The establishment of host-bacterial colonization during development is a fundamental process influencing the fitness of many organisms, but the factors controlling community membership and influencing the establishment of the microbial ecosystem during development are poorly understood. The starlet sea anemone Nematostella vectensis serves as a cnidarian model organism due to the availability of laboratory cultures and its high tolerance for broad ranges of salinity and temperature. Here, we show that the anemone's epithelia are colonized by diverse bacterial communities and that the composition of its microbiota is tightly coupled to host development. Environmental variations led to robust adjustments in the microbial composition while still maintaining the ontogenetic core signature. In addition, analysis of bacterial communities of Nematostella polyps from five different populations revealed a strong correlation between host biogeography and bacterial diversity despite years of laboratory culturing. These observed variations in fine-scale community composition following environmental change and for individuals from different geographic origins could represent the microbiome's contribution to host acclimation and potentially adaptation, respectively, and thereby contribute to the maintenance of homeostasis due to environmental changes.

Spontaneous contractile activity, such as gut peristalsis, is ubiquitous in animals and is driven by pacemaker cells. In humans, disruption of the contraction pattern leads to gastrointestinal conditions, which are also associated with gut microbiota dysbiosis. Spontaneous contractile activity is also present in animals lacking gastrointestinal tract. Here we show that spontaneous body contractions in Hydra are modulated by symbiotic bacteria. Germ-free animals display strongly reduced and less regular contraction frequencies. These effects are partially restored by reconstituting the natural microbiota. Moreover, soluble molecule(s) produced by symbiotic bacteria may be involved in contraction frequency modulation. As the absence of bacteria does not impair the contractile ability itself, a microbial effect on the pacemakers seems plausible. Our findings indicate that the influence of bacteria on spontaneous contractile activity is present in the early-branching cnidarian hydra as well as in Bilateria, and thus suggest an evolutionary ancient origin of interaction between bacteria and metazoans, opening a window into investigating the roots of human motility disorders.

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.

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 which 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. *

Microcin H47 (MccH47) is an antimicrobial peptide produced by some strains of Escherichia coli that has demonstrated inhibitory activity against enteric pathogens in vivo and has been heterologously overexpressed in proof-of-concept engineered probiotic applications. While most studies clearly demonstrate inhibitory activity against E. coli isolates, there are conflicting results on the qualitative capacity for MccH47 to inhibit strains of Salmonella. Here, we rectify these inconsistencies via the overexpression and purification of a form of MccH47, termed MccH47-monoglycosylated enterobactin (MccH47−MGE). We then use purified MccH47 to estimate minimum inhibitory concentrations (MICs) against a number of medically relevant Enterobacteriaceae, including Salmonella and numerous multidrug resistant (MDR) strains. While previous reports suggested that the spectrum of activity for MccH47 is quite narrow and restricted to activity against E. coli, our data demonstrate that MccH47 has broad and potent activity within the Enterobacteriaceae family, suggesting it as a candidate for further development toward treating MDR enteric infections.

How multicellular organisms assess and control their size is a fundamental question in biology, yet the molecular and genetic mechanisms that control organ or organism size remain largely unsolved. The freshwater polyp Hydra demonstrates a high capacity to adapt its body size to different temperatures. Here we identify the molecular mechanisms controlling this phenotypic plasticity and show that temperature-induced cell number changes are controlled by Wnt- and TGF-β signaling. Further we show that insulin-like peptide receptor (INSR) and forkhead box protein O (FoxO) are important genetic drivers of size determination controlling the same developmental regulators. Thus, environmental and genetic factors directly affect developmental mechanisms in which cell number is the strongest determinant of body size. These findings identify the basic mechanisms as to how size is regulated on an organismic level and how phenotypic plasticity is integrated into conserved developmental pathways in an evolutionary informative model organism.

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.

The aging process is considered to be the result of accumulating cellular deterioration in an individual organism over time. It can be affected by the combined influence of genetic, epigenetic, and environmental factors including life-style-associated events. In the non-senescent freshwater polyp Hydra, one of the classical model systems for evolutionary developmental biology and regeneration, transcription factor FoxO modulates both stem cell proliferation and innate immunity. This provides strong support for the role of FoxO as a critical rate-of-aging regulator. However, how environmental factors interact with FoxO remains unknown. Here, we find that deficiency in FoxO signaling in Hydra leads to dysregulation of antimicrobial peptide expression and that FoxO loss-of-function polyps are impaired in selection for bacteria resembling the native microbiome and more susceptible to colonization of foreign bacteria. These findings reveal a key role of FoxO signaling in the communication between host and microbiota and embed the evolutionary conserved longevity factor FoxO into the holobiont concept.