scholarly journals Gut Microbiome Toxicity: Connecting the Environment and Gut Microbiome-Associated Diseases

Toxics ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 19 ◽  
Author(s):  
Pengcheng Tu ◽  
Liang Chi ◽  
Wanda Bodnar ◽  
Zhenfa Zhang ◽  
Bei Gao ◽  
...  
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Human Disease ◽  
Disease Risk ◽  
Environmental Chemicals ◽  
Toxic Effects ◽  
Toxicity Evaluation ◽  
Human Gut ◽  
Associated Diseases ◽  
Environmental Agents

The human gut microbiome can be easily disturbed upon exposure to a range of toxic environmental agents. Environmentally induced perturbation in the gut microbiome is strongly associated with human disease risk. Functional gut microbiome alterations that may adversely influence human health is an increasingly appreciated mechanism by which environmental chemicals exert their toxic effects. In this review, we define the functional damage driven by environmental exposure in the gut microbiome as gut microbiome toxicity. The establishment of gut microbiome toxicity links the toxic effects of various environmental agents and microbiota-associated diseases, calling for more comprehensive toxicity evaluation with extended consideration of gut microbiome toxicity.

scholarly journals Stable Engraftment of a Human Gut Bacterial Microbiome in Double Humanized BLT-mice

2019 ◽  
Author(s):  
Lance Daharsh ◽  
Amanda E. Ramer-Tait ◽  
Qingsheng Li
Keyword(s):  
Immune System ◽  
Gut Microbiome ◽  
Human Disease ◽  
Humanized Mice ◽  
Rrna Gene ◽  
Human Immune System ◽  
Human Gut ◽  
Healthy Human ◽  
Human Immune

AbstractBackgroundHumanized mice featuring a functional human immune system are an important pre-clinical model for examining immune responses to human-specific pathogens. This model has been widely utilized to study human diseases that are otherwise impossible or difficult to investigate in humans or with other animal models. However, one limitation of using humanized mice is their native murine gut microbiome, which significantly differs from the one found in humans. These differences may be even greater for mice housed and bred in specific pathogen free conditions. Given the importance of the gut microbiome to human health and disease, these differences may profoundly impact the ability to translate the results from humanized mice studies to human disease. Further, there is a critical need for improved pre-clinical models to study the complex in vivo relationships of the gut microbiome, immune system, and human disease. We therefore created double humanized mice with both a functional human immune system and stable human-like gut microbiome.ResultsSurgery was performed on NOD.Cg-PrkdcscidII2rgtm1Wjl/SzJ (NSG) mice to create bone-marrow, liver, thymus (BLT) humanized mice. After immune reconstitution, mice were treated with broad spectrum antibiotics to deplete murine gut bacteria and then transplanted with fecal material from healthy human donors. Characterization of 173 fecal samples obtained from 45 humanized mice revealed that double humanized mice had unique 16S rRNA gene profiles consistent with those of the individual human donor samples. Importantly, transplanted human-like gut microbiomes were stable in mice for the duration of the study, up to 14.5 weeks post-transplant. Microbiomes of double humanized mice also harbored predicted functional capacities that more closely resembled those of the human donors compared to humanized mice.ConclusionsHere, we describe successful engraftment of a stable human microbiome in BLT humanized mice to further improve this preclinical humanized mouse model. These double humanized mice represent a unique and tractable new model to study the complex relationships between the human gut microbiome, human immune system, and human disease in vivo.

scholarly journals Polyphenol utilization proteins in human gut microbiome

2021 ◽  
Author(s):  
Bo Zheng ◽  
Yinchao He ◽  
Pengxiang Zhang ◽  
Yi-Xin Huo ◽  
Yanbin Yin
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Sequence Similarity ◽  
Gene Clusters ◽  
Metagenomic Data ◽  
Human Populations ◽  
Human Gut ◽  
Systematic Classification ◽  
Dietary Polyphenols ◽  
Human Gut Microbiome

Dietary polyphenols can significantly benefit human health, but their bioavailability is metabolically controlled by human gut microbiota. To facilitate the study of polyphenol metabolism for human gut health, we have manually curated experimentally characterized polyphenol utilization proteins (PUPs) from published literature. This resulted in 60 experimentally characterized PUPs (named seeds) with various metadata, such as species and substrate. Further database search found 107,851 homologs of the seeds from UniProt and UHGP (Unified Human Gastrointestinal Protein) databases. All PUP seeds and homologs were classified into protein classes, families and subfamilies based on Enzyme Commission (EC) numbers, Pfam (protein family) domains and sequence similarity networks. By locating PUP homologs in the genomes of UHGP, we have identified 1,074 physically linked PUP gene clusters (PGCs), which are potentially involved in polyphenol metabolism in the human gut. The gut microbiome of Africans was consistently ranked the top in terms of the abundance and prevalence of PUP homologs and PGCs among all geographical continents. This reflects the fact that dietary polyphenols are more commonly consumed by African population than other populations such as Europeans and North Americans. A case study of the Hadza hunter-gatherer microbiome verified the feasibility of using dbPUP to profile metagenomic data for biologically meaningful discovery, suggesting an association between diet and PUP abundance. A Pfam domain enrichment analysis of PGCs identified a number of putatively novel PUP families. Lastly, a user-friendly web interface ( https://bcb.unl.edu/dbpup/ ) provides all the data online to facilitate the research of polyphenol metabolism for improved human health. Importance Long-term consumption of polyphenol-rich foods have been shown to lower the risk of various human diseases such as cardiovascular diseases, cancers, and metabolic diseases. Raw polyphenols are often enzymatically processed by gut microbiome, which encode various polyphenol utilization proteins (PUPs) to produce metabolites with much higher bioaccessibility to gastrointestinal cells. This study delivered dbPUP as an online database for experimentally characterized PUPs and their homologs in human gut microbiome. This work also performed a systematic classification of PUPs into enzyme classes, families, and subfamilies. The signature Pfam domains were identified for PUP families, enabling conserved domain-based PUP annotation. This standardized sequence similarity-based PUP classification system offered a guideline for the future inclusion of new experimentally characterized PUPs and the creation of new PUP families. An in-depth data analysis was further conducted on PUP homologs and physically linked PUP gene clusters (PGCs) in gut microbiomes of different human populations.

scholarly journals Metaproteomics as a tool for studying the protein landscape of human-gut bacterial species

2021 ◽  
Author(s):  
Moses Stamboulian ◽  
Jamie Canderan ◽  
Yuzhen Ye
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
De Novo ◽  
Bacterial Species ◽  
Individual Species ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Microbial Species ◽  
Microbial Organisms

AbstractHost-microbiome interactions and the microbial community have broad impact in human health and diseases. Most microbiome based studies are performed at the genome level based on next-generation sequencing techniques, but metaproteomics is emerging as a powerful technique to study microbiome functional activity by characterizing the complex and dynamic composition of microbial proteins. We conducted a large-scale survey of human gut microbiome metaproteomic data to identify generalist species that are ubiquitously expressed across all samples and specialists that are highly expressed in a small subset of samples associated with a certain phenotype. We were able to utilize the metaproteomic mass spectrometry data to reveal the protein landscapes of these species, which enables the characterization of the expression levels of proteins of different functions and underlying regulatory mechanisms, such as operons. Finally, we were able to recover a large number of open reading frames (ORFs) with spectral support, which were missed by de novo protein-coding gene predictors. We showed that a majority of the rescued ORFs overlapped with de novo predicted proteincoding genes, but on opposite strands or on different frames. Together, these demonstrate applications of metaproteomics for the characterization of important gut bacterial species. Results are available for public access at https://omics.informatics.indiana.edu/GutBac.Author summaryMany reference genomes for studying human gut microbiome are available, but knowledge about how microbial organisms work is limited. Identification of proteins at individual species or community level provides direct insight into the functionality of microbial organisms. By analyzing more than a thousand metaproteomics datasets, we examined protein landscapes of more than two thousands of microbial species that may be important to human health and diseases. This work demonstrated new applications of metaproteomic datasets for studying individual genomes. We made the analysis results available through the GutBac website, which we believe will become a resource for studying microbial species important for human health and diseases.

scholarly journals Interplay between the human gut microbiome and host metabolism

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Alessia Visconti ◽  
Caroline I. Le Roy ◽  
Fabio Rosa ◽  
Niccolò Rossi ◽  
Tiphaine C. Martin ◽  
...  
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Blood Metabolites ◽  
Sequencing Data ◽  
Human Gut ◽  
Metabolic Potential ◽  
Microbial Ecosystem ◽  
Microbial Metabolic Potential ◽  
Host Metabolism

Abstract The human gut is inhabited by a complex and metabolically active microbial ecosystem. While many studies focused on the effect of individual microbial taxa on human health, their overall metabolic potential has been under-explored. Using whole-metagenome shotgun sequencing data in 1,004 twins, we first observed that unrelated subjects share, on average, almost double the number of metabolic pathways (82%) than species (43%). Then, using 673 blood and 713 faecal metabolites, we found metabolic pathways to be associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species showed less than 3,000 associations. Finally, we estimated that the microbiome was involved in a dialogue between 71% of faecal, and 15% of blood, metabolites. This study underlines the importance of studying the microbial metabolic potential rather than focusing purely on taxonomy to find therapeutic and diagnostic targets, and provides a unique resource describing the interplay between the microbiome and the systemic and faecal metabolic environments.

scholarly journals Mapping the microbial interactome: Statistical and experimental approaches for microbiome network inference

2019 ◽  
Vol 244 (6) ◽  
pp. 445-458 ◽  
Author(s):  
Anders B Dohlman ◽  
Xiling Shen
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Network Inference ◽  
Therapeutic Strategies ◽  
Microbial Interactions ◽  
Interaction Networks ◽  
Human Gut ◽  
Statistical Tools ◽  
Human Gut Microbiome ◽  
Network Analyses

Advances in high-throughput sequencing have ushered in a new era of research into the gut microbiome and its role in human health and disease. However, due to the unique characteristics of microbiome survey data, their use for the detection of ecological interaction networks remains a considerable challenge, and a field of active methodological development. In this review, we discuss the landscape of existing statistical and experimental methods for detecting and characterizing microbial interactions, as well as the role that host and environmental metabolic signals play in mediating the behavior of these networks. Numerous statistical tools for microbiome network inference have been developed. Yet due to tool-specific biases, the networks identified by these methods are often discordant, motivating a need for the development of more general tools, the use of ensemble approaches, and the incorporation of prior knowledge into prediction. By elucidating the complex dynamics of the microbial interactome, we will enhance our understanding of the microbiome’s role in disease, more precisely predict the microbiome’s response to perturbation, and inform the development of future therapeutic strategies for microbiome-related disease. Impact statement This review provides a comprehensive description of experimental and statistical tools used for network analyses of the human gut microbiome. Understanding the system dynamics of microbial interactions may lead to the improvement of therapeutic approaches for managing microbiome-associated diseases. Microbiome network inference tools have been developed and applied to both cross-sectional and longitudinal experimental designs, as well as to multi-omic datasets, with the goal of untangling the complex web of microbe-host, microbe-environmental, and metabolism-mediated microbial interactions. The characterization of these interaction networks may lead to a better understanding of the systems dynamics of the human gut microbiome, augmenting our knowledge of the microbiome’s role in human health, and guiding the optimization of effective, precise, and rational therapeutic strategies for managing microbiome-associated disease.

scholarly journals The gut mycobiome: a novel player in chronic liver diseases

2020 ◽  
Author(s):  
Lu Jiang ◽  
Peter Stärkel ◽  
Jian-Gao Fan ◽  
Derrick Eugene Fouts ◽  
Petra Bacher ◽  
...  
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Liver Diseases ◽  
Therapeutic Targets ◽  
Chronic Liver Diseases ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
The Impact ◽  
Potential Use

Abstract The human gut microbiome (bacteria, fungi, viruses, and archaea) is a complex and diverse ecosystem. It plays an important role in human health, but is involved in several intestinal and extraintestinal diseases. Most research to date has focused on the role of bacteria, while studies focusing on fungi (also referred to as “mycobiome” or “fungome”) are still in its infancy. In this review, we focus on the existing literature available about the gut mycobiome with an emphasis on compositional mycobiome changes associated with liver diseases, the impact on pathogenesis of disease, and its potential use as therapeutic targets. We also provide insights into current methodologies of studying mycobiome, and we highlight the interkingdom interactions in the context of disease and how they affect health of the host. Herein, by focusing on the gut mycobiome, this review provides novel insights and directions for liver research.

scholarly journals Establishing What Constitutes a Healthy Human Gut Microbiome: State of the Science, Regulatory Considerations, and Future Directions

2019 ◽  
Vol 149 (11) ◽  
pp. 1882-1895 ◽  
Author(s):  
Michael I McBurney ◽  
Cindy Davis ◽  
Claire M Fraser ◽  
Barbara O Schneeman ◽  
Curtis Huttenhower ◽  
...  
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Interindividual Variation ◽  
Sufficient Evidence ◽  
Human Gut ◽  
Future Studies ◽  
Human Gut Microbiome ◽  
Host Health ◽  
Short And Long Term

ABSTRACTOn December 17, 2018, the North American branch of the International Life Sciences Institute (ILSI North America) convened a workshop “Can We Begin to Define a Healthy Gut Microbiome Through Quantifiable Characteristics?” with >40 invited academic, government, and industry experts in Washington, DC. The workshop objectives were to 1) develop a collective expert assessment of the state of the evidence on the human gut microbiome and associated human health benefits, 2) see if there was sufficient evidence to establish measurable gut microbiome characteristics that could serve as indicators of “health,” 3) identify short- and long-term research needs to fully characterize healthy gut microbiome–host relationships, and 4) publish the findings. Conclusions were as follows: 1) mechanistic links of specific changes in gut microbiome structure with function or markers of human health are not yet established; 2) it is not established if dysbiosis is a cause, consequence, or both of changes in human gut epithelial function and disease; 3) microbiome communities are highly individualized, show a high degree of interindividual variation to perturbation, and tend to be stable over years; 4) the complexity of microbiome-host interactions requires a comprehensive, multidisciplinary research agenda to elucidate relationships between gut microbiome and host health; 5) biomarkers and/or surrogate indicators of host function and pathogenic processes based on the microbiome need to be determined and validated, along with normal ranges, using approaches similar to those used to establish biomarkers and/or surrogate indicators based on host metabolic phenotypes; 6) future studies measuring responses to an exposure or intervention need to combine validated microbiome-related biomarkers and/or surrogate indicators with multiomics characterization of the microbiome; and 7) because static genetic sampling misses important short- and long-term microbiome-related dynamic changes to host health, future studies must be powered to account for inter- and intraindividual variation and should use repeated measures within individuals.

scholarly journals Role of Probiotics in Human Gut Microbiome-Associated Diseases

2019 ◽  
Vol 29 (9) ◽  
pp. 1335-1340 ◽  
Author(s):  
Seon-Kyun Kim ◽  
Robin B. Guevarra ◽  
You-Tae Kim ◽  
Joongi Kwon ◽  
Hyeri Kim ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Associated Diseases

scholarly journals Market Integration Predicts Human Gut Microbiome Attributes across a Gradient of Economic Development

mSystems ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Keaton Stagaman ◽  
Tara J. Cepon-Robins ◽  
Melissa A. Liebert ◽  
Theresa E. Gildner ◽  
Samuel S. Urlacher ◽  
...  
Keyword(s):  
Economic Development ◽  
Gut Microbiome ◽  
Market Integration ◽  
Direct Relationship ◽  
Indigenous Population ◽  
Lifestyle Changes ◽  
Warning Sign ◽  
Human Gut ◽  
Associated Diseases ◽  
Stages Of Economic Development

Previous research has reported differences in the gut microbiome between populations residing in wealthy versus poorer countries, leading to the assertion that lifestyle changes associated with economic development promote changes in the gut microbiome that promote the proliferation of microbiome-associated diseases. However, a direct relationship between economic development and the gut microbiome has not previously been shown. We surveyed the gut microbiomes of a single indigenous population undergoing economic development and found significant associations between features of the gut microbiome and lifestyle changes associated with economic development. These findings suggest that even the earliest stages of economic development can drive changes in the gut microbiome, which may provide a warning sign for the development of microbiome-associated diseases.

Sign in / Sign up

Export Citation Format

Share Document