Dirk Gevers

Dirk Gevers
  • Ph.D.
  • Broad Institute of MIT and Harvard

About

375
Publications
78,480
Reads
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73,793
Citations
Current institution
Broad Institute of MIT and Harvard
Additional affiliations
October 2010 - present
Broad Institute of MIT and Harvard
Position
  • Group Leader in Microbial Systems & Communities
Description
  • Together with his colleagues and collaborators, he is taking on several projects that bring together advanced sequence-based technologies and novel bioinformatic tools to characterize the vast complexity of the human microbiome in both health and disease.
April 2008 - October 2010
Broad Institute of MIT and Harvard
Position
  • Computational Biologist on the Human Microbiome Project
Description
  • Computational Biologist at the Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA, USA : 'The Human Microbiome Project'.
June 2006 - March 2008
Massachusetts Institute of Technology
Position
  • PostDoc Position
Description
  • Visiting postdoc at the Polz Lab, Civil & Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA: 'A population-level analysis of the bacterial species' (FWO travel grant).

Publications

Publications (375)
Preprint
Full-text available
To identify causal links between gut microbes and tumorigenesis, we colonized groups of germ-free colon tumor-susceptible mice ( Apc Min/+ ; Il10 −/− ) with 15 cultured human fecal microbiotas from healthy individuals, as well as patients with inflammatory bowel disease and colorectal cancer. The number of colonic tumors in Apc Min/+ ; Il10 −/− mic...
Preprint
Full-text available
We examine disease-specific and cross-disease functions of the human gut microbiome by colonizing germ-free mice, at risk for inflammatory arthritis, colitis, or neuroinflammation, with over 100 human fecal microbiomes from subjects with rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, ulcerative colitis, Crohn's disease, or colore...
Article
Full-text available
Fecal microbiota transplantation (FMT) has been successfully applied to treat recurrent Clostridium difficile infection in humans, but a precise method to measure which bacterial strains stably engraft in recipients and evaluate their association with clinical outcomes is lacking. We assembled a collection of >1,000 different bacterial strains that...
Article
Full-text available
The human microbiome, described as an accessory organ because of the crucial functions it provides, is composed of species that are uniquely found in humans1,2. Yet, surprisingly little is known about the impact of routine interpersonal contacts in shaping microbiome composition. In a relatively ‘closed’ cohort of 287 people from the Fiji Islands,...
Preprint
Full-text available
The human microbiome, described as an accessory organ because of the crucial functions it provides, is composed of species that are uniquely found in humans. Yet, surprisingly little is known about the impact of routine interpersonal contacts in shaping microbiome composition. In a relatively 'closed' cohort of 287 people from the Fiji Islands, whe...
Article
Full-text available
Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors¹, including complex genetic elements², patient exposures³ and the gut microbiome⁴. Viral infections⁵ and broader gut dysbioses⁶ have been identified as potential causes or contributing factors; however, human st...
Preprint
Full-text available
To examine the functional contribution of Inflammatory Bowel Disease (IBD) microbes to immune homeostasis and colitis, we colonized unchallenged and colitis-susceptible germ-free mice with over twenty human intestinal microbiotas from healthy and IBD donors. Compared to healthy microbiotas, IBD microbiotas led to expanded RORγt ⁺ Th17 cells and red...
Article
The classroom microbiome is different from the home microbiome. Higher classroom microbial diversity is associated with increased asthma symptoms. In this pilot study, a school-level integrated pest management intervention changed the classroom microbiome.
Article
Fecal microbiota transplantation (FMT) from healthy donor to patient is a treatment for microbiome-associated diseases. Although the success of FMT requires donor bacteria to engraft in the patient's gut, the forces governing engraftment in humans are unknown. Here we use an ongoing clinical experiment, the treatment of recurrent Clostridium diffic...
Article
Full-text available
Oral squamous cell carcinomas are a major cause of morbidity and mortality, and tobacco usage, alcohol consumption, and poor oral hygiene are established risk factors. To date, no large-scale case-control studies have considered the effects of these risk factors on the composition of the oral microbiome, nor microbial community associations with or...
Article
Full-text available
Background Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes. Methods We performed metagenomic sequencing of monthly stool samples from 20 IBD patients and...
Article
Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2′,2′-difluorodeoxycytidine) into its inactive form, 2′,2′-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bac...
Article
Our 2014 study published in Cell Host & Microbe, "The Treatment-Naive Microbiome in New-Onset Crohn's Disease,'' was designed to improve our understanding of the microbiome's role in Crohn's disease by studying a unique, well-suited cohort and sample set. This commentary provides a hindsight perspective of this original study as well as future outl...
Article
Full-text available
Objective Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case–control analysis of the gut microbiota, the host ge...
Article
Background: The microbiota in the lumen of patients with Crohn's disease (CD) is characterized by reduced diversity, particularly Firmicutes and Bacteroidetes. It is unknown whether the introduction of the intestinal microbiota from healthy individuals could correct this dysbiosis and reverse mucosal inflammation. We investigated the response to f...
Article
Full-text available
Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals. However, mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of m...
Article
Full-text available
Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial ab...
Article
Full-text available
Public transit systems are ideal for studying the urban microbiome and interindividual community transfer. In this study, we used 16S amplicon and shotgun metagenomic sequencing to profile microbial communities on multiple transit surfaces across train lines and stations in the Boston metropolitan transit system. The greatest determinant of microbi...
Article
Full-text available
Background & Aims Microbial dysbiosis and aberrant host–microbe interactions in the gut are believed to contribute to the development and progression of Crohn’s disease (CD). Microbiome studies in CD typically have focused on microbiota in feces or superficial mucosal layers of the colon because accessing DNA from deeper layers of the bowel is chal...
Article
Full-text available
“Normal” for the gut microbiota For the benefit of future clinical studies, it is critical to establish what constitutes a “normal” gut microbiome, if it exists at all. Through fecal samples and questionnaires, Falony et al. and Zhernakova et al. targeted general populations in Belgium and the Netherlands, respectively. Gut microbiota composition c...
Article
Full-text available
BackgroundA gluten-free diet (GFD) is the most commonly adopted special diet worldwide. It is an effective treatment for coeliac disease and is also often followed by individuals to alleviate gastrointestinal complaints. It is known there is an important link between diet and the gut microbiome, but it is largely unknown how a switch to a GFD affec...
Article
According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common...
Article
Full-text available
Background Obesity and type 2 diabetes (T2D) are linked both with host genetics and with environmental factors, including dysbioses of the gut microbiota. However, it is unclear whether these microbial changes precede disease onset. Twin cohorts present a unique genetically-controlled opportunity to study the relationships between lifestyle factors...
Article
Full-text available
Background and aims: There is an unexplained association between ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) with the intestinal microbiota implicated as an important factor. The study aim was to compare the structure of the intestinal microbiota of patients with UC with and without PSC. Methods: UC patients with PSC (PSC-UC...
Article
Full-text available
Background: The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding ef...
Article
Analyses of metagenomic datasets that are sequenced to a depth of billions or trillions of bases can uncover hundreds of microbial genomes, but naive assembly of these data is computationally intensive, requiring hundreds of gigabytes to terabytes of RAM. We present latent strain analysis (LSA), a scalable, de novo pre-assembly method that separate...
Article
Full-text available
Rationale: Evidence suggests the gut microbiome is involved in the development of cardiovascular disease (CVD), with the host-microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for CVD from large-scale studies in humans. In particular, the...
Article
An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short...
Article
Full-text available
Significance Recent surveys of the microbial communities living on and in the human body—the human microbiome—have revealed strong variation in community membership between individuals. Some of this variation is stable over time, leading to speculation that individuals might possess unique microbial “fingerprints” that distinguish them from the pop...
Article
Full-text available
Pouchitis is common after ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC). Similarly to inflammatory bowel disease (IBD), both host genetics and the microbiota are implicated in its pathogenesis. We use the IPAA model of IBD to associate mucosal host gene expression with mucosal microbiomes and clinical outcomes. We analyze...
Article
The gut microbiome is widely studied by fecal sampling, but the extent to which stool reflects the commensal composition at intestinal sites is poorly understood. We investigated this relationship in rhesus macaques by 16S sequencing feces and paired lumenal and mucosal samples from ten sites distal to the jejunum. Stool composition correlated high...
Article
Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial ab...
Article
Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals. However, mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of m...
Article
Full-text available
This report details the outcome of the 1st Skin Microbiota Workshop, Boulder, CO, held on October 15th-16th 2012. The workshop was arranged to bring Department of Defense personnel together with experts in microbial ecology, human skin physiology and anatomy, and computational techniques for interrogating the microbiome to define research frontiers...
Article
Full-text available
Human genetics and host-associated microbial communities have been associated independently with a wide range of chronic diseases. One of the strongest associations in each case is inflammatory bowel disease (IBD), but disease risk cannot be explained fully by either factor individually. Recent findings point to interactions between host genetics a...
Article
The human microbiome has become a recognized factor in promoting and maintaining health. We outline opportunities in interdisciplinary research, analytical rigor, standardization, and policy development for this relatively new and rapidly developing field. Advances in these aspects of the research community may in turn advance our understanding of...
Conference Paper
Full-text available
Background / Purpose: Type 1 diabetes (T1D) results from autoimmune-mediated destruction of pancreatic islet beta cells; however, the factors that contribute to T1D progression are poorly understood. We assessed the dynamics of the human gut microbiome through infancy and its relation to T1D status. Infants at risk for T1D were tracked by monthly...
Article
Full-text available
Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, pa...
Article
Full-text available
Significance Recent years have seen incredible growth in both the scale and specificity of projects analyzing the microbial organisms living in and on the human body (the human microbiome). Such studies typically require subjects to report to clinics for sample collection, a complicated practice that is impractical for large studies. To address the...
Article
Full-text available
Although the composition of the human microbiome is now well-studied, the microbiota’s >8 million genes and their regulation remain largely uncharacterized. This knowledge gap is in part because of the difficulty of acquiring large numbers of samples amenable to functional studies of the microbiota. We conducted what is, to our knowledge, one of th...
Article
Full-text available
Background: Recurrent Clostridium difficile infection (CDI) with poor response to standard antimicrobial therapy is a growing medical concern. We aimed to investigate the outcomes of fecal microbiota transplant (FMT) for relapsing CDI using a frozen suspension from unrelated donors, comparing colonoscopic and nasogastric tube (NGT) administration....
Article
Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal loc...
Article
Few concepts in recent years have garnered more disease research attention than that of the intestinal (i.e., “gut”) microbiome. This emerging interest has included investigations of the microbiome's role in the pathogenesis of a variety of autoimmune disorders including type 1 diabetes (T1D). Indeed, a growing number of recent studies of patients...
Article
Studies of the roles of microbial communities in the development of inflammatory bowel diseases (IBD) have reached an important milestone. A decade of genome-wide association studies and other genetic analyses have linked IBD with loci that implicate an aberrant immune response to the intestinal microbiota. More recently, profiling studies of the i...
Article
Full-text available
Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive m...
Article
Full-text available
Microbial genome sequencing is one of the longest-standing areas of biological database development, but high-throughput, low-cost technologies have increased its throughput to an unprecedented number of new genomes per year. Several thousand microbial genomes are now available, necessitating new approaches to organizing information on gene functio...
Article
Full-text available
Glycoside hydrolases (GHs), the enzymes that breakdown complex carbohydrates, are a highly diversified class of key enzymes associated with the gut microbiota and its metabolic functions. To learn more about the diversity of GHs and their potential role in a variety of gut microbiomes, we used a combination of 16S, metagenomic and targeted amplicon...

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