The potential importance of the built-environment microbiome and its impact on human health.

There is increasing evidence that interactions between microbes and their hosts not only play a role in determining health and disease but also in emotions, thought, and behavior. Built environments greatly influence microbiome exposures because of their built-in highly specific microbiomes coproduced with myriad metaorganisms including humans, pets, plants, rodents, and insects. Seemingly static built structures host complex ecologies of microorganisms that are only starting to be mapped. These microbial ecologies of built environments are directly and interdependently affected by social, spatial, and technological norms. Advances in technology have made these organisms visible and forced the scientific community and architects to rethink gene-environment and microbe interactions respectively. Thus, built environment design must consider the microbiome, and research involving host-microbiome interaction must consider the built-environment. This paradigm shift becomes increasingly important as evidence grows that contemporary built environments are steadily reducing the microbial diversity essential for human health, well-being, and resilience while accelerating the symptoms of human chronic diseases including environmental allergies, and other more life-altering diseases. New models of design are required to balance maximizing exposure to microbial diversity while minimizing exposure to human-associated diseases. Sustained trans-disciplinary research across time (evolutionary, historical, and generational) and space (cultural and geographical) is needed to develop experimental design protocols that address multigenerational multispecies health and health equity in built environments.

Symbiosis: the other cells in development.

Animal development is an inherently complex process that is regulated by highly conserved genomic networks, and the resulting phenotype may remain plastic in response to environmental signals. Despite development having been studied in a more natural setting for the past few decades, this framework often precludes the role of microbial prokaryotes in these processes. Here, we address how microbial symbioses impact animal development from the onset of gametogenesis through adulthood. We then provide a first assessment of which developmental processes may or may not be influenced by microbial symbioses and, in doing so, provide a holistic view of the budding discipline of developmental symbiosis.

Hydra and the hair follicle - An unconventional comparative biology approach to exploring the human holobiont.

The microbiome of human hair follicles (HFs) has emerged as an important player in different HF and skin pathologies, yet awaits in-depth exploration. This raises questions regarding the tightly linked interactions between host environment, nutrient dependency of host-associated microbes, microbial metabolism, microbe-microbe interactions and host immunity. The use of simple model systems facilitates addressing generally important questions and testing overarching, therapeutically relevant principles that likely transcend obvious interspecies differences. Here, we evaluate the potential of the freshwater polyp Hydra, to dissect fundamental principles of microbiome regulation by the host, that is the human HF. In particular, we focus on therapeutically targetable host-microbiome interactions, such as nutrient dependency, microbial interactions and host defence. Offering a new lens into the study of HF - microbiota interactions, we argue that general principles of how Hydra manages its microbiota can inform the development of novel, microbiome-targeting therapeutic interventions in human skin disease.

The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome.

The COVID-19 pandemic has the potential to affect the human microbiome in infected and uninfected individuals, having a substantial impact on human health over the long term. This pandemic intersects with a decades-long decline in microbial diversity and ancestral microbes due to hygiene, antibiotics, and urban living (the hygiene hypothesis). High-risk groups succumbing to COVID-19 include those with preexisting conditions, such as diabetes and obesity, which are also associated with microbiome abnormalities. Current pandemic control measures and practices will have broad, uneven, and potentially long-term effects for the human microbiome across the planet, given the implementation of physical separation, extensive hygiene, travel barriers, and other measures that influence overall microbial loss and inability for reinoculation. Although much remains uncertain or unknown about the virus and its consequences, implementing pandemic control practices could significantly affect the microbiome. In this Perspective, we explore many facets of COVID-19-induced societal changes and their possible effects on the microbiome, and discuss current and future challenges regarding the interplay between this pandemic and the microbiome. Recent recognition of the microbiome's influence on human health makes it critical to consider both how the microbiome, shaped by biosocial processes, affects susceptibility to the coronavirus and, conversely, how COVID-19 disease and prevention measures may affect the microbiome. This knowledge may prove key in prevention and treatment, and long-term biological and social outcomes of this pandemic.

The Role of DNA Methylation in Genome Defense in Cnidaria and Other Invertebrates.

Considerable attention has recently been focused on the potential involvement of DNA methylation in regulating gene expression in cnidarians. Much of this work has been centered on corals, in the context of changes in methylation perhaps facilitating adaptation to higher seawater temperatures and other stressful conditions. Although first proposed more than 30 years ago, the possibility that DNA methylation systems function in protecting animal genomes against the harmful effects of transposon activity has largely been ignored since that time. Here, we show that transposons are specifically targeted by the DNA methylation system in cnidarians, and that the youngest transposons (i.e., those most likely to be active) are most highly methylated. Transposons in longer and highly active genes were preferentially methylated and, as transposons aged, methylation levels declined, reducing the potentially harmful side effects of CpG methylation. In Cnidaria and a range of other invertebrates, correlation between the overall extent of methylation and transposon content was strongly supported. Present transposon burden is the dominant factor in determining overall level of genomic methylation in a range of animals that diverged in or before the early Cambrian, suggesting that genome defense represents the ancestral role of CpG methylation.

Bacteria- and temperature-regulated peptides modulate ß-catenin signaling in Hydra.

Animal development has traditionally been viewed as an autonomous process directed by the host genome. But, in many animals, biotic and abiotic cues, like temperature and bacterial colonizers, provide signals for multiple developmental steps. Hydra offers unique features to encode these complex interactions of developmental processes with biotic and abiotic factors, and we used it here to investigate the impact of bacterial colonizers and temperature on the pattern formation process. In Hydra, formation of the head organizer involves the canonical Wnt pathway. Treatment with alsterpaullone (ALP) results in acquiring characteristics of the head organizer in the body column. Intriguingly, germfree Hydra polyps are significantly more sensitive to ALP compared to control polyps. In addition to microbes, ß-catenin-dependent pattern formation is also affected by temperature. Gene expression analyses led to the identification of two small secreted peptides, named Eco1 and Eco2, being up-regulated in the response to both Curvibacter sp., the main bacterial colonizer of Hydra, and low temperatures. Loss-of-function experiments revealed that Eco peptides are involved in the regulation of pattern formation and have an antagonistic function to Wnt signaling in Hydra.

Prototypical pacemaker neurons interact with the resident microbiota.

Pacemaker neurons exert control over neuronal circuit function by their intrinsic ability to generate rhythmic bursts of action potential. Recent work has identified rhythmic gut contractions in human, mice, and hydra to be dependent on both neurons and the resident microbiota. However, little is known about the evolutionary origin of these neurons and their interaction with microbes. In this study, we identified and functionally characterized prototypical ANO/SCN/TRPM ion channel-expressing pacemaker cells in the basal metazoan Hydra by using a combination of single-cell transcriptomics, immunochemistry, and functional experiments. Unexpectedly, these prototypical pacemaker neurons express a rich set of immune-related genes mediating their interaction with the microbial environment. Furthermore, functional experiments gave a strong support to a model of the evolutionary emergence of pacemaker cells as neurons using components of innate immunity to interact with the microbial environment and ion channels to generate rhythmic contractions.

Symbiont transmission in marine sponges: reproduction, development, and metamorphosis.

Marine sponges (phylum Porifera) form symbioses with diverse microbial communities that can be transmitted between generations through their developmental stages. Here, we integrate embryology and microbiology to review how symbiotic microorganisms are transmitted in this early-diverging lineage. We describe that vertical transmission is widespread but not universal, that microbes are vertically transmitted during a select developmental window, and that properties of the developmental microbiome depends on whether a species is a high or low microbial abundance sponge. Reproduction, development, and symbiosis are thus deeply rooted, but why these partnerships form remains the central and elusive tenet of these developmental symbioses.

Dynamic interactions within the host-associated microbiota cause tumor formation in the basal metazoan Hydra.

The extent to which disturbances in the resident microbiota can compromise an animal's health is poorly understood. Hydra is one of the evolutionary oldest animals with naturally occurring tumors. Here, we found a causal relationship between an environmental spirochete (Turneriella spec.) and tumorigenesis in Hydra. Unexpectedly, virulence of this pathogen requires the presence of Pseudomonas spec., a member of Hydra´s beneficial microbiome indicating that dynamic interactions between a resident bacterium and a pathogen cause tumor formation. The observation points to the crucial role of commensal bacteria in maintaining tissue homeostasis and adds support to the view that microbial community interactions are essential for disease. These findings in an organism that shares deep evolutionary connections with all animals have implications for our understanding of cancer.

Neutrality in the Metaorganism.

Almost all animals and plants are inhabited by diverse communities of microorganisms, the microbiota, thereby forming an integrated entity, the metaorganism. Natural selection should favor hosts that shape the community composition of these microbes to promote a beneficial host-microbe symbiosis. Indeed, animal hosts often pose selective environments, which only a subset of the environmentally available microbes are able to colonize. How these microbes assemble after colonization to form the complex microbiota is less clear. Neutral models are based on the assumption that the alternatives in microbiota community composition are selectively equivalent and thus entirely shaped by random population dynamics and dispersal. Here, we use the neutral model as a null hypothesis to assess microbiata composition in host organisms, which does not rely on invoking any adaptive processes underlying microbial community assembly. We show that the overall microbiota community structure from a wide range of host organisms, in particular including previously understudied invertebrates, is in many cases consistent with neutral expectations. Our approach allows to identify individual microbes that are deviating from the neutral expectation and are therefore interesting candidates for further study. Moreover, using simulated communities, we demonstrate that transient community states may play a role in the deviations from the neutral expectation. Our findings highlight that the consideration of neutral processes and temporal changes in community composition are critical for an in-depth understanding of microbiota-host interactions.

Boundary maintenance in the ancestral metazoan Hydra depends on histone acetylation.

Much of boundary formation during development remains to be understood, despite being a defining feature of many animal taxa. Axial patterning of Hydra, a member of the ancient phylum Cnidaria which diverged prior to the bilaterian radiation, involves a steady-state of production and loss of tissue, and is dependent on an organizer located in the upper part of the head. We show that the sharp boundary separating tissue in the body column from head and foot tissue depends on histone acetylation. Histone deacetylation disrupts the boundary by affecting numerous developmental genes including Wnt components and prevents stem cells from entering the position dependent differentiation program. Overall, our results suggest that reversible histone acetylation is an ancient regulatory mechanism for partitioning the body axis into domains with specific identity, which was present in the common ancestor of cnidarians and bilaterians, at least 600 million years ago.

Eco-Evo-Devo: developmental symbiosis and developmental plasticity as evolutionary agents.

The integration of research from developmental biology and ecology into evolutionary theory has given rise to a relatively new field, ecological evolutionary developmental biology (Eco-Evo-Devo). This field integrates and organizes concepts such as developmental symbiosis, developmental plasticity, genetic accommodation, extragenic inheritance and niche construction. This Review highlights the roles that developmental symbiosis and developmental plasticity have in evolution. Developmental symbiosis can generate particular organs, can produce selectable genetic variation for the entire animal, can provide mechanisms for reproductive isolation, and may have facilitated evolutionary transitions. Developmental plasticity is crucial for generating novel phenotypes, facilitating evolutionary transitions and altered ecosystem dynamics, and promoting adaptive variation through genetic accommodation and niche construction. In emphasizing such non-genomic mechanisms of selectable and heritable variation, Eco-Evo-Devo presents a new layer of evolutionary synthesis.

The Microbiome Mediates Environmental Effects on Aging.

Humans' indigenous microbes strongly influence organ functions in an age- and diet-dependent manner, adding an important dimension to aging biology that remains poorly understood. Although age-related differences in the gut microbiota composition correlate with age-related loss of organ function and diseases, including inflammation and frailty, variation exists among the elderly, especially centenarians and people living in areas of extreme longevity. Studies using short-lived as well as nonsenescent model organisms provide surprising functional insights into factors affecting aging and implicate attenuating effects of microbes as well as a crucial role for certain transcription factors like forkhead box O. The unexpected beneficial effects of microbes on aged animals imply an even more complex interplay between the gut microbiome and the host. The microbiome constitutes the major interface between humans and the environment, is influenced by biosocial stressors and behaviors, and mediates effects on health and aging processes, while being moderated by sex and developmental stages.

Evolutionary "Experiments" in Symbiosis: The Study of Model Animals Provides Insights into the Mechanisms Underlying the Diversity of Host-Microbe Interactions.

Current work in experimental biology revolves around a handful of animal species. Studying only a few organisms limits science to the answers that those organisms can provide. Nature has given us an overwhelming diversity of animals to study, and recent technological advances have greatly accelerated the ability to generate genetic and genomic tools to develop model organisms for research on host-microbe interactions. With the help of such models the authors therefore hope to construct a more complete picture of the mechanisms that underlie crucial interactions in a given metaorganism (entity consisting of a eukaryotic host with all its associated microbial partners). As reviewed here, new knowledge of the diversity of host-microbe interactions found across the animal kingdom will provide new insights into how animals develop, evolve, and succumb to the disease.

[The skin microbiome as a natural protection factor : Insights from basic research]. / Mikrobiom als natürlicher Schutzfaktor : Perspektiven aus der Grundlagenforschung.

BACKGROUND: A new generation of technologies is uncovering a large number of microorganisms that are closely associated with the skin. Any disturbance of the interaction between skin cells and colonizing microbes has deleterious consequences. The impoverishment of the diversity of microbiome has been progressing for decades as part of a modern, globalized lifestyle. In maintaining good health, the microbes living in and on the skin and other organs must also be taken into account in addition to genetic aspects. All epithelia, including the skin, are colonized with a large number of microbes. OBJECTIVE: The function of the microbiome in the skin and other organs is described. MATERIALS AND METHODS: Basic research papers are discussed. RESULTS: The microbiome of the skin is very important for maintaining healthy skin. CONCLUSIONS: We need to understand our body as a multiorganismic metaorganism in order to be able to react intelligently to the challenges of a continually changing environment.

Competing forces maintain the Hydra metaorganism.

Our conventional view of multicellular organisms often overlooks the fact that they are metaorganisms. They consist of a host, which is comprised of both a community of self-replicating cells that can compete as well as cooperate and a community of associated microorganisms. This newly discovered complexity raises a profound challenge: How to maintain such a multicellular association that includes independently replicating units and even different genotypes? Here, we identify competing forces acting at the host tissue level, the host-microbe interface, and within the microbial community as key factors to maintain the metaorganism Hydra. Maintenance of host tissue integrity, as well as proper regulation and management of the multiorganismic interactions are fundamental to organismal survival and health. Findings derived from the in vivo context of the Hydra model may provide one of the simplest possible systems to address questions on how a metaorganism is established and remains in balance over time.

Bdellovibrio and Like Organisms Are Predictors of Microbiome Diversity in Distinct Host Groups.

Biodiversity is generally believed to be a main determinant of ecosystem functioning. This principle also applies to the microbiome and could consequently contribute to host health. According to ecological theory, communities are shaped by top predators whose direct and indirect interactions with community members cause stability and diversity. Bdellovibrio and like organisms (BALOs) are a neglected group of predatory bacteria that feed on Gram-negative bacteria and can thereby influence microbiome composition. We asked whether BALOs can predict biodiversity levels in microbiomes from distinct host groups and environments. We demonstrate that genetic signatures of BALOs are commonly found within the 16S rRNA reads from diverse host taxa. In many cases, their presence, abundance, and especially richness are positively correlated with overall microbiome diversity. Our findings suggest that BALOs can act as drivers of microbial alpha-diversity and should therefore be considered candidates for the restoration of microbiomes and the prevention of dysbiosis.

Rethinking the Role of the Nervous System: Lessons From the Hydra Holobiont.

Here we evaluate our current understanding of the function of the nervous system in Hydra, a non-bilaterian animal which is among the first metazoans that contain neurons. We highlight growing evidence that the nervous system, with its rich repertoire of neuropeptides, is involved in controlling resident beneficial microbes. We also review observations that indicate that microbes affect the animal's behavior by directly interfering with neuronal receptors. These findings provide new insight into the original role of the nervous system, and suggest that it emerged to orchestrate multiple functions including host-microbiome interactions. The excitement of future research in the Hydra model now relies on uncovering the common rules and principles that govern the interaction between neurons and microbes and the extent to which such laws might apply to other and more complex organisms.

Host modification of a bacterial quorum-sensing signal induces a phenotypic switch in bacterial symbionts.

Bacterial communities colonize epithelial surfaces of most animals. Several factors, including the innate immune system, mucus composition, and diet, have been identified as determinants of host-associated bacterial communities. Here we show that the early branching metazoan Hydra is able to modify bacterial quorum-sensing signals. We identified a eukaryotic mechanism that enables Hydra to specifically modify long-chain 3-oxo-homoserine lactones into their 3-hydroxy-HSL counterparts. Expression data revealed that Hydra's main bacterial colonizer, Curvibacter sp., responds differentially to N-(3-hydroxydodecanoyl)-l-homoserine lactone (3OHC12-HSL) and N-(3-oxododecanoyl)-l-homoserine lactone (3OC12-HSL). Investigating the impacts of the different N-acyl-HSLs on host colonization elucidated that 3OHC12-HSL allows and 3OC12-HSL represses host colonization of Curvibacter sp. These results show that an animal manipulates bacterial quorum-sensing signals and that this modification leads to a phenotypic switch in the bacterial colonizers. This mechanism may enable the host to manipulate the gene expression and thereby the behavior of its bacterial colonizers.