scholarly journals Synergies of Systems Biology and Synthetic Biology in Human Microbiome Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Bouchra Ezzamouri ◽  
Saeed Shoaie ◽  
Rodrigo Ledesma-Amaro
Keyword(s):  
Synthetic Biology ◽  
Microbial Communities ◽  
System Biology ◽  
Large Scale ◽  
Human Microbiome ◽  
Host Responses ◽  
Future Research ◽  
Host Interactions ◽  
Health And Disease ◽  
Genome Scale

A number of studies have shown that the microbial communities of the human body are integral for the maintenance of human health. Advances in next-generation sequencing have enabled rapid and large-scale quantification of the composition of microbial communities in health and disease. Microorganisms mediate diverse host responses including metabolic pathways and immune responses. Using a system biology approach to further understand the underlying alterations of the microbiota in physiological and pathological states can help reveal potential novel therapeutic and diagnostic interventions within the field of synthetic biology. Tools such as biosensors, memory arrays, and engineered bacteria can rewire the microbiome environment. In this article, we review the computational tools used to study microbiome communities and the current limitations of these methods. We evaluate how genome-scale metabolic models (GEMs) can advance our understanding of the microbe–microbe and microbe–host interactions. Moreover, we present how synergies between these system biology approaches and synthetic biology can be harnessed in human microbiome studies to improve future therapeutics and diagnostics and highlight important knowledge gaps for future research in these rapidly evolving fields.

scholarly journals The oral microbiome

2017 ◽  
Vol 1 (4) ◽  
pp. 287-296 ◽  
Author(s):  
Liam P. Shaw ◽  
Andrew M. Smith ◽  
Adam P. Roberts
Keyword(s):  
Human Microbiome ◽  
Oral Microbiome ◽  
Core Microbiome ◽  
Individual Level ◽  
Host Interactions ◽  
Paradoxical Situation ◽  
Health And Disease ◽  
Stable Core ◽  
The Individual ◽  
Conserved Core

The human microbiome is receiving a great deal of attention as its role in health and disease becomes ever more apparent. The oral microbiome, perhaps due to the ease with which we can obtain samples, is arguably the most well-studied human microbiome to date. It is obvious, however, that we have only just begun to scratch the surface of the complex bacterial and bacterial–host interactions within this complex community. Here, we describe the factors which are known to influence the development of the seemingly globally conserved, core, oral microbiome and those which are likely to be responsible for the observed differences at the individual level. We discuss the paradoxical situation of maintaining a stable core microbiome which is at the same time incredibly resilient and adaptable to many different stresses encountered in the open environment of the oral cavity. Finally, we explore the interactions of the oral microbiome with the host and discuss the interactions underlying human health and disease.

scholarly journals Metabolic multistability and hysteresis in a model aerobe-anaerobe microbiome community

2020 ◽  
Vol 6 (33) ◽  
pp. eaba0353 ◽  
Author(s):  
Tahmineh Khazaei ◽  
Rory L. Williams ◽  
Said R. Bogatyrev ◽  
John C. Doyle ◽  
Christopher S. Henry ◽  
...  
Keyword(s):  
Conceptual Understanding ◽  
Human Microbiome ◽  
Bacterial Overgrowth ◽  
Small Intestinal Bacterial Overgrowth ◽  
Stable States ◽  
Intestinal Bacterial Overgrowth ◽  
Health And Disease ◽  
Small Intestinal ◽  
Genome Scale ◽  
The Impact

Major changes in the microbiome are associated with health and disease. Some microbiome states persist despite seemingly unfavorable conditions, such as the proliferation of aerobe-anaerobe communities in oxygen-exposed environments in wound infections or small intestinal bacterial overgrowth. Mechanisms underlying transitions into and persistence of these states remain unclear. Using two microbial taxa relevant to the human microbiome, we combine genome-scale mathematical modeling, bioreactor experiments, transcriptomics, and dynamical systems theory to show that multistability and hysteresis (MSH) is a mechanism describing the shift from an aerobe-dominated state to a resilient, paradoxically persistent aerobe-anaerobe state. We examine the impact of changing oxygen and nutrient regimes and identify changes in metabolism and gene expression that lead to MSH and associated multi-stable states. In such systems, conceptual causation-correlation connections break and MSH must be used for analysis. Using MSH to analyze microbiome dynamics will improve our conceptual understanding of stability of microbiome states and transitions between states.

scholarly journals Genome binning of viral entities from bulk metagenomics data

2021 ◽  
Author(s):  
Joachim Johansen ◽  
Damian R Plichta ◽  
Jakob Nybo Nissen ◽  
Marie Louise Jespersen ◽  
Shiraz A Shah ◽  
...  
Keyword(s):  
Deep Learning ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Gastrointestinal Diseases ◽  
Human Gut ◽  
Viral Genomes ◽  
Host Interactions ◽  
Metagenomics Data ◽  
Health And Disease ◽  
Viral Host Interactions

Despite the accelerating number of uncultivated virus sequences discovered in metagenomics and their apparent importance for health and disease, the human gut virome and its interactions with bacteria in the gastrointestinal are not well understood. In addition, a paucity of whole-virome datasets from subjects with gastrointestinal diseases is preventing a deeper understanding of the virome role in disease and in gastrointestinal ecology as a whole. By combining a deep-learning based metagenomics binning algorithm with paired metagenome and metavirome datasets we developed the Phages from Metagenomics Binning (PHAMB) approach for binning thousands of viral genomes directly from bulk metagenomics data. Simultaneously our methodology enables clustering of viral genomes into accurate taxonomic viral populations. We applied this methodology on the Human Microbiome Project 2 (HMP2) cohort and recovered 6,077 HQ genomes from 1,024 viral populations and explored viral-host interactions. We show that binning can be advantageously applied to existing and future metagenomes to illuminate viral ecological dynamics with other microbiome constituents.

scholarly journals TaxiBGC: a Taxonomy-guided Approach for the Identification of Experimentally Verified Microbial Biosynthetic Gene Clusters in Shotgun Metagenomic Data

2021 ◽  
Author(s):  
Utpal Bakshi ◽  
Vinod K Gupta ◽  
Aileen R Lee ◽  
John M Davis ◽  
Sriram Chandrasekaran ◽  
...  
Keyword(s):  
Large Scale ◽  
Human Microbiome ◽  
Gene Clusters ◽  
Human Microbiome Project ◽  
Metagenomic Data ◽  
Biosynthetic Gene ◽  
Case Control Studies ◽  
Biosynthetic Gene Clusters ◽  
Host Interactions ◽  
Microbiome Data

Biosynthetic gene clusters (BGCs) in microbial genomes encode for the production of bioactive secondary metabolites (SMs). Given the well-recognized importance of SMs in microbe-microbe and microbe-host interactions, the large-scale identification of BGCs from microbial metagenomes could offer novel functional insights into complex chemical ecology. Despite recent progress, currently available tools for predicting BGCs from shotgun metagenomes have several limitations, including the need for computationally demanding read-assembly and prediction of a narrow breadth of BGC classes. To overcome these limitations, we developed TaxiBGC (Taxonomy-guided Identification of Biosynthetic Gene Clusters), a computational pipeline for identifying experimentally verified BGCs in shotgun metagenomes by first pinpointing the microbial species likely to produce them. We show that our species-centric approach was able to identify BGCs in simulated metagenomes more accurately than by solely detecting BGC genes. By applying TaxiBGC on 5,423 metagenomes from the Human Microbiome Project and various case-control studies, we identified distinct BGC signatures of major human body sites and candidate stool-borne biomarkers for multiple diseases, including inflammatory bowel disease, colorectal cancer, and psychiatric disorders. In all, TaxiBGC demonstrates a significant advantage over existing techniques for systematically characterizing BGCs and inferring their SMs from microbiome data.

scholarly journals The Mouse Intestinal Bacterial Collection (miBC) provides host-specific insight into cultured diversity and functional potential of the gut microbiota

2016 ◽  
Vol 1 (10) ◽  
Author(s):  
Ilias Lagkouvardos ◽  
Rüdiger Pukall ◽  
Birte Abt ◽  
Bärbel U. Foesel ◽  
Jan P. Meier-Kolthoff ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Bacteria ◽  
Future Research ◽  
Bacterial Strains ◽  
Host Interactions ◽  
Functional Potential ◽  
Health And Disease ◽  
Mouse Intestine ◽  
Reference Strains ◽  
Insight Into

Abstract Intestinal bacteria influence mammalian physiology, but many types of bacteria are still uncharacterized. Moreover, reference strains of mouse gut bacteria are not easily available, although mouse models are extensively used in medical research. These are major limitations for the investigation of intestinal microbiomes and their interactions with diet and host. It is thus important to study in detail the diversity and functions of gut microbiota members, including those colonizing the mouse intestine. To address these issues, we aimed at establishing the Mouse Intestinal Bacterial Collection (miBC), a public repository of bacterial strains and associated genomes from the mouse gut, and studied host-specificity of colonization and sequence-based relevance of the resource. The collection includes several strains representing novel species, genera and even one family. Genomic analyses showed that certain species are specific to the mouse intestine and that a minimal consortium of 18 strains covered 50–75% of the known functional potential of metagenomes. The present work will sustain future research on microbiota–host interactions in health and disease, as it will facilitate targeted colonization and molecular studies. The resource is available at www.dsmz.de/miBC.

scholarly journals From Structure to Function: the Ecology of Host-Associated Microbial Communities

2010 ◽  
Vol 74 (3) ◽  
pp. 453-476 ◽  
Author(s):  
Courtney J. Robinson ◽  
Brendan J. M. Bohannan ◽  
Vincent B. Young
Keyword(s):  
Community Structure ◽  
Microbial Communities ◽  
Human Microbiome ◽  
Structure And Function ◽  
Future Directions ◽  
Human Microbiota ◽  
Health And Disease ◽  
Indigenous Microbiota ◽  
And Function

SUMMARY In the past several years, we have witnessed an increased interest in understanding the structure and function of the indigenous microbiota that inhabits the human body. It is hoped that this will yield novel insight into the role of these complex microbial communities in human health and disease. What is less appreciated is that this recent activity owes a great deal to the pioneering efforts of microbial ecologists who have been studying communities in non-host-associated environments. Interactions between environmental microbiologists and human microbiota researchers have already contributed to advances in our understanding of the human microbiome. We review the work that has led to these recent advances and illustrate some of the possible future directions for continued collaboration between these groups of researchers. We discuss how the application of ecological theory to the human-associated microbiota can lead us past descriptions of community structure and toward an understanding of the functions of the human microbiota. Such an approach may lead to a shift in the prevention and treatment of human diseases that involves conservation or restoration of the normal community structure and function of the host-associated microbiota.

scholarly journals Metabolic multi-stability and hysteresis in a model aerobe-anaerobe microbiome community

2020 ◽  
Author(s):  
Tahmineh Khazaei ◽  
Rory L. Williams ◽  
Said R. Bogatyrev ◽  
John C. Doyle ◽  
Christopher S. Henry ◽  
...  
Keyword(s):  
Human Microbiome ◽  
Bacterial Overgrowth ◽  
Small Intestinal Bacterial Overgrowth ◽  
Intestinal Bacterial Overgrowth ◽  
Conceptual Connection ◽  
Health And Disease ◽  
Small Intestinal ◽  
The Stability ◽  
Genome Scale ◽  
The Impact

AbstractChanges in the composition of the human microbiome are associated with health and disease. Some microbiome states persist in seemingly unfavorable conditions, e.g., the proliferation of aerobe-anaerobe communities in oxygen-exposed environments in wounds or small intestinal bacterial overgrowth. However, it remains unclear how different stable microbiome states can exist under the same conditions, or why some states persist under seemingly unfavorable conditions. Here, using two microbes relevant to the human microbiome, we combine genome-scale mathematical modeling, bioreactor experiments, transcriptomics, and dynamical systems theory, to show that multi-stability and hysteresis (MSH) is a mechanism that can describe the shift from an aerobe-dominated state to a resilient, paradoxically persistent aerobe-anaerobe state. We examine the impact of changing oxygen and nutrient regimes and identify factors, including changes in metabolism and gene expression, that lead to MSH. When analyzing the transitions between the two states in this system, the familiar conceptual connection between causation and correlation is broken and MSH must be used to interpret the dynamics. Using MSH to analyze microbiome dynamics will improve our conceptual understanding of the stability of microbiome states and the transitions among microbiome states.One sentence summaryMulti-stability and hysteresis (MSH) is a potential mechanism to describe shifts to and persistence of aerobe-anaerobe communities in the microbiome.

scholarly journals AGORA2: Large scale reconstruction of the microbiome highlights wide-spread drug-metabolising capacities

2020 ◽  
Author(s):  
Almut Heinken ◽  
Geeta Acharya ◽  
Dmitry A. Ravcheev ◽  
Johannes Hertel ◽  
Malgorzata Nyga ◽  
...  
Keyword(s):  
Large Scale ◽  
Human Microbiome ◽  
Metabolic Modelling ◽  
Drug Degradation ◽  
Literature Searches ◽  
Pairwise Models ◽  
The Individual ◽  
Colorectal Cancer Patients ◽  
Genome Scale ◽  
Drug Activation

AbstractThe human microbiome influences the efficacy and safety of a wide variety of commonly prescribed drugs, yet comprehensive systems-level approaches to interrogate drug-microbiome interactions are lacking. Here, we present a computational resource of human microbial genome-scale reconstructions, deemed AGORA2, which accounts for 7,206 strains, includes microbial drug degradation and biotransformation, and was extensively curated based on comparative genomics and literature searches. AGORA2 serves as a knowledge base for the human microbiome and as a metabolic modelling resource. We demonstrate the latter by mechanistically modelling microbial drug metabolism capabilities in single strains and pairwise models. Moreover, we predict the individual-specific drug conversion potential in a cohort of 616 colorectal cancer patients and controls. This analysis reveals that some drug activation capabilities are present in only a subset of individuals, moreover, drug conversion potential correlate with clinical parameters. Thus, AGORA2 paves the way towards personalised, predictive analysis of host-drug-microbiome interactions.

The Gut Microbiome and Pediatric Cancer: Current Research and Gaps in Knowledge

2019 ◽  
Vol 2019 (54) ◽  
pp. 169-173 ◽  
Author(s):  
Roma Bhuta ◽  
Michael Nieder ◽  
Tracey Jubelirer ◽  
Elena J Ladas
Keyword(s):  
Pediatric Cancer ◽  
Gut Microbiome ◽  
Immune Modulation ◽  
Human Microbiome ◽  
Disease Diagnosis ◽  
Future Research ◽  
Cancer Pathogenesis ◽  
Health And Disease ◽  
Clinically Significant

Abstract The human microbiome consists of trillions of microbial cells that interact with one another and the human host to play a clinically significant role in health and disease. Gut microbial changes have been identified in cancer pathogenesis, at disease diagnosis, during therapy, and even long after completion of treatment. Alterations in the gut microbiome have been linked to treatment-related toxicity and potential long-term morbidity and mortality in children with cancer. Such alterations are plausible given immune modulation due to disease as well as exposure to cytotoxic chemotherapy, infections, and antibiotics. The following review presents our current scientific understanding on the role of the gut microbiome in pediatric cancer, identifies gaps in knowledge, and suggests future research goals.

scholarly journals GutCyc: a Multi-Study Collection of Human Gut Microbiome Metabolic Models

2016 ◽  
Author(s):  
Aria S. Hahn ◽  
Tomer Altman ◽  
Kishori M. Konwar ◽  
Niels W. Hanson ◽  
Dongjae Kim ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Large Scale ◽  
High Throughput Sequencing ◽  
Human Microbiome ◽  
Therapeutic Interventions ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Disease States ◽  
Health And Disease ◽  
Inflammatory Bowel

AbstractAdvances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available. However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, we developed GUTCYC, a compendium of environmental pathway genome databases constructed from 418 assembled human microbiome datasets using METAPATHWAYS, enabling reproducible functional metagenomic annotation. We also generated metabolic network reconstructions for each metagenome using the PATHWAY TOOLS software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GUTCYC provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn’s disease, and type 2 diabetes. GUTCYC data products are searchable online, or may be downloaded and explored locally using METAPATHWAYS and PATHWAY TOOLS.

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