scholarly journals A Computational Method to Dissect Colonization Resistance of the Gut Microbiota against Pathogens

2022 ◽  
Author(s):  
Shanlin Ke ◽  
Yandong Xiao ◽  
Scott T. Weiss ◽  
Xinhua Chen ◽  
Ciaran P. Kelly ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Rational Design ◽  
Computational Method ◽  
Colonization Resistance ◽  
Gut Microbes ◽  
Population Dynamics Model ◽  
Microbiome Research ◽  
Enteric Infections ◽  
Health And Disease ◽  
Microbiome Data

The indigenous gut microbes have co-evolved with their hosts for millions of years. Those gut microbes play a crucial role in host health and disease. In particular, they protect the host against incursion by exogenous and often harmful microorganisms, a mechanism known as colonization resistance (CR). Yet, identifying the exact microbes responsible for the gut microbiota-mediated CR against a particular pathogen remains a fundamental challenge in microbiome research. Here, we develop a computational method --- Generalized Microbe-Phenotype Triangulation (GMPT) to systematically identify causal microbes that directly influence the microbiota-mediated CR against a pathogen. We systematically validate GMPT using a classical population dynamics model in community ecology, and then apply it to microbiome data from two mouse studies on C. difficile infection. The developed method will not only significantly advance our understanding of CR mechanisms but also pave the way for the rational design of microbiome-based therapies for preventing and treating enteric infections.

scholarly journals BOARD INVITED REVIEW: The pig microbiota and the potential for harnessing the power of the microbiome to improve growth and health1

2019 ◽  
Vol 97 (9) ◽  
pp. 3741-3757 ◽  
Author(s):  
Nirosh D Aluthge ◽  
Dana M Van Sambeek ◽  
Erin E Carney-Hinkle ◽  
Yanshuo S Li ◽  
Samodha C Fernando ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Therapeutic Potential ◽  
Animal Health ◽  
Microbial Colonization ◽  
Critical Importance ◽  
Specific Host ◽  
Microbiome Research ◽  
Health And Disease ◽  
The Impact

Abstract A variety of microorganisms inhabit the gastrointestinal tract of animals including bacteria, archaea, fungi, protozoa, and viruses. Pioneers in gut microbiology have stressed the critical importance of diet:microbe interactions and how these interactions may contribute to health status. As scientists have overcome the limitations of culture-based microbiology, the importance of these interactions has become more clear even to the extent that the gut microbiota has emerged as an important immunologic and metabolic organ. Recent advances in metagenomics and metabolomics have helped scientists to demonstrate that interactions among the diet, the gut microbiota, and the host to have profound effects on animal health and disease. However, although scientists have now accumulated a great deal of data with respect to what organisms comprise the gastrointestinal landscape, there is a need to look more closely at causative effects of the microbiome. The objective of this review is intended to provide: 1) a review of what is currently known with respect to the dynamics of microbial colonization of the porcine gastrointestinal tract; 2) a review of the impact of nutrient:microbe effects on growth and health; 3) examples of the therapeutic potential of prebiotics, probiotics, and synbiotics; and 4) a discussion about what the future holds with respect to microbiome research opportunities and challenges. Taken together, by considering what is currently known in the four aforementioned areas, our overarching goal is to set the stage for narrowing the path towards discovering how the porcine gut microbiota (individually and collectively) may affect specific host phenotypes.

scholarly journals Gut Microbiota and Host Metabolism: From Proof of Concept to Therapeutic Intervention

2021 ◽  
Vol 9 (6) ◽  
pp. 1302
Author(s):  
Patrice D. Cani ◽  
Emilie Moens de Hase ◽  
Matthias Van Hul
Keyword(s):  
Gut Microbiota ◽  
Research Field ◽  
Proof Of Concept ◽  
Clinical Implementation ◽  
Science Area ◽  
Microbiome Research ◽  
Fast Pace ◽  
Health And Disease ◽  
Underlying Mechanisms ◽  
Host Metabolism

The field of the gut microbiota is still a relatively young science area, yet many studies have already highlighted the translational potential of microbiome research in the context of human health and disease. However, like in many new fields, discoveries are occurring at a fast pace and have provided new hope for the development of novel clinical applications in many different medical conditions, not in the least in metabolic disorders. This rapid progress has left the field vulnerable to premature claims, misconceptions and criticism, both from within and outside the sector. Tackling these issues requires a broad collaborative effort within the research field and is only possible by acknowledging the difficulties and challenges that are faced and that are currently hindering clinical implementation. These issues include: the primarily descriptive nature of evidence, methodological concerns, disagreements in analysis techniques, lack of causality, and a rather limited molecular-based understanding of underlying mechanisms. In this review, we discuss various studies and models that helped identifying the microbiota as an attractive tool or target for developing various translational applications. We also discuss some of the limitations and try to clarify some common misconceptions that are still prevalent in the field.

Effects of Antibiotics on Gut Microbiota

2016 ◽  
Vol 34 (3) ◽  
pp. 260-268 ◽  
Author(s):  
Kathleen Lange ◽  
Martin Buerger ◽  
Andreas Stallmach ◽  
Tony Bruns
Keyword(s):  
Energy Metabolism ◽  
Antimicrobial Resistance ◽  
Gut Microbiota ◽  
External Perturbation ◽  
Colonization Resistance ◽  
Short Term ◽  
Common Features ◽  
Health And Disease ◽  
Immune Pathways

The gut microbiota influences essential human functions including digestion, energy metabolism, and inflammation by modulating multiple endocrine, neural, and immune pathways of the host. Its composition and complexity varies markedly across individuals and across different sites of the gut, but provides a certain level of resilience against external perturbation. Short-term antibiotic treatment is able to shift the gut microbiota to long-term alternative dysbiotic states, which may promote the development and aggravation of disease. Common features of post-antibiotic dysbiosis include a loss of taxonomic and functional diversity combined with reduced colonization resistance against invading pathogens, which harbors the danger of antimicrobial resistance. This review summarizes the antibiotic-related changes of the gut microbiota and potential consequences in health and disease.

scholarly journals Gut Microbiota and Colonization Resistance against Bacterial Enteric Infection

2019 ◽  
Vol 83 (3) ◽  
Author(s):  
Q. R. Ducarmon ◽  
R. D. Zwittink ◽  
B. V. H. Hornung ◽  
W. van Schaik ◽  
V. B. Young ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Current Knowledge ◽  
Shigella Flexneri ◽  
Enteric Infection ◽  
Nutrient Competition ◽  
Colonization Resistance ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Serovar Typhimurium ◽  
Enteric Infections

SUMMARYThe gut microbiome is critical in providing resistance against colonization by exogenous microorganisms. The mechanisms via which the gut microbiota provide colonization resistance (CR) have not been fully elucidated, but they include secretion of antimicrobial products, nutrient competition, support of gut barrier integrity, and bacteriophage deployment. However, bacterial enteric infections are an important cause of disease globally, indicating that microbiota-mediated CR can be disturbed and become ineffective. Changes in microbiota composition, and potential subsequent disruption of CR, can be caused by various drugs, such as antibiotics, proton pump inhibitors, antidiabetics, and antipsychotics, thereby providing opportunities for exogenous pathogens to colonize the gut and ultimately cause infection. In addition, the most prevalent bacterial enteropathogens, includingClostridioides difficile,Salmonella entericaserovar Typhimurium, enterohemorrhagicEscherichia coli,Shigella flexneri,Campylobacter jejuni,Vibrio cholerae,Yersinia enterocolitica, andListeria monocytogenes, can employ a wide array of mechanisms to overcome colonization resistance. This review aims to summarize current knowledge on how the gut microbiota can mediate colonization resistance against bacterial enteric infection and on how bacterial enteropathogens can overcome this resistance.

scholarly journals Ecophylogenetics Clarifies the Evolutionary Association between Mammals and Their Gut Microbiota

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Christopher A. Gaulke ◽  
Holly K. Arnold ◽  
Ian R. Humphreys ◽  
Steven W. Kembel ◽  
James P. O’Dwyer ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Mammalian Species ◽  
Mammalian Evolution ◽  
Gut Microbes ◽  
Core Set ◽  
Shared Ancestry ◽  
Microbial Taxonomy ◽  
Microbiome Data

ABSTRACTOur knowledge of how the gut microbiome relates to mammalian evolution benefits from the identification of gut microbial taxa that are unexpectedly prevalent or unexpectedly conserved across mammals. Such taxa enable experimental determination of the traits needed for such microbes to succeed as gut generalists, as well as those traits that impact mammalian fitness. However, the punctuated resolution of microbial taxonomy may limit our ability to detect conserved gut microbes, especially in cases in which broadly related microbial lineages possess shared traits that drive their apparent ubiquity across mammals. To advance the discovery of conserved mammalian gut microbes, we developed a novel ecophylogenetic approach to taxonomy that groups microbes into taxonomic units based on their shared ancestry and their common distribution across mammals. Applying this approach to previously generated gut microbiome data uncovered monophyletic clades of gut bacteria that are conserved across mammals. It also resolved microbial clades exclusive to and conserved among particular mammalian lineages. Conserved clades often manifest phylogenetic patterns, such as cophylogeny with their host, that indicate that they are subject to selective processes, such as host filtering. Moreover, this analysis identified variation in the rate at which mammals acquire or lose conserved microbial clades and resolved a human-accelerated loss of conserved clades. Collectively, the data from this study reveal mammalian gut microbiota that possess traits linked to mammalian phylogeny, point to the existence of a core set of microbes that comprise the mammalian gut microbiome, and clarify potential evolutionary or ecologic mechanisms driving the gut microbiome’s diversification throughout mammalian evolution.IMPORTANCEOur understanding of mammalian evolution has become microbiome-aware. While emerging research links mammalian biodiversity and the gut microbiome, we lack insight into which microbes potentially impact mammalian evolution. Microbes common to diverse mammalian species may be strong candidates, as their absence in the gut may affect how the microbiome functionally contributes to mammalian physiology to adversely affect fitness. Identifying such conserved gut microbes is thus important to ultimately assessing the microbiome’s potential role in mammalian evolution. To advance their discovery, we developed an approach that identifies ancestrally related groups of microbes that distribute across mammals in a way that indicates their collective conservation. These conserved clades are presumed to have evolved a trait in their ancestor that matters to their distribution across mammals and which has been retained among clade members. We found not only that such clades do exist among mammals but also that they appear to be subject to natural selection and characterize human evolution.

scholarly journals The Microbiota-Gut-Brain Axis in Health and Disease and Its Implications for Translational Research

2021 ◽  
Vol 15 ◽  
Author(s):  
Melanie Anna Schächtle ◽  
Stephan Patrick Rosshart
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nervous System ◽  
Gut Microbiota ◽  
Translational Research ◽  
Biologically Active ◽  
Brain Physiology ◽  
Microbiome Research ◽  
Health And Disease ◽  
The Impact

Over the past decades, microbiome research has evolved rapidly and became a hot topic in basic, preclinical and clinical research, for the pharmaceutical industry and for the general public. With the help of new high-throughput sequencing technologies tremendous progress has been made in the characterization of host-microbiota interactions identifying the microbiome as a major factor shaping mammalian physiology. This development also led to the discovery of the gut-brain axis as the crucial connection between gut microbiota and the nervous system. Consequently, a rapidly growing body of evidence emerged suggesting that the commensal gut microbiota plays a vital role in brain physiology. Moreover, it became evident that the communication along this microbiota-gut-brain axis is bidirectional and primarily mediated by biologically active microbial molecules and metabolites. Further, intestinal dysbiosis leading to changes in the bidirectional relationship between gut microbiota and the nervous system was linked to the pathogenesis of several psychiatric and neurological disorders. Here, we discuss the impact of the gut microbiota on the brain in health and disease, specifically as regards to neuronal homeostasis, development and normal aging as well as their role in neurological diseases of the highest socioeconomic burden such as Alzheimer’s disease and stroke. Subsequently, we utilize Alzheimer’s disease and stroke to examine the translational research value of current mouse models in the spotlight of microbiome research. Finally, we propose future strategies on how we could conduct translational microbiome research in the field of neuroscience that may lead to the identification of novel treatments for human diseases.

The gut-brain axis: microglia in the spotlight

Neuroforum ◽  
2019 ◽  
Vol 25 (3) ◽  
pp. 205-212 ◽  
Author(s):  
Charlotte Mezö ◽  
Omar Mossad ◽  
Daniel Erny ◽  
Thomas Blank
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gut Microbiota ◽  
Immune Cells ◽  
Brain Functions ◽  
Microbiome Research ◽  
The Central Nervous System ◽  
Health And Disease ◽  
The Brain

Summary Microbiome research has grown significantly in the last decade, highlighting manifold implications of the microbiota to the host’s health. The gut microbiota is connected to the brain through several avenues that allow their interaction. Thus, recent studies have attemtpted to characterize these connections and enhance our understanding of the so called ‘gut-brain-axis’. Microglia, the central nervous system resident macrophages, are crucial for the proper development and maintenance of brain functions. As immune cells, they are in the spotlight for relaying signals between the microbiota and cells of the brain. In this review, we contemplate on interactions between the gut microbiota and microglia, and their influence on brain functions in health and disease.

scholarly journals Mechanism of the Gut Microbiota Colonization Resistance and Enteric Pathogen Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Israr Khan ◽  
Yanrui Bai ◽  
Lajia Zha ◽  
Naeem Ullah ◽  
Habib Ullah ◽  
...  
Keyword(s):  
Microbial Community ◽  
Gut Microbiota ◽  
Critical Role ◽  
Complex Interaction ◽  
Enteric Pathogens ◽  
Nutrient Competition ◽  
Colonization Resistance ◽  
Enteric Infections ◽  
Metabolic Interactions ◽  
Gut Microbial Community

The mammalian gut microbial community, known as the gut microbiota, comprises trillions of bacteria, which co-evolved with the host and has an important role in a variety of host functions that include nutrient acquisition, metabolism, and immunity development, and more importantly, it plays a critical role in the protection of the host from enteric infections associated with exogenous pathogens or indigenous pathobiont outgrowth that may result from healthy gut microbial community disruption. Microbiota evolves complex mechanisms to restrain pathogen growth, which included nutrient competition, competitive metabolic interactions, niche exclusion, and induction of host immune response, which are collectively termed colonization resistance. On the other hand, pathogens have also developed counterstrategies to expand their population and enhance their virulence to cope with the gut microbiota colonization resistance and cause infection. This review summarizes the available literature on the complex relationship occurring between the intestinal microbiota and enteric pathogens, describing how the gut microbiota can mediate colonization resistance against bacterial enteric infections and how bacterial enteropathogens can overcome this resistance as well as how the understanding of this complex interaction can inform future therapies against infectious diseases.

scholarly journals Next Generation Microbiome Research: Identification of Keystone Species in the Metabolic Regulation of Host-Gut Microbiota Interplay

2021 ◽  
Vol 9 ◽  
Author(s):  
Héloïse Tudela ◽  
Sandrine P. Claus ◽  
Maya Saleh
Keyword(s):  
Gut Microbiota ◽  
Metabolic Regulation ◽  
Keystone Species ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Nutrient Metabolism ◽  
Major Step ◽  
Microbiome Research ◽  
Health And Disease

The community of the diverse microorganisms residing in the gastrointestinal tract, known as the gut microbiota, is exceedingly being studied for its impact on health and disease. This community plays a major role in nutrient metabolism, maintenance of the intestinal epithelial barrier but also in local and systemic immunomodulation. A dysbiosis of the gut microbiota, characterized by an unbalanced microbial ecology, often leads to a loss of essential functions that may be associated with proinflammatory conditions. Specifically, some key microbes that are depleted in dysbiotic ecosystems, called keystone species, carry unique functions that are essential for the balance of the microbiota. In this review, we discuss current understanding of reported keystone species and their proposed functions in health. We also elaborate on current and future bioinformatics tools needed to identify missing functions in the gut carried by keystone species. We propose that the identification of such keystone species functions is a major step for the understanding of microbiome dynamics in disease and toward the development of microbiome-based therapeutics.

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