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George Weinstock

George Weinstock
Jackson Laboratory for Genomic Medicine, Farmington, CT, USA · Microbial Genomics

Ph.D. 1977 MIT

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876
Publications
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158,660
Citations

Publications

Publications (876)
Article
Full-text available
There is a current need for enhancing our insight in the effects of antimicrobial treatment on the composition of human microbiota. Also, the spontaneous restoration of the microbiota after antimicrobial treatment requires better understanding. This is best addressed in well-defined animal models. We here present a model in which immune-competent o...
Article
Atopic dermatitis (AD) is one of the most common diseases in pediatric patients, with over 12.5% of US children diagnosed with the condition.¹ Previous studies have shown that the impaired skin barrier caused by AD leads to the development of other atopic conditions later in life.² The rate of AD among black children in Africa is similar to reporte...
Article
Background: Full-fixed appliance orthodontic treatment (commonly called braces) increases plaque accumulation and the risk of gingivitis and periodontitis. However, little consensus exists on changes to subgingival microbiota and specific periodontopathogens during treatment with braces. Prior studies have been hampered by selection biases due to...
Article
Full-text available
Substance use disorders (SUDs) remain a significant public health challenge, affecting tens of millions of individuals worldwide each year. Often comorbid with other psychiatric disorders, SUD can be poly-drug and involve several different substances including cocaine, opiates, nicotine, and alcohol. SUD has a strong genetic component. Much of SUD...
Article
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The gut microbiome plays a significant role in health and disease, and there is mounting evidence indicating that the microbial composition is regulated in part by host genetics. Heritability estimates for microbial abundance in mice and humans range from (0.05–0.45), indicating that 5–45% of inter-individual variation can be explained by genetics....
Article
The molecular circadian clock and symbiotic host-microbe relationships both evolved as mechanisms that enhance metabolic responses to environmental challenges. The gut microbiome benefits the host by breaking down diet-derived nutrients indigestible by the host and generating microbiota-derived metabolites that support host metabolism. Similarly, c...
Article
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Although the taxonomic composition of the human microbiome varies tremendously across individuals, its gene composition or functional capacity is highly conserved — implying an ecological property known as functional redundancy. Such functional redundancy has been hypothesized to underlie the stability and resilience of the human microbiome, but th...
Article
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Background: Gut microbial diversity and composition play important roles in health. This cross-sectional study was designed to test the hypothesis that hospitalized children who may be relatively immunocompromised (IC), defined as those with cancer, sickle cell disease (SCD), transplantation, or receiving immunosuppressive therapy) would have decre...
Article
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The biological basis of exercise behavior is increasingly relevant for maintaining healthy lifestyles. Various quantitative genetic studies and selection experiments have conclusively demonstrated substantial heritability for exercise behavior in both humans and laboratory rodents. In the "High Runner" selection experiment, 4 replicate lines of Mus...
Article
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Sputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNA-seq) of sputum samples can be challenging to interpret due to the complex and heterogeneous mixtures of human cells and exogenous (microbial) material. In this study, we develop a pipeline that integrates dimensionality reducti...
Article
Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22 producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically, we addressed the hypothesis th...
Article
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The human microbiome plays a critically important role in health and disease, but current understanding of the mechanisms underlying the interactions between the varying microbiome and the different host environments is lacking. Having access to a database of fully sequenced bacterial genomes provides invaluable insights into microbial functions, b...
Preprint
Although the taxonomic composition of the human microbiome varies tremendously across individuals, its gene composition or functional capacity is highly conserved ¹⁻⁵ ---implying an ecological property known as functional redundancy . Such functional redundancy is thought to underlie the stability and resilience of the human microbiome 6,7 , but it...
Article
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Host genetic diversity provides a variable selection environment and physiological context for microbiota and their interaction with host physiology. Using a highly diverse mouse population, Bubier et al. identified that Odoribacter abundance influences sleep archi-tecture in a manner... The microbiome influences health and disease through complex...
Article
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Regressing an outcome or dependent variable onto a set of input or independent variables allows the analyst to measure associations between the two so that changes in the outcome can be described by and predicted by changes in the inputs. While there are many ways of doing this in classical statistics, where the dependent variable has certain prope...
Preprint
Whole genome bacterial sequences are required to better understand microbial functions, niches-pecific bacterial metabolism, and disease states. Although genomic sequences are available for many of the human-associated bacteria from commonly tested body habitats (e.g. stool), as few as 13% of bacterial-derived reads from other sites such as the ski...
Article
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The airway microbiome has an important role in asthma pathophysiology. However, little is known on the relationships between the airway microbiome of asthmatic children, loss of asthma control, and severe exacerbations. Here we report that the microbiota’s dynamic patterns and compositions are related to asthma exacerbations. We collected nasal blo...
Article
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There is limited understanding of how walnut consumption inhibits the development of colorectal cancer(CRC). A possible mechanism may involve alterations to the gut microbiota. In this study, the effects of walnut on gut microbiota was tested in a mouse tumor bioassay using the colonotropic carcinogen, azoxymethane (AOM) added to the Total Western...
Article
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Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesions in the colon that can be detected by high-definition chromoendoscopy with contrast dye spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this s...
Article
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The 16S rRNA gene has been a mainstay of sequence-based bacterial analysis for decades. However, high-throughput sequencing of the full gene has only recently become a realistic prospect. Here, we use in silico and sequence-based experiments to critically re-evaluate the potential of the 16S gene to provide taxonomic resolution at species and strai...
Preprint
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Motivation Mobile genetic elements (MGEs) are genetic material that can transfer between bacterial cells and move to new locations within a single bacterial genome. These elements range from several hundred to tens of thousands of bases, and are often bordered by repeat regions, which makes resolving these elements difficult with short-read sequenc...
Preprint
Full-text available
Sputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNAseq) can be used on sputum, but it can be challenging to interpret because sputum contains a complex and heterogeneous mixture of human cells and exogenous (microbial) material. In this study, we developed a methodology that int...
Article
Full-text available
Motivation: Metagenomics is the study of genetic materials directly sampled from natural habitats. It has the potential to reveal previously hidden diversity of microscopic life largely due to the existence of highly parallel and low-cost next-generation sequencing technology. Conventional approaches align metagenomic reads onto known reference ge...
Conference Paper
Purpose: Oropharyngeal cancer (OPC) incidence continues to increase dramatically in the US. Accumulating evidence suggests that oral microbiota (communities of microorganisms that reside in the oral cavity) may influence cancer treatment-related toxicities. We sought to examine the composition and diversity of oral microbiota in OPC patients prior...
Conference Paper
Purpose: Oropharyngeal cancer (OPC) incidence continues to increase dramatically in the US. Accumulating evidence suggests that oral microbiota (communities of microorganisms that reside in the oral cavity) may influence cancer treatment-related toxicities. We sought to examine the composition and diversity of oral microbiota in OPC patients prior...
Preprint
Full-text available
Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion in the colon that can be detected by high-definition chromoendoscopy with contrast dye-spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this st...
Article
Full-text available
Precision health relies on the ability to assess disease risk at an individual level, detect early preclinical conditions and initiate preventive strategies. Recent technological advances in omics and wearable monitoring enable deep molecular and physiological profiling and may provide important tools for precision health. We explored the ability o...
Article
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Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and pe...
Article
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The NIH Human Microbiome Project (HMP) has been carried out over ten years and two phases to provide resources, methods, and discoveries that link interactions between humans and their microbiomes to health-related outcomes. The recently completed second phase, the Integrative Human Microbiome Project, comprised studies of dynamic changes in the mi...
Article
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Background Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the respo...
Article
Full-text available
Importance: In animal models, the early life gut microbiome influences later neurodevelopment. Corresponding data in human populations are lacking. Objective: To study associations between the gut microbiome in infants and development at preschool age measured by the Ages and Stages Questionnaire, third edition (ASQ-3). Design, setting, and par...
Preprint
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The geographic and phylogenetic scale of ecologically relevant microbial diversity is still poorly understood. Using a model mutualism, fungus-growing ants and their defensive bacterial associate Pseudonocardia , we analyzed genetic diversity and biosynthetic potential in 46 strains isolated from ant colonies in a 20km transect near Barro Colorado...
Article
Iron deficiency and iron deficiency anemia are highly prevalent in low-income countries, especially among young children. Hepcidin is the major regulator of systemic iron homeostasis. It controls dietary iron absorption, dictates whether absorbed iron is made available in circulation for erythropoiesis and other iron-demanding processes, and predic...
Article
Despite some notable progress in data sharing policies and practices, restrictions are still often placed on the open and unconditional use of various genomic data after they have received official approval for release to the public domain or to public databases. These restrictions, which often conflict with the terms and conditions of the funding...
Article
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Background The intestinal microbiome modulates local and systemic immune responses and may impact clinical outcomes. However, there are few studies in pediatric patients. We conducted a cross-sectional study of fecal microbiomes in hospitalized children on a single inpatient unit at Children’s Hospital at Montefiore, Bronx, New York in 2016–2017 to...
Article
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In the version of this article published, in the Online Methods eight citations to supplementary material refer to the wrong supplementary items. See the correction notice for full details.
Article
Objectives: To determine the association between diet during pregnancy and infancy, including breastfeeding vs formula feeding, solid food introduction, and the infant intestinal microbiome. Study design: Infants participating in the Vitamin D Antenatal Asthma Reduction Trial were included in this study (n = 323). Maternal and infant diets were...
Article
p>Mounting evidence suggests that a prominent T cell response in the colorectal cancer (CRC) tumor microenvironment is a valuable prognostic indicator, independent of stage at diagnosis. However, the strength and quality of host immune responses are highly variable across patients, and the factors that influence this variability are not well unders...
Preprint
Full-text available
The role of the microbiome in health and disease involves complex networks of host genetics, genomics, microbes and environment. Identifying the mechanisms of these interactions has remained challenging. Systems genetics in the laboratory mouse enables data-driven discovery of network components and mechanisms of host-microbial interactions underly...
Article
Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroida...
Article
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Objective: In humans, the ontogeny of obesity throughout the life course and the genetics underlying it has been historically difficult to study. We compared, in a non-human primate model, the lifelong growth trajectories of obese and non-obese adults, to assess the heritability of and map potential genomic regions implicated in growth and obesity...
Article
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In the version of this Perspective originally published, the first and last name of co-author Manimozhiyan Arumugam were switched. This has now been corrected in all versions of the Perspective.
Article
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Volume 61, no. 10, e00816-17, 2017, https://doi.org/10.1128/AAC.00816-17. Page 11: The following sentence should be added to the second paragraph of Acknowledgments. “This work was supported in part by a UTHealth Presidential Collaborative Award to C.A.A.” Copyright
Article
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In the version of this article initially published, the following acknowledgment was omitted: A.L. was supported by the Russian Science Foundation (grant number 14-50-00069). The error has been corrected in the HTML and PDF versions of the article. © 2018 Nature America, Inc., part of Springer Nature. All rights reserved.
Article
The lung microbiota has received less attention compared to other body sites, in part because its study carries special technological difficulties related to obtaining reliable samples as compared to other body niches. The limited number of studies on the sputum microbiota on TB patients and controls available so far have reported inconsistent, and...
Article
Advances in omics technologies now allow an unprecedented level of phenotyping for human diseases, including obesity, in which individual responses to excess weight are heterogeneous and unpredictable. To aid the development of better understanding of these phenotypes, we performed a controlled longitudinal weight perturbation study combining multi...
Article
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Population stratification is a useful approach for a better understanding of complex biological problems in human health and wellbeing. The proposal that such stratification applies to the human gut microbiome, in the form of distinct community composition types termed enterotypes, has been met with both excitement and controversy. In view of accum...
Article
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There is growing concern that interventions that alter microbial ecology can adversely affect health. We characterised the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal carriage and the bacterial component of the nasopharyngeal microbiome during infancy. Newborns were recruited into three groups as follows: Group1...
Article
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Vervet monkeys are among the most widely distributed nonhuman primates, show considerable phenotypic diversity, and have long been an important biomedical model for a variety of human diseases and in vaccine research. Using whole-genome sequencing data from 163 vervets sampled from across Africa and the Caribbean, we find high diversity within and...
Article
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By analyzing multitissue gene expression and genome-wide genetic variation data in samples from a vervet monkey pedigree, we generated a transcriptome resource and produced the first catalog of expression quantitative trait loci (eQTLs) in a nonhuman primate model. This catalog contains more genome-wide significant eQTLs per sample than comparable...