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Open accessJournal ArticleDOI: 10.1016/J.CRITREVONC.2021.103289

Recent insights into the role of the microbiome in malignant and benign hematologic diseases.

02 Mar 2021-Critical Reviews in Oncology Hematology (Elsevier)-Vol. 160, pp 103289-103289
Abstract: Growing evidence suggests the impact of microbiome alteration, named dysbiosis, on the development of neoplasms, infections, inflammatory diseases, and immuno-mediated disorders. Regarding hematologic diseases, most data regard hematopoietic stem cell transplant (HSCT). In this review, we systematically evaluate the studies concerning microbiome in malignant and benign hematologic disorders beyond HSCT. A permissive microbiota is associated to the development of hematologic malignancies (including acute leukemia, lymphoma, and multiple myeloma), as well as of iron deficiency anemia, autoimmune cytopenias, and aplastic anemia. This happens through various mechanisms; chronic inflammatory triggering, epithelial barrier alteration, antigen dissequestration, and molecular mimicry. Hematologic therapies (chemo and immunosuppression) may induce/worsen dysbiosis and favour disease progression and infectious complications. Antibiotics may also induce dysbiosis with possible long-term consequences. Finally, novel target therapies are likely to alter microbiome, inducing gut inflammation (i.e. small molecules such as tyrosine-kinase-inhibitors) or enhancing host's immune system (as observed with CAR-T cells and checkpoint inhibitors).

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Topics: Hematologic disease (61%), Dysbiosis (57%), Microbiome (57%)
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5 results found


Open accessJournal ArticleDOI: 10.3390/CANCERS13071532
26 Mar 2021-Cancers
Abstract: Autoimmune cytopenias (AICy) and autoimmune diseases (AID) can complicate both lymphoid and myeloid neoplasms, and often represent a diagnostic and therapeutic challenge. While autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) are well known, other rarer AICy (autoimmune neutropenia, aplastic anemia, and pure red cell aplasia) and AID (systemic lupus erythematosus, rheumatoid arthritis, vasculitis, thyroiditis, and others) are poorly recognized. This review analyses the available literature of the last 30 years regarding the occurrence of AICy/AID in different onco-hematologic conditions. The latter include chronic lymphocytic leukemia (CLL), lymphomas, multiple myeloma, myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), myeloproliferative neoplasms, and acute leukemias. On the whole, AICy are observed in up to 10% of CLL and with higher frequencies in certain subtypes of non-Hodgkin lymphoma, whilst they occur in less than 1% of low-risk MDS and CMML. AID are described in up to 30% of myeloid and lymphoid patients, including immune-mediated hemostatic disorders (acquired hemophilia, thrombotic thrombocytopenic purpura, and anti-phospholipid syndrome) that may be severe and fatal. Additionally, AICy/AID are found in about 10% of patients receiving hematopoietic stem cell transplant or treatment with new checkpoint inhibitors. Besides the diagnostic difficulties, these AICy/AID may complicate the clinical management of already immunocompromised patients.

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7 Citations


Open accessJournal ArticleDOI: 10.1177/11795549211024197
Zhuangzhuang Shi1, Mingzhi Zhang1Institutions (1)
17 Jun 2021-
Abstract: Lymphoid neoplasms encompass a heterogeneous group of malignancies with a predilection for immunocompromised individuals, and the disease burden of lymphoid neoplasms has been rising globally over ...

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Topics: Biomarker (medicine) (55%), Dysbiosis (51%)

1 Citations


Open accessJournal ArticleDOI: 10.3389/FIMMU.2021.751630
Abstract: Immune phenomena are increasingly reported in myeloid neoplasms, and include autoimmune cytopenias/diseases and immunodeficiency, either preceding or complicating acute myeloid leukemia, myelodysplastic syndromes (MDS), chronic myeloproliferative neoplasms, and bone marrow failure (BMF) syndromes. Autoimmunity and immunodeficiency are the two faces of a dysregulated immune tolerance and surveillance and may result, along with contributing environmental and genetic factors, in an increased incidence of both tumors and infections. The latter may fuel both autoimmunity and immune activation, triggering a vicious circle among infections, tumors and autoimmune phenomena. Additionally, alterations of the microbiota and of mesenchymal stem cells (MSCs) pinpoint to the importance of a permissive or hostile microenvironment for tumor growth. Finally, several therapies of myeloid neoplasms are aimed at increasing host immunity against the tumor, but at the price of increased autoimmune phenomena. In this review we will examine the epidemiological association of myeloid neoplasms with autoimmune diseases and immunodeficiencies, and the pivotal role of autoimmunity in the pathogenesis of MDS and BMF syndromes, including the paroxysmal nocturnal hemoglobinuria conundrum. Furthermore, we will briefly examine autoimmune complications following therapy of myeloid neoplasms, as well as the role of MSCs and microbiota in these settings.

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Topics: Myeloid leukemia (59%), Myeloid (56%), Immunodeficiency (54%) ... show more

Open accessJournal ArticleDOI: 10.1016/J.TRANSCI.2021.103320
Abstract: Whilst particular infectious bacteria are well-established to be associated with hematological diseases, more recent interest has focused on the entire microbial community of mucosal surfaces. In particular, the link between hematology and the microbiota (defined as the total assemblage of microorganisms in a mucosal environment)/ microbiome (i.e. the entire ecological habitat, including organisms, their genomes and environmental conditions) is becoming more well-known. Dysbiosis, or a change in the microbiome, has been linked to the development of neoplasms, infections, inflammatory illnesses, and immune-mediated disorders, according to growing data. Microbiota may influence distant tumor microenvironment through a variety of methods, including cytokine release control, dendritic cell activation, and T-cell lymphocyte stimulation. There are numerous major implications to study the microbiome in patients with benign and malignant hematologic disorders. In this review, we investigated the structure and function of the microbiome in patients with benign and malignant hematological diseases. Chemotherapy and immunosuppressive agents used in treatment of these benign and malignant hematological diseases may cause or exacerbate dysbiosis and infectious problems. After understanding the importance of microbiota in hematological diseases, we think that use of probiotics and dietary prebiotic substances targeting microbiota modification aiming to improve hematological disease outcomes should be investigated in future studies.

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Topics: Microbiome (63%), Dysbiosis (60%)

Open accessJournal ArticleDOI: 10.3390/CANCERS13194947
30 Sep 2021-Cancers
Abstract: For almost 30 years, the term "holobiont" has referred to an ecological unit where a host (e.g., human) and all species living in or around it are considered together. The concept highlights the complex interactions between the host and the other species, which, if disturbed may lead to disease and premature aging. Specifically, the impact of microbiome alterations on the etiology of acute lymphoblastic leukemia (ALL) in children is not fully understood, but has been the focus of much research in recent years. In ALL patients, significant reductions in microbiome diversity are already observable at disease onset. It remains unclear whether such alterations at diagnosis are etiologically linked with leukemogenesis or simply due to immunological alteration preceding ALL onset. Regardless, all chemotherapeutic treatment regimens severely affect the microbiome, accompanied by severe side effects, including mucositis, systemic inflammation, and infection. In particular, dominance of Enterococcaceae is predictive of infections during chemotherapy. Long-term dysbiosis, like depletion of Faecalibacterium, has been observed in ALL survivors. Modulation of the microbiome (e.g., by fecal microbiota transplant, probiotics, or prebiotics) is currently being researched for potential protective effects. Herein, we review the latest microbiome studies in pediatric ALL patients.

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Topics: Microbiome (64%), Oral Microbiome (62%), Premature aging (54%) ... show more
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92 results found


Open accessJournal ArticleDOI: 10.1038/NATURE08821
Junjie Qin1, Ruiqiang Li1, Jeroen Raes2, Manimozhiyan Arumugam  +49 moreInstitutions (5)
04 Mar 2010-Nature
Abstract: To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, ~150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively

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Topics: Metagenomics (60%), Bacterial genome size (53%), Genomics (52%) ... show more

7,873 Citations


Open accessJournal ArticleDOI: 10.1126/SCIENCE.7997879
Yuan Chang1, Ethel Cesarman1, Melissa S. Pessin1, Frank Lee  +3 moreInstitutions (2)
16 Dec 1994-Science
Abstract: Representational difference analysis was used to isolate unique sequences present in more than 90 percent of Kaposi's sarcoma (KS) tissues obtained from patients with acquired immunodeficiency syndrome (AIDS). These sequences were not present in tissue DNA from non-AIDS patients, but were present in 15 percent of non-KS tissue DNA samples from AIDS patients. The sequences are homologous to, but distinct from, capsid and tegument protein genes of the Gammaherpesvirinae, herpesvirus saimiri and Epstein-Barr virus. These KS-associated herpesvirus-like (KSHV) sequences appear to define a new human herpesvirus.

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Topics: Kaposi's sarcoma-associated herpesvirus (70%), Kaposi's sarcoma (66%), Gammaherpesvirinae (64%) ... show more

5,307 Citations


Open accessJournal ArticleDOI: 10.1038/NATURE06244
17 Oct 2007-Nature
Abstract: A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.

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Topics: Human Microbiome Project (66%), Microbiome (60%), Human microbiome (56%) ... show more

3,977 Citations


Open accessJournal ArticleDOI: 10.1126/SCIENCE.1124234
Steven R. Gill, Mihai Pop, Robert T. DeBoy, Paul B. Eckburg1  +8 moreInstitutions (4)
02 Jun 2006-Science
Abstract: The human intestinal microbiota is composed of 10(13) to 10(14) microorganisms whose collective genome ("microbiome") contains at least 100 times as many genes as our own genome. We analyzed approximately 78 million base pairs of unique DNA sequence and 2062 polymerase chain reaction-amplified 16S ribosomal DNA sequences obtained from the fecal DNAs of two healthy adults. Using metabolic function analyses of identified genes, we compared our human genome with the average content of previously sequenced microbial genomes. Our microbiome has significantly enriched metabolism of glycans, amino acids, and xenobiotics; methanogenesis; and 2-methyl-d-erythritol 4-phosphate pathway-mediated biosynthesis of vitamins and isoprenoids. Thus, humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes.

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Topics: Human Microbiome Project (65%), Microbiome (63%), Metagenomics (58%) ... show more

3,636 Citations


Open accessJournal ArticleDOI: 10.1038/NATURE11550
13 Sep 2012-Nature
Abstract: Trillions of microbes inhabit the human intestine, forming a complex ecological community that influences normal physiology and susceptibility to disease through its collective metabolic activities and host interactions. Understanding the factors that underlie changes in the composition and function of the gut microbiota will aid in the design of therapies that target it. This goal is formidable. The gut microbiota is immensely diverse, varies between individuals and can fluctuate over time — especially during disease and early development. Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.

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Topics: Gut flora (53%)

3,147 Citations


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