microbiome
https://www.readbyqxmd.com/read/28329030/protective-factors-in-the-intestinal-microbiome-against-clostridium-difficile-infection-in-recipients-of-allogeneic-hematopoietic-stem-cell-transplantation
#5
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
https://www.readbyqxmd.com/read/28256022/lactobacillus-rhamnosus-gg-probiotic-enteric-regimen-does-not-appreciably-alter-the-gut-microbiome-or-provide-protection-against-gvhd-after-allogeneic-hematopoietic-stem-cell-transplantation
#6
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
https://www.readbyqxmd.com/read/28137828/acute-graft-versus-host-disease-is-regulated-by-an-il-17-sensitive-microbiome
#7
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 interleukin-17A (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 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-17 receptor A/C (IL-17RA/C). The protection from GVHD afforded by IL-17A required secretion from, and signaling in, both hematopoietic and nonhematopoietic host tissue...
April 13, 2017: Blood
https://www.readbyqxmd.com/read/27912759/intestinal-dysbiosis-and-allogeneic-hematopoietic-progenitor-cell-transplantation
#8
REVIEW
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
https://www.readbyqxmd.com/read/27827319/the-salivary-microbiome-and-oral-cancer-risk-a-pilot-study-in-fanconi-anemia
#9
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
https://www.readbyqxmd.com/read/27805463/intestinal-microbiome-changes-and-stem-cell-transplantation-lessons-learned
#10
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
https://www.readbyqxmd.com/read/27751936/national-institutes-of-health-hematopoietic-cell-transplantation-late-effects-initiative-the-immune-dysregulation-and-pathobiology-working-group-report
#11
REVIEW
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...
June 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27526283/antibiotic-mediated-modification-of-the-intestinal-microbiome-in-allogeneic-hematopoietic-stem-cell-transplantation
#12
REVIEW
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
https://www.readbyqxmd.com/read/27477002/pharmacotherapy-for-the-management-of-cancer-regimen-related-oral-mucositis
#13
REVIEW
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
https://www.readbyqxmd.com/read/27329048/adjusting-microbiome-profiles-for-differences-in-microbial-load-by-spike-in-bacteria
#14
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...
June 21, 2016: Microbiome
https://www.readbyqxmd.com/read/27121964/pretreatment-gut-microbiome-predicts-chemotherapy-related-bloodstream-infection
#15
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
https://www.readbyqxmd.com/read/26460718/what-s-hot-what-s-new-in-basic-science-report-from-the-american-transplant-congress-2015
#16
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
https://www.readbyqxmd.com/read/26457381/understanding-luminal-microorganisms-and-their-potential-effectiveness-in-treating-intestinal-inflammation
#17
REVIEW
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
https://www.readbyqxmd.com/read/26429966/how-s-your-microbiota-let-s-check-your-urine
#18
COMMENT
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
https://www.readbyqxmd.com/read/26209659/low-urinary-indoxyl-sulfate-levels-early-after-transplantation-reflect-a-disrupted-microbiome-and-are-associated-with-poor-outcome
#19
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
https://www.readbyqxmd.com/read/26147207/chemotherapy-driven-dysbiosis-in-the-intestinal-microbiome
#20
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
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