the integrative human microbiome project

Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Finally, each HMP2 study was necessarily carried out within a geographically and genetically constrained population, and global differences in early life events, infectious disease exposure, or diet may change how microbiome dynamics contribute to human disease. Molina MA, Andralojc KM, Huynen MA, Leenders WPJ, Melchers WJG. The Human Microbiome Project. FASEB J. From each patient in every visit, blood sample and microbiome sample (including nasal swabs and stool and urine samples) are collected. The unique immunological and microbial aspects of pregnancy. Franzosa EA, et al. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Stappenbeck TS, Wong MH, Saam JR, Mysorekar IU, Gordon JI. Gastroenterology 139, 18441854.e1841 (2010). A longitudinal big data approach for precision health. PubMed February 12, 2018 - National Advisory Council for Human Genome Research (Open Session). Protocols and results from the study, further information about its infrastructure, and both raw and processed76,77 data products are available through the IBDMDB data portal (http://ibdmdb.org), from the HMP2 Data Coordination Center (DCC; http://ihmpdcc.org), and in the accompanying manuscript49. We acknowledge funding from NIH grants UH2/UH3AI083263 and U54HD080784 (G.A.B., J.F.S., K. Jefferson) supported with funds from the Common Fund, the National Center for Complementary and Integrative Health, and the Office of Research on Womens Health, grant U54DK102557 (C.H., R. Xavier), including funds from the Common Fund, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Complementary and Integrative Health, and the Office of Dietary Supplements and grant U54DK102556 (M.P.S., G.M.W. Ananthakrishnan AN, Huang H, Nguyen DD, Sauk J, Yajnik V, Xavier RJ. Strains, functions and dynamics in the expanded Human Microbiome Project. Differences in vaginal microbiome in African American women versus women of European ancestry. Google Scholar. Sci. The vaginal microbiota of pregnant women who subsequently have spontaneous preterm labor and delivery and those with a normal delivery at term. Type 2 diabetes mellitus (T2D) affects more than 10% of the adult US population, and another 30% show early signs of the disease (referred to as prediabetes)80; 70% of the latter will develop diabetes in their lifetime. See this image and copyright information in PMC. Recruit well-characterized subjects within these three cohorts targeting, respectively, new-onset pediatric subjects, new-onset adult subjects, and established Crohns disease and ulcerative colitis, in addition to non-IBD controls. Erickson, A. R. et al. 2013;9:286293. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women. Copyright 2014 The Authors. IMG/M-HMP: a metagenome comparative analysis system for the Human Microbiome Project. Longitudinal multi-omics of hostmicrobe dynamics in prediabetes. sharing sensitive information, make sure youre on a federal These efforts revealed the vast microbial diversity associated with humans and provided new insights into the ecology of the host-microbiome supraorganism (Human Microbiome Project Consortium, 2012a, 2012b). Meanwhile, specific changes in the microbiome of the vaginal lumen can be associated with preterm birth, possibly through mechanisms involving microorganisms travelling from the vagina to the uterus. These projects included three studies that followed the dynamics of human health and disease during conditions with known microbiome interactions, thus addressing important health outcomes directly while also serving as models of typical microbiome-associated conditions of broad interest to the research community. Cell Syst. From the HMP2, these include data that IRBs gave permission to be made publicly available from the pregnancy and preterm birth (MOMS-PI), inflammatory bowel disease (IBDMDB), and prediabetes (IPOP) projects, with links to raw data in other repositories. M.S. PubMed Samples from Crohns disease patients, ulcerative colitis patients, and non-IBD controls are collected at Massachusetts General Hospital (adult new onset), Emory University (pediatric new onset), Cincinnati Childrens Hospital (pediatric new onset), and Cedars-Sinai Medical Center (adult established). This site needs JavaScript to work properly. Data produced by the iHMP Consortium will be routinely released, and ongoing feedback is encouraged on how best to leverage these resources. Natl Acad. Med. Gregory A. Buck, Michael P. Snyder, Jerome F. Strauss III, George M. Weinstock, Owen White or Curtis Huttenhower. This study includes a viral enrichment and sequencing protocol for each stool sample. Overall, the data led to microbially linked, clinically actionable health discoveries in a number of diseases in addition to T2D, including metabolic disease, cardiovascular disease, haematological or oncological conditions, and other areas; these signs were often present before symptom onset, demonstrating the power of using big data, including the microbiome, to better manage human health. Infant mortality has been reduced in recent decades, but the incidence of PTB has not decreased54, and progress in predicting individual risk of PTB has stalled. 2012;8:e1002358. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Natl Acad. Ravel, J. et al. The annual United States health care costs for newborns with complications exceeds $26 billion (Behrman and Butler, 2007). Althoughthe overall MOMS-PI cohort was demographically diverse, most women who experienced spontaneous PTB at less than 37 weeks of gestation were of African ancestry. NIH Human Microbiome Portfolio Analysis Team A review of 10years of human microbiome research activities at the US National Institutes of Health, Fiscal Years 20072016. This marker paper outlines the second phase of HMP, the Integrative Human Microbiome Project (iHMP), which will examine the role of the microbiome in human health and disease through a study of three models of microbiome-related conditions. Multiple sample types will be collected from the study participants every 23 months during their healthy periods, with more frequent sampling during periods of respiratory illness and other environmental stress. Multi-omic data generation (primarily, but not entirely, nucleotide sequence- and mass spectroscopy-based) provides microbial, host, and mixed profiles including 16S rRNA gene surveys, whole metagenome and metatranscriptome shotgun sequences, metabolite and protein profiles, single-cell assays, whole virome shotgun sequences, and serological profiles. A review of 10years of human microbiome research activities at the US National Institutes of Health, Fiscal Years 20072016. Another notable property was that, as in most microbiome studies, changes that occurred within individuals, populations, or phenotypes were often much smaller than baseline variation between individuals. To gain insight into the breadth of metabolic changes that occur, untargeted metabolomics profiling of urine and plasma samples will be performed using an optimized LC-MS procedure (liquid chromatography coupled to mass spectrometry). Succession of microbial consortia in the developing infant gut microbiome. Science 359, 104108 (2018). The MOMS-PI project followed 1,527 pregnancies longitudinally and involved the collection of 206,437 biospecimens for analysis of host and microbial factors (16S amplicon, metagenomic, and metatranscriptomic sequencing; cytokine profiling; metabolomics; proteomics; genomics; and microbial isolate culture). Science 312, 13551359 (2006). Schirmer, M. et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Bacterial community variation in human body habitats across space and time. These include whole metagenome shotgun and metatranscriptome sequencing, host whole genome/transcriptome sequencing, cytokine and autoantibody profiles, metabolomics profiles, and standard clinical tests (Figure 3). Cowie, C. C. et al. Functional profile of host microbiome indicates. ; toddler swing set how to download dropbox files without permission; condense nogaps in sap abap Microbiome Labs. Multi-omic data generation (primarily, but not entirely, nucleotide sequence- and mass spectroscopy-based) will provide profiles of microbial phylogenetic composition, metagenomes, metatranscriptomes, and metaproteomes; host protein profiles, cytokines, and autoantibodies; and global metabolome profiles. A list of participants and their affiliations appears at the end of the paper. Measure of metabolomic profiles using untargeted and targeted LC-MS methods. Dominguez-Bello MG, et al. This unique study design allowed the IBDMDB to identify a variety of differences in the microbiome and host immune response over time during the course of the disease. The other authors declare no competing interests. The HMP1 focused on the characterization of microbial communities from numerous body sites (oral, nasal, vaginal, gut, and skin) in a baseline study of healthy adult subjects, and included a set of demonstration projects that focused on specific diseases or disorders. The figure depicts an overview of longitudinal changes in the vaginal mucosal ecosystem and uterus during pregnancy. Analysis of the gut microbiota in the old order Amish and its relation to the metabolic syndrome. Extensive unexplored human microbiome diversity revealed by over 150,000 genomes from metagenomes spanning age, geography, and lifestyle. A framework for human microbiome research. Nature 569, 641648 (2019). To the extent possible, multiple molecular profiles were generated from the same sets of samples, including stool metagenomes, metatranscriptomes73, metaproteomes, viromes, metabolomes74,75, host exomes, epigenomes, transcriptomes, and serological profiles, among others, allowing concurrent changes to be observed in multiple types of host and microbial molecular and clinical activity over time. 2015-04 DS Bae Genome-wide characterization of the routes to pluripotency . Nature https://doi.org/10.1038/s41586-019-1237-9 (2019). Natl Acad. From each patient in every visit, blood sample and microbiome sample (including nasal swabs and stool and urine samples) are collected. A core human microbiome as viewed through 16S rRNA sequence clusters. Gevers D, Knight R, Petrosino JF, Huang K, McGuire AL, Birren BW, Nelson KE, White O, Meth BA, Huttenhower C. The Human Microbiome Project: a community resource for the healthy human microbiome. Nature 486, 207214 (2012). Schloissnig S, et al. T2D is characterized by complex hostmicrobiome interactions81,82, but little is known about systemic alterations during prediabetes, their effects on biological processes, or the critical transition to full-blown T2D. Disease-targeted projects within theHMP2 were therefore encouraged to use multiple complementary approaches in order to assess the mechanisms of human and microbial activity longitudinally and to provide protocols, data, and biospecimens for future work. Federal government websites often end in .gov or .mil. Two phases of the HMP (HMP and iHMP) together generated >48TB of data (public and controlled access) from multiple, varied omics studies of both the microbiome and associated hosts. The other authors declare no competing interests. Resources from HMP1 and HMP2 available at the DCC. The MOMS-PI project followed 1,527 pregnancies longitudinally and involved the collection of 206,437 biospecimens for analysis of host and microbial factors (16S amplicon, metagenomic, and metatranscriptomic sequencing; cytokine profiling; metabolomics; proteomics; genomics; and microbial isolate culture). Additional data deposited elsewhere including microbial reference genomes, HMP1 human genomes, and controlled access data for all HMP2 projects is also linked from the DCC. With the addition of new data from the microbiome, other environmental factors, and multi-omic inputs, new algorithms promise to improve our ability to predict risk of PTB early in pregnancy, to facilitate clinical trials by identifying high-risk patients, and ultimately to stratify patient populations into treatment groups. Before Schloissnig, S. et al. The HMP DCC efforts are thus by design consistent with the NIHs stated goals to make all data generated from NIH funding findable, accessible, interoperable, and reusable88. (T2D); H.H.C., A.M. and O.W. Sci. Preterm Birth: Causes, Consequences, and Prevention (National Academies Press, 2007). A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. VEBA: a modular end-to-end suite for in silico recovery, clustering, and analysis of prokaryotic, microeukaryotic, and viral genomes from metagenomes, In-depth insights into cervicovaginal microbial communities and hrHPV infections using high-resolution microbiome profiling, Effect of invasive mechanical ventilation on the diversity of the pulmonary microbiota, Microbial risk score for capturing microbial characteristics, integrating multi-omics data, and predicting disease risk, Phylogeny-guided microbiome OTU-specific association test (POST), Gut microbiome responses to dietary intervention with hypocholesterolemic vegetable oils, AGAMEMNON: an Accurate metaGenomics And MEtatranscriptoMics quaNtificatiON analysis suite, Loss of NFE2L3 protects against inflammation-induced colorectal cancer through modulation of the tumor microenvironment, The role of the microbiota in the management of intensive care patients, The Integrative HMP (iHMP) Research Network Consortium, https://www.hmpdacc.org/health/projectdemos.php, https://www.nature.com/collections/fiabfcjbfj, https://www.niaid.nih.gov/research/trans-nih-microbiome-working-group, https://commonfund.nih.gov/hmp/programhighlights, https://doi.org/10.1038/s41586-019-1237-9, https://doi.org/10.1038/s41591-019-0450-2, https://doi.org/10.1038/s41586-019-1236-x, https://doi.org/10.1038/s41591-019-0465-8, https://doi.org/10.1038/s41372-019-0343-8, http://creativecommons.org/licenses/by/4.0/, Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases, Longitudinal multi-omics of hostmicrobe dynamics in prediabetes, Racioethnic diversity in the dynamics of the vaginal microbiome during pregnancy. As pregnancy progresses, with predictable changes in systemic oestradiol levels, the uterine and vaginal environments undergo various changes. 2007;4:25932602. Fine-mapping inflammatory bowel disease loci to single-variant resolution. Ords I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. The relative contributions of fetal and maternal genetics and epigenetics, particularly as related to genetic variation of the innate immune system, should be explored. about navigating our updated article layout. Metagenomic analysis of the human distal gut microbiome. Bioinformatics 34, 12351237 (2018). Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. From the HMP1, these include 16S rRNA gene amplicons and metagenomes from the healthy human subjects (HHS) baseline cohort, as well as resources from demonstration projects (https://www.hmpdacc.org/health/projectdemos.php) and genomes of associated microbial isolates. Epidemiology and model systems have been used to identify associations between changes in the microbiome and conditions ranging from autism4 to cancer5,6,7, and microbial and immunological mechanisms have been identified that affect, for example, the efficacy of drugs used to treat cardiac conditions8 or survival during graft-versus-host disease9. (IBD); W.Z., M.P.S. Much has been learned about the diversity and distribution of human-associated microbial communities, but we still know little about the biology of the microbiome, how it interacts with the host, and how the host responds to its resident microbiota. As part of the Integrative Human Microbiome Project, these long-term studies help provide a framework for continuing investigations that seek to better understand the role of the human microbiomethe trillions of microorganisms that inhabit our bodiesand how changes in the microbiome are associated with, or even cause, illnesses. All sequences and multi-omic data, clinical information, and tools from both HMP1 and HMP2 are housed in the HMP Data Coordination Center (DCC) or referenced public or controlled-access repositories to serve as a central resource for the research community. Faust, K. et al. Broad researchers are now involved in phase two of HMP, the Integrative Human Microbiome Project (iHMP), where they lead a multi-institutional effort to understand how the human gut microbiome changes over time in adults and children with IBD. Hooper LV, Gordon JI. Google Scholar. This was due in part to the prospective nature of the cohort, which recruited patients with Crohns disease or ulcerative colitis during both active and quiescent periods of disease, showing that microbial compositions inpatients with IBD often revert to more control-like, baseline configurations when the disease is not active. Ratner RE, Diabetes Prevention Program Research An update on the Diabetes Prevention Program. 2017; Integrative HMP (iHMP) Research Network Consortium 2014 ). Each sample is further accompanied by clinical (blood) or self-reported stress level, environmental, and dietary (stool and urine) metadata. Google Scholar. Science. Thus, we plan to analyze levels of more than 150 lipids (e.g., eicosanoids, sphingolipids, and steroid hormones) in vaginal samples collected longitudinally throughout pregnancy using methods previously described (Wijesinghe et al., 2010, 2011). The PennCHOP Microbiome Program is a collaboration between the University of . To further characterize the microbiotas mechanisms of host interaction, profiles of host genetic and functional properties from a subset of longitudinal time points will also be collected. Strategies for metagenomic-guided whole-community proteomics of complex microbial environments. Cell Host Microbe 15, 382392 (2014). Although meta-omic techniques have been used to identify functionally consistent microbial responses that help to explain the gut microbiomes role as part of a pro-inflammatory feedback loop in the gut during disease71, and a few strains of microorganisms have been shown to be IBD-specific72, no comprehensive model of specific microbial, molecular, and immune interactions yet exists to explain the diseases onset and dynamic progression. Please enable it to take advantage of the complete set of features! In 2007. Cell. Relationship between vitamin D status and the vaginal microbiome during pregnancy. Lloyd-Price J, et al. Conversely, genetic variants were generally difficult to link to the microbiome in such small populations, which were necessary in order to deeply profile multi-omics over time, and we anticipate host sequencing to be more useful when integrated into larger cross-sectional surveys. Transl. Although each of the three HMP2 studies revealed new biology within their respective areas of health and disease, a surprising range of hostmicrobiome immune and ecological features were common among them. Categories of data are colour coded, and the number of items in each dataset is indicated by the size of the circles. Contemporary studies of the human microbiome have also been a source of basic biological and translational surprises, exposing a compelling range of novel findings and open questions. A multi-omic approach will probe properties of the host and microbial communities to generate an integrative, longitudinal, and comprehensive data set of 16S rRNA gene surveys, mass spectrometry-based lipidomic profiles, and cytokine assays. doi: 10.1093/gigascience/giac073. The program received $170 million in funding by the NIH Common Fund from 2007 to 2016. Microbiome in parturition and preterm birth. Launched in 2007 20, the first phase of the program sought to determine whether there were common elements to 'healthy' microbiomes, in the absence of overt disease. Fig. Prediabetes and T2D are often associated with insulin resistance, and thus studies of individuals with prediabetes or insulin resistance offer unique opportunities to investigate the earliest stages of diabetes. It is essential to create a global and simultaneous profile of both host and microbial molecules in individuals with prediabetes over time, in order to fully understand the molecular pathways that are affected in people with prediabetes and/or insulin resistance and how these conditions affect both biological responses to environmental challenges (for example, viral infections83,84) and the onset of T2D. Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, Cosnes J, Corthier G, Marteau P, Dor J. Analyses will be performed on early data sets from each of the projects; derived data sets used in these analyses will be made available at publication. Full accounting of diabetes and pre-diabetes in the U.S. population in 19881994 and 20052006. Studies of targeted populations identified ecological states of niches such as the vagina24,25, skin26,27,28, and gut29,30,31,32,33, among many others (https://www.hmpdacc.org/health/projectdemos.php). Diversity of the human intestinal microbial flora. The ten-year NIH Human Microbiome Project (HMP) program, organized into two phases (HMP1 and HMP2), developed reference sequences, multi-omic data sets, computational and statistical tools, and analytical and clinical protocols as resources for the broader research community. Sequence-based analysis of all genes in total DNA extracts; the data are used to develop microbial community compositional, functional, and genomic profiles. Ravel J, et al. The samples described above will be collected from (1) PRISM (the Prospective Registry in IBD Study at MGH), recruiting from Massachusetts General Hospital (Ananthakrishnan et al., 2014; Morgan et al., 2012); (2) the MLI (Mucosal Luminal Interface) cohort recruiting from Cedars-Sinai Medical Center (McHardy et al., 2013; Tong et al., 2013); and (3) a pediatric IBD cohort recruiting from Emory University and Cincinnati Childrens Hospital (Gevers et al., 2014; Walters et al., 2014). . In all three conditions, microbial changes and associated host responses were strongest when captured at the time the changes occurred, and often within the tissue of origin. Systematic review and meta-analysis: fecal microbiota transplantation for treatment of active ulcerative colitis. An official website of the United States government. Microbiome 7, 31 (2019). Bacterial RNA will be isolated and enriched for mRNA using procedures that remove > 95% of 16S and 23S rRNAs (Maurice et al., 2013; Turnbaugh et al., 2009). Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Human Microbiome Project Consortium A framework for human microbiome research. As a result, other aspects of hostmicrobiome interactions were highly localized and subject-specific within each of the three studies. Every human being appears to carry their own, largely individual, suite of microbial strains10,11, which are acquired early in life1214, differ between environments and populations15,16, and can persist for years17 or undergo relatively rapid transitions18. The MS data will be acquired using high-sensitivity, high-resolution mass spectrometers. PLoS One 7, e43052 (2012). Harmonized large-scale studies would permit the development of population-specific risk assessment algorithms using vaginal microbiome profiles, features from genetic and prenatal (fetal) genetic screens, biomarkers such as cytokines and metabolites, and key clinical features from classic markers of risk including maternal age, body mass index, pregnancy history (including history of PTB), cervical length, and measures of stress and other environmental exposures. (T2D); H.H.C., A.M. and O.W. Perform multi-omics analyses on maternal and neonatal samples. Erickson AR, et al. Analysis of bacterial bowel communities of IBD patients: what has it revealed? Liu L, et al. USA 111, 1252212527 (2014). Genetics and pathogenesis of inflammatory bowel disease. Study with repositories for the Primary data, and download data from and Among millions of measurements per individual over time, with only some changing. 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