Microbiota as Therapeutic Targets

2016 ◽  
Vol 34 (5) ◽  
pp. 558-565 ◽  
Author(s):  
Ramnik J. Xavier
Keyword(s):  
Gastrointestinal Tract ◽  
Microbial Communities ◽  
Association Studies ◽  
Microbial Community Composition ◽  
Great Promise ◽  
Host Immune System ◽  
Genome Wide Association Studies ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
And Function

Background: Inflammatory bowel disease (IBD) represents a family of diseases including Crohn's disease and ulcerative colitis. IBD has garnered significant attention in recent years due to successes in 2 areas of basic science: complex human genetics and host-microbe interactions. Advances in understanding the genetics of IBD, mainly driven by genome-wide association studies, have identified more than 160 genetic loci that modulate the risk of disease. Notably, several of these genes have pointed to alterations in host-microbe interactions as being critical factors in pathogenesis. Investigations into the microbial communities of the gastrointestinal tract (or the ‘gut microbiome') in IBD have yielded important insights into several aspects of interactions between microbiota and the host immune system, including how alterations to microbial community composition and function have important consequences for immune homeostasis. Key Messages: The anatomy of the gastrointestinal tract plays a role in defining not only intestinal function, but also the microbial ecosystem that lives within the gut. Careful investigations into the composition and function of these microbial communities have suggested that patients with IBD have an imbalance in their gut microbiota, termed dysbiosis. These studies, as well as studies using samples from healthy individuals, have begun to uncover mechanisms of crosstalk between particular microbes (and microbial products) and immunomodulatory pathways, alterations which may drive immune diseases such as IBD. Conclusions: Investigations into the role of the microbiome in IBD have provided important clues to potential pathogenic mechanisms. Harnessing this knowledge to develop therapeutics and identify biomarkers is currently a major translational goal, holding great promise for clinically meaningful progress.

scholarly journals Parallel changes in gut microbiome composition and function in parallel local adaptation and speciation

2019 ◽  
Author(s):  
Diana J. Rennison ◽  
Seth M. Rudman ◽  
Dolph Schluter
Keyword(s):  
Microbial Communities ◽  
Local Adaptation ◽  
Biotic Interactions ◽  
Ecological Speciation ◽  
Microbiome Composition ◽  
Interacting Species ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
And Function ◽  
Host Evolution

AbstractThe processes of local adaptation and ecological speciation are often strongly shaped by biotic interactions such as competition and predation. One of the strongest lines of evidence that biotic interactions drive evolution comes from repeated divergence of lineages in association with repeated changes in the community of interacting species. Yet, relatively little is known about the repeatability of changes in gut microbial communities and their role in adaptation and divergence of host populations in nature. Here we utilize three cases of rapid, parallel adaptation and speciation in freshwater threespine stickleback to test for parallel changes in associated gut microbiomes. We find that features of the gut microbial communities have shifted repeatedly in the same direction in association with parallel divergence and speciation of stickleback hosts. These results suggest that changes to gut microbiomes can occur rapidly and predictably in conjunction with host evolution, and that host-microbe interactions might play an important role in host adaptation and diversification.

scholarly journals Inter-species microbiota transplantation recapitulates microbial acquisition and persistence in mosquitoes

2021 ◽  
Author(s):  
Kerri L. Coon ◽  
Shivanand Hegde ◽  
Grant L. Hughes
Keyword(s):  
Life Cycle ◽  
Microbial Communities ◽  
Human Pathogens ◽  
Future Studies ◽  
Larval Stages ◽  
Microbial Structures ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
And Function ◽  
Microbiota Diversity

AbstractBackgroundMosquitoes harbor microbial communities that play important roles in their growth, survival, reproduction, and ability to transmit human pathogens. Microbiome transplantation approaches are often used to study host-microbe interactions and identify microbial taxa and assemblages associated with health or disease. However, no such approaches have been developed to manipulate the microbiota of mosquitoes.ResultsHere, we developed an approach to transfer entire microbial communities between mosquito cohorts. We undertook transfers between (Culex quinquefasciatus to Aedes aegypti) and within (Ae. aegypti to Ae. aegypti) species to validate the approach and determine the number of mosquitoes required to prepare donor microbiota. After the transfer, we monitored mosquito development and microbiota dynamics throughout the life cycle. Typical holometabolous lifestyle-related microbiota structures were observed, with higher dynamics of microbial structures in larval stages, including the larval water, and less diversity in adults. Microbiota diversity in recipient adults was also more similar to the microbiota diversity in donor adults.ConclusionsThis study provides the first evidence for successful microbiome transplantation in mosquitoes. Our results highlight the value of such methods for studying mosquito-microbe interactions and lay the foundation for future studies to elucidate the factors underlying microbiota acquisition, assembly, and function in mosquitoes under controlled conditions.

scholarly journals Genome-wide association studies on the phyllosphere microbiome: Embracing complexity in host-microbe interactions

2019 ◽  
Vol 97 (1) ◽  
pp. 164-181 ◽  
Author(s):  
Kathleen Beilsmith ◽  
Manus P.M. Thoen ◽  
Benjamin Brachi ◽  
Andrew D. Gloss ◽  
Mohammad H. Khan ◽  
...  
Keyword(s):  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Microbe Interactions ◽  
Host Microbe Interactions

scholarly journals Parallel changes in gut microbiome composition and function during colonization, local adaptation and ecological speciation

2019 ◽  
Vol 286 (1916) ◽  
pp. 20191911 ◽  
Author(s):  
Diana J. Rennison ◽  
Seth M. Rudman ◽  
Dolph Schluter
Keyword(s):  
Microbial Communities ◽  
Local Adaptation ◽  
Biotic Interactions ◽  
Ecological Speciation ◽  
Microbiome Composition ◽  
Interacting Species ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
And Function ◽  
Host Evolution

The processes of local adaptation and ecological speciation are often strongly shaped by biotic interactions such as competition and predation. One of the strongest lines of evidence that biotic interactions drive evolution comes from the repeated divergence of lineages in association with repeated changes in the community of interacting species. Yet relatively little is known about the repeatability of changes in gut microbial communities and their role in adaptation and divergence of host populations in nature. Here we use three cases of rapid, parallel adaptation and speciation in freshwater threespine stickleback to test for parallel changes in associated gut microbiomes. We find that features of the gut microbial communities have shifted repeatedly in the same direction in association with parallel divergence and speciation of stickleback hosts. These results suggest that changes to gut microbiomes can occur rapidly and predictably in conjunction with host evolution, and that host–microbe interactions might play an important role in host adaptation and diversification.

scholarly journals A gene co-association network regulating gut microbial communities in a Duroc pig population

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Antonio Reverter ◽  
Maria Ballester ◽  
Pamela A. Alexandre ◽  
Emilio Mármol-Sánchez ◽  
Antoni Dalmau ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Candidate Genes ◽  
Relative Abundance ◽  
Association Studies ◽  
Single Gene ◽  
Host Genome ◽  
Genome Wide Association Studies ◽  
Vaccine Response ◽  
Microbiome Composition ◽  
Host Genetic

Abstract Background Analyses of gut microbiome composition in livestock species have shown its potential to contribute to the regulation of complex phenotypes. However, little is known about the host genetic control over the gut microbial communities. In pigs, previous studies are based on classical “single-gene-single-trait” approaches and have evaluated the role of host genome controlling gut prokaryote and eukaryote communities separately. Results In order to determine the ability of the host genome to control the diversity and composition of microbial communities in healthy pigs, we undertook genome-wide association studies (GWAS) for 39 microbial phenotypes that included 2 diversity indexes, and the relative abundance of 31 bacterial and six commensal protist genera in 390 pigs genotyped for 70 K SNPs. The GWAS results were processed through a 3-step analytical pipeline comprised of (1) association weight matrix; (2) regulatory impact factor; and (3) partial correlation and information theory. The inferred gene regulatory network comprised 3561 genes (within a 5 kb distance from a relevant SNP–P < 0.05) and 738,913 connections (SNP-to-SNP co-associations). Our findings highlight the complexity and polygenic nature of the pig gut microbial ecosystem. Prominent within the network were 5 regulators, PRDM15, STAT1, ssc-mir-371, SOX9 and RUNX2 which gathered 942, 607, 588, 284 and 273 connections, respectively. PRDM15 modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency and regulates the production of Th1- and Th2-type immune response. The signal transducer STAT1 has long been associated with immune processes and was recently identified as a potential regulator of vaccine response to porcine reproductive and respiratory syndrome. The list of regulators was enriched for immune-related pathways, and the list of predicted targets includes candidate genes previously reported as associated with microbiota profile in pigs, mice and human, such as SLIT3, SLC39A8, NOS1, IL1R2, DAB1, TOX3, SPP1, THSD7B, ELF2, PIANP, A2ML1, and IFNAR1. Moreover, we show the existence of host-genetic variants jointly associated with the relative abundance of butyrate producer bacteria and host performance. Conclusions Taken together, our results identified regulators, candidate genes, and mechanisms linked with microbiome modulation by the host. They further highlight the value of the proposed analytical pipeline to exploit pleiotropy and the crosstalk between bacteria and protists as significant contributors to host-microbiome interactions and identify genetic markers and candidate genes that can be incorporated in breeding program to improve host-performance and microbial traits.

scholarly journals Neurons interact with the microbiome: an evolutionary-informed perspective

Neuroforum ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Christoph Giez ◽  
Alexander Klimovich ◽  
Thomas C. G. Bosch
Keyword(s):  
Nervous System ◽  
Neural Circuits ◽  
Current Knowledge ◽  
System Development ◽  
Nervous System Development ◽  
Comprehensive Understanding ◽  
Strategic Model ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
And Function

Abstract Animals have evolved within the framework of microbes and are constantly exposed to diverse microbiota. Microbes colonize most, if not all, animal epithelia and influence the activity of many organs, including the nervous system. Therefore, any consideration on nervous system development and function in the absence of the recognition of microbes will be incomplete. Here, we review the current knowledge on the nervous systems of Hydra and its role in the host–microbiome communication. We show that recent advances in molecular and imaging methods are allowing a comprehensive understanding of the capacity of such a seemingly simple nervous system in the context of the metaorganism. We propose that the development, function and evolution of neural circuits must be considered in the context of host–microbe interactions and present Hydra as a strategic model system with great basic and translational relevance for neuroscience.

scholarly journals A Microbial Perspective on the Grand Challenges in Comparative Animal Physiology

mSystems ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Kevin D. Kohl
Keyword(s):  
Microbial Communities ◽  
Vertical Integration ◽  
Temporal Integration ◽  
Data Sets ◽  
Grand Challenges ◽  
Animal Physiology ◽  
Physiological Processes ◽  
Microbe Interactions ◽  
Animal Hosts ◽  
Host Microbe Interactions

ABSTRACTInteractions with microbial communities can have profound influences on animal physiology, thereby impacting animal performance and fitness. Therefore, it is important to understand the diversity and nature of host-microbe interactions in various animal groups (invertebrates, fish, amphibians, reptiles, birds, and mammals). In this perspective, I discuss how the field of host-microbe interactions can be used to address topics that have been identified as grand challenges in comparative animal physiology: (i) horizontal integration of physiological processes across organisms, (ii) vertical integration of physiological processes across organizational levels within organisms, and (iii) temporal integration of physiological processes during evolutionary change. Addressing these challenges will require the use of a variety of animal models and the development of systems approaches that can integrate large, multiomic data sets from both microbial communities and animal hosts. Integrating host-microbe interactions into the established field of comparative physiology represents an exciting frontier for both fields.

scholarly journals Optimal integration between host physiology and functions of the gut microbiome

2020 ◽  
Vol 375 (1808) ◽  
pp. 20190594 ◽  
Author(s):  
Samantha S. Fontaine ◽  
Kevin D. Kohl
Keyword(s):  
Microbial Communities ◽  
Physiological Function ◽  
Biological Organization ◽  
Theme Issue ◽  
Microbe Interactions ◽  
Host Physiology ◽  
Host Microbe Interactions ◽  
Host Evolution ◽  
Physiological Systems

Host-associated microbial communities have profound impacts on animal physiological function, especially nutrition and metabolism. The hypothesis of ‘symmorphosis’, which posits that the physiological systems of animals are regulated precisely to meet, but not exceed, their imposed functional demands, has been used to understand the integration of physiological systems across levels of biological organization. Although this idea has been criticized, it is recognized as having important heuristic value, even as a null hypothesis, and may, therefore, be a useful tool in understanding how hosts evolve in response to the function of their microbiota. Here, through a hologenomic lens, we discuss how the idea of symmorphosis may be applied to host-microbe interactions. Specifically, we consider scenarios in which host physiology may have evolved to collaborate with the microbiota to perform important functions, and, on the other hand, situations in which services have been completely outsourced to the microbiota, resulting in relaxed selection on host pathways. Following this theoretical discussion, we finally suggest strategies by which these currently speculative ideas may be explicitly tested to further our understanding of host evolution in response to their associated microbial communities. This article is part of the theme issue ‘The role of the microbiome in host evolution’.

scholarly journals Evolution of strong reproductive isolation in plants: broad-scale patterns and lessons from a perennial model group

2020 ◽  
Vol 375 (1806) ◽  
pp. 20190544 ◽  
Author(s):  
Huiying Shang ◽  
Jaqueline Hess ◽  
Melinda Pickup ◽  
David L. Field ◽  
Pär K. Ingvarsson ◽  
...  
Keyword(s):  
Reproductive Isolation ◽  
Association Studies ◽  
Great Promise ◽  
Genome Wide Association Studies ◽  
Model Group ◽  
Recombination Rates ◽  
Genome Wide ◽  
Theoretical Predictions ◽  
Tree Topologies ◽  
Exemplary Model

Many recent studies have addressed the mechanisms operating during the early stages of speciation, but surprisingly few studies have tested theoretical predictions on the evolution of strong reproductive isolation (RI). To help address this gap, we first undertook a quantitative review of the hybrid zone literature for flowering plants in relation to reproductive barriers. Then, using Populus as an exemplary model group, we analysed genome-wide variation for phylogenetic tree topologies in both early- and late-stage speciation taxa to determine how these patterns may be related to the genomic architecture of RI. Our plant literature survey revealed variation in barrier complexity and an association between barrier number and introgressive gene flow. Focusing on Populus, our genome-wide analysis of tree topologies in speciating poplar taxa points to unusually complex genomic architectures of RI, consistent with earlier genome-wide association studies. These architectures appear to facilitate the ‘escape’ of introgressed genome segments from polygenic barriers even with strong RI, thus affecting their relationships with recombination rates. Placed within the context of the broader literature, our data illustrate how phylogenomic approaches hold great promise for addressing the evolution and temporary breakdown of RI during late stages of speciation. This article is part of the theme issue ‘Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers'.

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