786 research outputs found

    Microbiome and colorectal cancer : Roles in carcinogenesis and clinical potential

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    Altres ajuts: Instituto Nacional de Bioinformatica (INB, grant PT17/0009/0023 - ISCIII-SGEFI/ERDF)The gastrointestinal tract harbors most of the microbiota associated with humans. In recent years, there has been a surge of interest in assessing the relationships between the gut microbiota and several gut alterations, including colorectal cancer. Changes in the gut microbiota in patients suffering colorectal cancer suggest a possible role of host-microbe interactions in the origin and development of this malignancy and, at the same time, open the door for novel ways of preventing, diagnosing, or treating this disease. In this review we survey current knowledge on the healthy microbiome of the gut and how it is altered in colorectal cancer and other related disease conditions. In describing past studies we will critically assess technical limitations of different approaches and point to existing challenges in microbiome research. We will have a special focus on host-microbiome interaction mechanisms that may be important to explain how dysbiosis can lead to chronic inflammation and drive processes that influence carcinogenesis and tumor progression in colon cancer. Finally, we will discuss the potential of recent developments of novel microbiota-based therapeutics and diagnostic tools for colorectal cancer

    Citizen-science reveals changes in the oral microbiome in Spain through age and lifestyle factors

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    The relevance of the human oral microbiome to our understanding of human health has grown in recent years as microbiome studies continue to develop. Given the links of the oral cavity with the digestive, respiratory and circulatory systems, the composition of the oral microbiome is relevant beyond just oral health, impacting systemic processes across the body. However, we still have a very limited understanding about intrinsic and extrinsic factors that shape the composition of the healthy oral microbiome. Here, we followed a citizen-science approach to assess the relative impact on the oral microbiome of selected biological, social, and lifestyle factors in 1648 Spanish individuals. We found that the oral microbiome changes across age, with middle ages showing a more homogeneous composition, and older ages showing more diverse microbiomes with increased representation of typically low abundance taxa. By measuring differences within and between groups of individuals sharing a given parameter, we were able to assess the relative impact of different factors in driving specific microbial compositions. Chronic health disorders present in the analyzed population were the most impactful factors, followed by smoking and the presence of yeasts in the oral cavity. Finally, we corroborate findings in the literature that relatives tend to have more similar oral microbiomes, and show for the first time a similar effect for classmates. Multiple intrinsic and extrinsic factors jointly shape the oral microbiome. Comparative analysis of metabarcoding data from a large sample set allows us to disentangle the individual effects.We are thankful to all citizens that participated in the second edition of the “Saca La Lengua” project by contributing samples and sharing ideas (see more details here www.sacalalengua.org). In particular, for the work described here we are extremely thankful to all the students and teachers of the schools that we have visited, for their enthusiasm and questions, which helped to expand our hypotheses, to those responsible for civic centers, libraries, museums, bars, for giving us their spaces and giving us the possibility of organizing all events, and to the following national associations: Spanish Federation of Cystic Fibrosis (www.fibrosisquistica.org), Down España (www.sindromedown.net), and Federación de Asociaciones de Celíacos de España (www.celiacos.org); and local associations: Asociación Madrileña de Fibrosis Quística, Associació Catalana de Fibrosi Quística, Cocemfe Cantabria, Down Lleida, Down Bilbao, Down Vigo, Down Málaga, Associació Celíacs de Catalunya, Celíacos Euskadi, Federación de Asociaciones Celíacos Andalucía, and Asojum Murcia. Only with their effort are studies like this possible. The authors acknowledge the CRG Genomics Core Facility, CRG Bioinformatics Core Facility, CRG Biomolecular Screening and Protein Technologies Unit, CRG Communication and Public Relationships Department, and UCT ICTS High Performance Computing unit for providing access to the computing facilities. CRG authors acknowledge the Spanish Ministry for Economy, Industry and Competitiveness (MEIC) for the EMBL partnership, and Centro de Excelencia Severo Ochoa. The following reagents were obtained through BEI Resources, NIAID, NIH as part of the Human Microbiome Project: (1) Genomic DNA from Microbial Mock Community B (Even, Low Concentration), v5.1 L, for 16 S rRNA Gene Sequencing, HM-782D, and (2) Genomic DNA from Microbial Mock Community B (Staggered, Low Concentration), v5.2 L, for 16 S rRNA Gene Sequencing, HM-783D. The project was financed by the CRG through Genomics and Bioinformatics Core Facilities funds, and by the EduCaixa program through funds from the Fundación Bancaria “La Caixa”, with the participation of the Center for Research into Environmental Epidemiology (CREAL), and the “Centre d’Excellència Severo Ochoa 2013–2017” program (SEV-2012-02-08) of the Ministry of Economy and Competitiveness. Eppendorf, Illumina, and ThermoFisher sponsored the research by donating some materials and reagents. TG group acknowledges support from the Spanish Ministry of Science and Innovation for grant PGC2018-099921-B-I00, cofounded by European Regional Development Fund (ERDF); from the CERCA Program / Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR423; from the European Union’s Horizon 2020 research and innovation program under the grant agreement ERC-2016-724173; from Instituto de Salud Carlos III (INB Grant PT17/0009/0023 - ISCIII-SGEFI/ERDF).Peer Reviewed"Article signat per 15 autors/es: Jesse R. Willis, Ester Saus, Susana Iraola-Guzmán, Ewa Ksiezopolska, Luca Cozzuto, Luis A. Bejarano, Nuria Andreu-Somavilla, Miriam Alloza-Trabado, Andrea Blanco, Anna Puig-Sola, Elisabetta Broglio, Carlo Carolis, Julia Ponomarenko, Jochen Hecht & Toni Gabaldón"Postprint (published version

    Coral-associated bacteria demonstrate phylosymbiosis and cophylogeny

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    Scleractinian corals' microbial symbionts influence host health, yet how coral microbiomes assembled over evolution is not well understood. We survey bacterial and archaeal communities in phylogenetically diverse Australian corals representing more than 425 million years of diversification. We show that coral microbiomes are anatomically compartmentalized in both modern microbial ecology and evolutionary assembly. Coral mucus, tissue, and skeleton microbiomes differ in microbial community composition, richness, and response to host vs. environmental drivers. We also find evidence of coral-microbe phylosymbiosis, in which coral microbiome composition and richness reflect coral phylogeny. Surprisingly, the coral skeleton represents the most biodiverse coral microbiome, and also shows the strongest evidence of phylosymbiosis. Interactions between bacterial and coral phylogeny significantly influence the abundance of four groups of bacteria-including Endozoicomonas-like bacteria, which divide into host-generalist and host-specific subclades. Together these results trace microbial symbiosis across anatomy during the evolution of a basal animal lineage

    Determining population structure among Argentinian jaguars (Panthera onca)

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    The jaguar (Panthera onca) is the largest felid in America and the most emblematic South American predator. This carnivore species holds a high environmental importance in all ecosystems it inhabits for its apex predator role. Jaguar populations have suffered an important decline over the last century and today this species is considered as critically endangered in Argentina. Ensuring the sustainability of theremaining jaguar populations demands a high degree of knowledge about the current state of their genetic variability levels and a description of population structure is essential, especially to allow rational translocation and reintroduction actions. The first jaguar reference genome was released in2017 (Figueiro et al. 2017) by the Jaguar Genome Project, a consortium we integrate.With the aim of generating useful resources and information for the jaguar genetics and conservation from the genomic perspective, we carried out the whole genome sequencing of 9 jaguar samples using Illumina 2500 NSG technology. Here we present the first results obtained from these 9 genomescompared to the reference. We performed a population structure analysis in order to estimate the optimal number of populations present in our data and a Multiple Correspondece Analysis (MCA) clustering of our samples based on over 280.000 homozygous variable positions in their genomes. Theestimation of the optimal number of populations present among our samples resulted in 6, according to the Structure analysis. However, the MCA clustering analysis only revealed 5 groups of individuals. The main genetic cluster of animal obtained is integrated by captive animals from zoos and natural reserves and surprisingly a Paraguayan male. Apart from this central group, a wild Argentinian sample from Misiones (a province in the north-east of the country) was located. Also, an animal of Uruguayan origin and the reference, built from a Brazilian animal, located in individual clusters.More work including heterozygous variable position analysis will be performed to better describe the genetic variability among the sequenced jaguar genomes and accurately describe the current genetic situation and population structure of this species in Argentinian territory.Fil: Pisciottano, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Tarifa Reischle, Inti Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pegueroles Queralt, Cinta. Centro de Regulación Genómica; España. Universitat Pompeu Fabra; EspañaFil: Willis, Jesse R.. Centro de Regulación Genómica; EspañaFil: Julca Chavez, Irene Consuelo. Centro de Regulación Genómica; España. Universitat Pompeu Fabra; EspañaFil: Gabaldón, Toni. Centro de Regulación Genómica; España. Institució Catalana de Recerca i Estudis Avançats ; EspañaFil: Saragueta, Patricia Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaExploring Genomic Landscapes EMBO WorkshopSan Pedro de AtacamaChileEMBOCenter for Genomic Regulatio

    Microbiome Profiling from Fecal Immunochemical Test Reveals Microbial Signatures with Potential for Colorectal Cancer Screening

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    Simple Summary Colorectal cancer (CRC) is a global healthcare challenge that involves both genetic and environmental factors. Several pieces of evidence suggest that alterations of the gut microbiome can influence CRC development. In the present study we analyzed 16S rRNA sequencing data from fecal immunochemical test (FIT) samples from a large cohort, observing a predictive potential of the microbiome, revealing changes along the path from healthy tissue to carcinoma. Our work has implications in the understanding of the roles of microbes on the adenoma to carcinoma progression and opens the door to an improvement of the current CRC screening programmes. Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer deaths worldwide. Early diagnosis of CRC, which saves lives and enables better outcomes, is generally implemented through a two-step population screening approach based on the use of Fecal Immunochemical Test (FIT) followed by colonoscopy if the test is positive. However, the FIT step has a high false positive rate, and there is a need for new predictive biomarkers to better prioritize cases for colonoscopy. Here we used 16S rRNA metabarcoding from FIT positive samples to uncover microbial taxa, taxon co-occurrence and metabolic features significantly associated with different colonoscopy outcomes, underscoring a predictive potential and revealing changes along the path from healthy tissue to carcinoma. Finally, we used machine learning to develop a two-phase classifier which reduces the current false positive rate while maximizing the inclusion of CRC and clinically relevant samples

    Phenotypic Variability in a Coinfection With Three Independent Candida parapsilosis Lineages

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    The human pathogenic yeastCandida parapsilosishas gained significant importance over the past decades as one of the principal causes of fungal bloodstream infections. Isolates ofC. parapsilosisare known to be able to switch between several different colony morphologies in vitro, which are correlated with different cell shapes, altered cell surface properties, and thus different capacities to form biofilms on indwelling medical devices. In a set of six clinical specimens from a single surgery patient yielding stable smooth- as well as crepe-morphology isolates, we investigated the differences between five of them on a phenotypic and genomic level. In contrast to the initial assumption that they were switched forms of a clonal strain, karyotyping and genome sequencing showed that the patient was colonized by at least three distinct linages. Statistical analysis placed these groups distantly across the population ofC. parapsilosis. Interestingly the single blood culture isolate was of smooth morphology and matched with an isolate from the patient's nose of similar morphology. Strong variation between the isolates was seen in adhesin-encoding genes, where repeat regions showed significant variation in length and repeat-numbers, most strikingly inHWP1of the smooth isolates. Although no differences in drug susceptibility were evident, the high phylogenetic distance separating the individual strains highlights the need for testing of multiple colonies in routine practice. The absence of biofilm formation in the blood stream isolate indicates a lack of respective adhesins in the cell wall, in turn pointing toward lack of adhesion as a positively contributing factor for dissemination

    Changes in the stool and oropharyngeal microbiome in obsessive-compulsive disorder

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    Although the etiology of obsessive-compulsive disorder (OCD) is largely unknown, it is accepted that OCD is a complex disorder. There is a known bi-directional interaction between the gut microbiome and brain activity. Several authors have reported associations between changes in gut microbiota and neuropsychiatric disorders, including depression or autism. Furthermore, a pediatric-onset neuropsychiatric OCD-related syndrome occurs after streptococcal infection, which might indicate that exposure to certain microbes could be involved in OCD susceptibility. However, only one study has investigated the microbiome of OCD patients to date. We performed 16S ribosomal RNA gene-based metagenomic sequencing to analyze the stool and oropharyngeal microbiome composition of 32 OCD cases and 32 age and gender matched controls. We estimated different α- and β-diversity measures and performed LEfSe and Wilcoxon tests to assess differences in bacterial distribution. OCD stool samples showed a trend towards lower bacterial α-diversity, as well as an increase of the relative abundance of Rikenellaceae, particularly of the genus Alistipes, and lower relative abundance of Prevotellaceae, and two genera within the Lachnospiraceae: Agathobacer and Coprococcus. However, we did not observe a different Bacteroidetes to Firmicutes ratio between OCD cases and controls. Analysis of the oropharyngeal microbiome composition showed a lower Fusobacteria to Actinobacteria ratio in OCD cases. In conclusion, we observed an imbalance in the gut and oropharyngeal microbiomes of OCD cases, including, in stool, an increase of bacteria from the Rikenellaceae family, associated with gut inflammation, and a decrease of bacteria from the Coprococcus genus, associated with DOPAC synthesis

    Copper Chaperone for Cu/Zn Superoxide Dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc

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    BACKGROUND: Small increases in zinc (Zn) consumption above recommended amounts have been shown to reduce copper (Cu) status in experimental animals and humans. Recently, we have reported that copper chaperone for Cu/Zn superoxide dismutase (CCS) protein level is increased in tissues of overtly Cu-deficient rats and proposed CCS as a novel biomarker of Cu status. METHODS: Weanling male Wistar rats were fed one of four diets normal in Cu and containing normal (30 mg Zn/kg diet) or moderately high (60, 120 or 240 mg Zn/kg diet) amounts of Zn for 5 weeks. To begin to examine the clinical relevance of CCS, we compared the sensitivity of CCS to mild Cu deficiency, induced by moderately high intakes of Zn, with conventional indices of Cu status. RESULTS: Liver and erythrocyte CCS expression was significantly (P < 0.05) increased in rats fed the Zn-60 and/or Zn-120 diet compared to rats fed normal levels of Zn (Zn-30). Erythrocyte CCS expression was the most sensitive measure of reduced Cu status and was able to detect a decrease in Cu nutriture in rats fed only twice the recommended amount of Zn. Liver, erythrocyte and white blood cell CCS expression showed a significant (P < 0.05) inverse correlation with plasma and liver Cu concentrations and caeruloplasmin activity. Unexpectedly, rats fed the highest level of Zn (Zn-240) showed overall better Cu status than rats fed a lower level of elevated Zn (Zn-120). Improved Cu status in these rats correlated with increased duodenal mRNA expression of several Zn-trafficking proteins (i.e. MT-1, ZnT-1, ZnT-2 and ZnT-4). CONCLUSION: Collectively, these data show that CCS is a sensitive measure of Zn-induced mild Cu deficiency and demonstrate a dose-dependent biphasic response for reduced Cu status by moderately high intakes of Zn

    Comparing the use of meat and clay during cutting and projectile research

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    Diverse disciplines investigate how muscular tissue (i.e. ‘meat’) responds to being cut and deformed, however, large-scale, empirically robust investigations into these matters are often impractical and expensive. Previous research has used clay as an alternative to meat. To establish whether clay is a reliable proxy for meat, we directly compare the two materials via a series of cutting and projectile tests. Results confirm that the two materials display distinct cutting mechanics, resistance to penetration and are not comparable. Under certain conditions clay can be used as an alternative to meat, although distinctions between the two may lead to experimental limitations
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