We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet, which we confirm with untargeted metabolomics on hundreds of samples.
SUMMARY BackgroundChemotherapy 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.
SUMMARY BackgroundGastrointestinal mucositis is defined as inflammation and/or ulcers of the gastrointestinal tract occurring as a complication of chemotherapy and radiation therapy, and affects about 50% of all cancer patients.
Bacteremia remains a major cause of life-threatening complication in patients with cancer. Significant changes in the spectrum of microorganisms isolated from blood culture have been reported in cancer patients over the past years. The aim of our systematic review was to inventory the recent trends in epidemiology and antibiotic resistance of microorganisms causing bacteremia in cancer patients. Data for this review was identified by searches of Medline, Scopus and Cochrane Library for indexed articles and abstracts published in English since 2008. The principal search terms were: "antimicrobial resistance", "bacteremia", "bacterial epidemiology", "bloodstream infection", "cancer patients", "carbapenem resistance", "Escherichia coli resistance", "extended-spectrum β-lactamase producing E. coli", "febrile neutropenia", "fluoroquinolone resistance", "neutropenic cancer patient", "vancomycin-resistant Enterococcus", and "multidrug resistance". Boolean operators (NOT, AND, OR) were also used in succession to narrow and widen the search. Altogether, 27 articles were selected to be analyzed in the review. We found that Gram-negative bacteria were the most frequent pathogen isolated, particularly in studies with minimal use of antibiotic prophylaxis. Another important trend is the extensive emergence of antimicrobial-resistant strains associated with increased risk of morbidity, mortality and cost. This increasing incidence of antibiotic resistance has been reported in Gram-negative bacteria as well as in Gram-positive bacteria. This exhaustive review, reporting the recent findings in epidemiology and antibiotic resistance of bacteremia in cancer patients, highlights the necessity of local continuous surveillance of bacteremia and stringent enforcement of antibiotic stewardship programs in cancer patients.
SummaryBackground: Global prescription drug use has been increasing continuously for decades.
word count: 203 68 3 Main text word count: 3280 69 70 Abstract: Although much work has linked the human microbiome to specific phenotypes and 71 lifestyle variables, data from different projects have been challenging to integrate and the extent 72 of microbial and molecular diversity in human stool remains unknown. Using standardized 73 protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-74 scientists, together with an open research network, we compare human microbiome specimens 75 primarily from the USA, UK, and Australia to one another and to environmental samples. Our 76 results show an unexpected range of beta-diversity in human stool microbiomes as compared to 77 environmental samples, demonstrate the utility of procedures for removing the effects of 78 overgrowth during room-temperature shipping for revealing phenotype correlations, uncover 79 new molecules and kinds of molecular communities in the human stool metabolome, and 80 examine emergent associations among the microbiome, metabolome, and the diversity of plants 81 that are consumed (rather than relying on reductive categorical variables such as veganism, 82 which have little or no explanatory power). We also demonstrate the utility of the living data 83 resource and cross-cohort comparison to confirm existing associations between the microbiome 84 and psychiatric illness, and to reveal the extent of microbiome change within one individual 85 during surgery, providing a paradigm for open microbiome research and education. 86 87Importance: We show that a citizen-science, self-selected cohort shipping samples through the 88 mail at room temperature recaptures many known microbiome results from clinically collected 89 cohorts and reveals new ones. Of particular interest is integrating n=1 study data with the 90 population data, showing that the extent of microbiome change after events such as surgery can 91 4 exceed differences between distinct environmental biomes, and the effect of diverse plants in the 92 diet which we confirm with untargeted metabolomics on hundreds of samples. 93 94 Introduction 95The human microbiome plays a fundamental role in human health and disease. While 96 many studies link microbiome composition to phenotypes, we lack understanding of the 97 boundaries of bacterial diversity within the human population, and the relative importance of 98 lifestyle, health conditions, and diet, to underpin precision medicine or to educate the broader 99 community about this key aspect of human health. 100 We launched the American Gut Project (AGP; http://americangut.org) in November of 101 2012 as a collaboration between the Earth Microbiome Project (EMP) (1) and the Human Food 102 Project (HFP; http://humanfoodproject.com/) to discover the kinds of microbes and microbiomes 103 "in the wild" via a self-selected citizen-scientist cohort. The EMP is tasked with characterizing 104 the global microbial taxonomic and functional diversity, and the HFP is focused on 105 understanding microbial diversity a...
BackgroundBacteremia, 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.MethodsWe sampled 28 patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic stem cell transplantation (HSCT) prior to administration of chemotherapy and characterized 16S ribosomal RNA genes using high-throughput DNA sequencing. We quantified bacterial taxa and used techniques from machine learning to identify microbial biomarkers that predicted subsequent BSI.ResultsWe found that patients who developed subsequent BSI exhibited decreased overall diversity and decreased abundance of taxa including Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella. Using machine-learning methods, we developed a BSI risk index capable of predicting BSI incidence with a sensitivity of 90 % at a specificity of 90 % based only on the pretreatment fecal microbiome.ConclusionsThese results suggest that the gut microbiota can identify high-risk patients before HSCT and that manipulation of the gut microbiota for prevention of BSI in high-risk patients may be a useful direction for future research. This approach may inspire the development of similar microbiome-based diagnostic and prognostic models in other diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0301-4) contains supplementary material, which is available to authorized users.
Gastrointestinal disturbances are a side-effect frequently associated with haematological malignancies due to the intensive cytotoxic treatment given in connection with bone marrow transplantation (BMT). However, intestinal microbiota changes during chemotherapy remain poorly described, probably due to the use of culture-based and low-resolution molecular methods in previous studies. The objective of our study was to apply a next generation DNA sequencing technology to analyse chemotherapy-induced changes in faecal microbiota. We included eight patients with non-Hodgkin's lymphoma undergoing one course of BMT conditioning chemotherapy. We collected a prechemotherapy faecal sample, the day before chemotherapy was initiated, and a postchemotherapy sample, collected 1 week after the initiation of chemotherapy. Total DNA was extracted from faecal samples, denaturing high-performance liquid chromatography based on amplification of the V6 to V8 region of the 16S ribosomal RNA (rRNA) gene, and 454-pyrosequencing of the 16 S rRNA gene, using PCR primers targeting the V5 and V6 hypervariable 16S rRNA gene regions were performed. Raw sequence data were screened, trimmed, and filtered using the QIIME pipeline. We observed a steep reduction in alpha diversity and significant differences in the composition of the intestinal microbiota in response to chemotherapy. Chemotherapy was associated with a drastic drop in Faecalibacterium and accompanied by an increase of Escherichia. The chemotherapy-induced shift in the intestinal microbiota could induce severe side effects in immunocompromised cancer patients. Our study is a first step in identifying patients at risk for gastrointestinal disturbances and to promote strategies to prevent this drastic shift in intestinal microbiota.
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