scispace - formally typeset
Search or ask a question
Author

Gregory Humphrey

Other affiliations: University of Colorado Boulder
Bio: Gregory Humphrey is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Microbiome & Medicine. The author has an hindex of 16, co-authored 33 publications receiving 2717 citations. Previous affiliations of Gregory Humphrey include University of Colorado Boulder.
Topics: Microbiome, Medicine, Biology, Metabolome, Gut flora

Papers
More filters
Journal ArticleDOI
01 Nov 2017-Nature
TL;DR: A meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project is presented, creating both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity.
Abstract: Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity.

1,676 citations

Journal ArticleDOI
16 Apr 2013-eLife
TL;DR: Dog ownership significantly increased the shared skin microbiota in cohabiting adults, and dog-owning adults shared more ‘skin’ microbiota with their own dogs than with other dogs, suggesting that direct and frequent contact with the authors' cohabitants may significantly shape the composition of their microbial communities.
Abstract: The human body is home to many different microorganisms, with a range of bacteria, fungi and archaea living on the skin, in the intestine and at various other sites in the body. While many of these microorganisms are beneficial to their human hosts, we know very little about most of them. Early research focused primarily on comparing the microorganisms found in healthy individuals with those found in individuals suffering from a particular illness. More recently researchers have become interested in more general issues, such as understanding how these collections of microorganisms, which are also known as the human microbiota or the human microbiome, become established, and exploring the causes of similarities and differences between the microbiota of individuals. We now know that the communities of microorganisms found in the intestines of genetically related people tend to be more similar than those of people who are not related. Moreover, the communities of microorganisms found in the intestines of non-related adults living in the same household are more similar than those of unrelated adults living in different households. We also know that the range of microorganisms found in the intestine changes dramatically between birth and the age of 3 years. However, these studies have focused on the intestine, and little is known about the effect of relatedness, cohabitation and age on the microbiota at other body sites. Song et al. compared the microorganisms found on the skin, on the tongue and in the intestines of 159 people—and 36 dogs—in 60 families. They found that co-habitation resulted in the communities of microorganisms being more similar to each other, with those on the skin being the most similar. This was true for all comparisons, including human pairs, dog pairs and human–dog pairs. This suggests that humans probably acquire many of the microorganisms on their skin through direct contact with their surroundings, and that humans tend to share more microbes with individuals, including their pets, with which they are in frequent contact. Song et al. also discovered that, unlike what happens in the intestine, the microbial communities on the skin and tongue of infants and children were relatively similar to those of adults. Overall, these findings suggest that the communities of microorganisms found in the intestine changes with age in a way that differs significantly from those found on the skin and tongue.

842 citations

Journal ArticleDOI
15 Oct 2013-eLife
TL;DR: It is shown that postmortem microbial community changes are dramatic, measurable, and repeatable in a mouse model system, allowing PMI to be estimated within approximately 3 days over 48 days, and suggested that microbial community data can be developed into a forensic tool for estimating PMI.
Abstract: Our bodies—especially our skin, our saliva, the lining of our mouth and our gastrointestinal tract—are home to a diverse collection of bacteria and other microorganisms called the microbiome. While the roles played by many of these microorganisms have yet to be identified, it is known that they contribute to the health and wellbeing of their host by metabolizing indigestible compounds, producing essential vitamins, and preventing the growth of harmful bacteria. They are important for nutrient and carbon cycling in the environment. The advent of advanced sequencing techniques has made it feasible to study the composition of this microbial community, and to monitor how it changes over time or how it responds to events such as antibiotic treatment. Sequencing studies have been used to highlight the significant differences between microbial communities found in different parts of the body, and to follow the evolution of the gut microbiome from birth. Most of these studies have focused on live animals, so little is known about what happens to the microbiome after its host dies. In particular, it is not known if the changes that occur after death are similar for all individuals. Moreover, the decomposing animal supplies nutrients and carbon to the surrounding ecosystem, but its influence on the microbial community of its immediate environment is not well understood. Now Metcalf et al. have used high-throughput sequencing to study the bacteria and other microorganisms (such as nematodes and fungi) in dead and decomposing mice, and also in the soil beneath them, over the course of 48 days. The changes were significant and also consistent across the corpses, with the microbial communities in the corpses influencing those in the soil, and vice versa. Metcalf et al. also showed that these measurements could be used to estimate the postmortem interval (the time since death) to within approximately 3 days, which suggests that the work could have applications in forensic science.

273 citations

Journal ArticleDOI
TL;DR: The findings indicate that mammalian gut microbiome plasticity in response to dietary shifts over both the lifespan of an individual host and the evolutionary history of a given host species is constrained by host physiological evolution, and the gut microbiome cannot be considered separately from host physiology when describing host nutritional strategies and the emergence of host dietary niches.
Abstract: Over the past decade several studies have reported that the gut microbiomes of mammals with similar dietary niches exhibit similar compositional and functional traits. However, these studies rely heavily on samples from captive individuals and often confound host phylogeny, gut morphology, and diet. To more explicitly test the influence of host dietary niche on the mammalian gut microbiome we use 16S rRNA gene amplicon sequencing and shotgun metagenomics to compare the gut microbiota of 18 species of wild non-human primates classified as either folivores or closely related non-folivores, evenly distributed throughout the primate order and representing a range of gut morphological specializations. While folivory results in some convergent microbial traits, collectively we show that the influence of host phylogeny on both gut microbial composition and function is much stronger than that of host dietary niche. This pattern does not result from differences in host geographic location or actual dietary intake at the time of sampling, but instead appears to result from differences in host physiology. These findings indicate that mammalian gut microbiome plasticity in response to dietary shifts over both the lifespan of an individual host and the evolutionary history of a given host species is constrained by host physiological evolution. Therefore, the gut microbiome cannot be considered separately from host physiology when describing host nutritional strategies and the emergence of host dietary niches.

210 citations

Journal ArticleDOI
07 Jan 2020-Mbio
TL;DR: Assessment of gut microbiomes from ∼900 vertebrate species, including 315 mammals and 491 birds, concludes that host-gut microbiome phylosymbiosis depends on factors convergently absent in birds and bats, potentially associated with physiological adaptations to flight.
Abstract: Diet and host phylogeny drive the taxonomic and functional contents of the gut microbiome in mammals, yet it is unknown whether these patterns hold across all vertebrate lineages. Here, we assessed gut microbiomes from ∼900 vertebrate species, including 315 mammals and 491 birds, assessing contributions of diet, phylogeny, and physiology to structuring gut microbiomes. In most nonflying mammals, strong correlations exist between microbial community similarity, host diet, and host phylogenetic distance up to the host order level. In birds, by contrast, gut microbiomes are only very weakly correlated to diet or host phylogeny. Furthermore, while most microbes resident in mammalian guts are present in only a restricted taxonomic range of hosts, most microbes recovered from birds show little evidence of host specificity. Notably, among the mammals, bats host especially bird-like gut microbiomes, with little evidence for correlation to host diet or phylogeny. This suggests that host-gut microbiome phylosymbiosis depends on factors convergently absent in birds and bats, potentially associated with physiological adaptations to flight. Our findings expose major variations in the behavior of these important symbioses in endothermic vertebrates and may signal fundamental evolutionary shifts in the cost/benefit framework of the gut microbiome.IMPORTANCE In this comprehensive survey of microbiomes of >900 species, including 315 mammals and 491 birds, we find a striking convergence of the microbiomes of birds and animals that fly. In nonflying mammals, diet and short-term evolutionary relatedness drive the microbiome, and many microbial species are specific to a particular kind of mammal, but flying mammals and birds break this pattern with many microbes shared across different species, with little correlation either with diet or with relatedness of the hosts. This finding suggests that adaptation to flight breaks long-held relationships between hosts and their microbes.

176 citations


Cited by
More filters
01 Jun 2012
TL;DR: SPAdes as mentioned in this paper is a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler and on popular assemblers Velvet and SoapDeNovo (for multicell data).
Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

10,124 citations

Journal ArticleDOI
TL;DR: In this article, a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation is described and validated, which addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities.
Abstract: This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

3,060 citations

Journal ArticleDOI
TL;DR: The results illustrate the importance of parameter tuning for optimizing classifier performance, and the recommendations regarding parameter choices for these classifiers under a range of standard operating conditions are made.
Abstract: Taxonomic classification of marker-gene sequences is an important step in microbiome analysis. We present q2-feature-classifier ( https://github.com/qiime2/q2-feature-classifier ), a QIIME 2 plugin containing several novel machine-learning and alignment-based methods for taxonomy classification. We evaluated and optimized several commonly used classification methods implemented in QIIME 1 (RDP, BLAST, UCLUST, and SortMeRNA) and several new methods implemented in QIIME 2 (a scikit-learn naive Bayes machine-learning classifier, and alignment-based taxonomy consensus methods based on VSEARCH, and BLAST+) for classification of bacterial 16S rRNA and fungal ITS marker-gene amplicon sequence data. The naive-Bayes, BLAST+-based, and VSEARCH-based classifiers implemented in QIIME 2 meet or exceed the species-level accuracy of other commonly used methods designed for classification of marker gene sequences that were evaluated in this work. These evaluations, based on 19 mock communities and error-free sequence simulations, including classification of simulated “novel” marker-gene sequences, are available in our extensible benchmarking framework, tax-credit ( https://github.com/caporaso-lab/tax-credit-data ). Our results illustrate the importance of parameter tuning for optimizing classifier performance, and we make recommendations regarding parameter choices for these classifiers under a range of standard operating conditions. q2-feature-classifier and tax-credit are both free, open-source, BSD-licensed packages available on GitHub.

2,475 citations

Journal ArticleDOI
05 Jan 2018-Science
TL;DR: The results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients and could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti–PD-L1 therapy.
Abstract: Anti–PD-1–based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition of the patients’ microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16 S ribosomal RNA gene sequencing, metagenomic shotgun sequencing, and quantitative polymerase chain reaction for selected bacteria. A significant association was observed between commensal microbial composition and clinical response. Bacterial species more abundant in responders included Bifidobacterium longum , Collinsella aerofaciens , and Enterococcus faecium. Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti–PD-L1 therapy. Our results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients.

1,820 citations

Journal ArticleDOI
TL;DR: Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
Abstract: The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

1,775 citations