Advancing Our Functional Understanding of Host–Microbiota Interactions: A Need for New Types of Studies

Multicellular life evolved in the presence of microorganisms and formed complex associations with their microbiota, the sum of all associated archaea, bacteria, fungi, and viruses. These associations greatly affect the health and life history of the host, which led to a new understanding of “self” and establishment of the “metaorganism” concept.1 The Collaborative Research Centre (CRC) 1182 aims at elucidating the evolution and function of metaorganisms. Its annual conference, the Young Investigator Research Day (YIRD), serves as a platform for scientists of various disciplines to share novel findings on host–microbiota interactions, thereby providing a comprehensive overview of recent developments and new directions in metaorganism research. Even though we have gained tremendous insights into the composition and dynamics of host‐associated microbial communities and their correlations with host health and disease, it also became evident that moving from correlative toward functional studies is needed to examine the underlying mechanisms of interactions within the metaorganism. Non‐classical model organisms in particular possess significant potential to functionally address many open questions in metaorganism research. Here, we suggest and introduce a roadmap moving from correlation toward a functional understanding of host–microbiota interactions and highlight its potential in emerging ecological, agricultural, and translational medical applications

Functions of the Microbiota for the Physiology of Animal Metaorganisms

Animals are usually regarded as independent entities within their respective environments. However, within an organism, eukaryotes and prokaryotes interact dynamically to form the so-called metaorganism or holobiont, where each partner fulfils its versatile and crucial role. This review focuses on the interplay between microorganisms and multicellular eukaryotes in the context of host physiology, in particular aging and mucus-associated crosstalk. In addition to the interactions between bacteria and the host, we highlight the importance of viruses and nonmodel organisms. Moreover, we discuss current culturing and computational methodologies that allow a deeper understanding of underlying mechanisms controlling the physiology of metaorganisms

Tripartite symbiosis in Hydra viridissima: Understanding the interactions between host, algae and bacteria

The aim of the project was to understand the symbiotic interactions in Hydra viridissima metaorganism. The bipartite interaction between the host and the algae has been a subject of interest for decades, but the influence of bacteria on these interactions has always been overlooked. The first part of the thesis focused on expanding the understanding of the metabolic co-dependence between the host and the algae. Presented in chapter1, I showed the specificity of the metabolic genes in the host that aided in producing glutamine for the algae. Moreover, I could show that maltose, the photosynthetic sugar supplemented by the algae, was likely to be broken down into glucose before being utilized by the host. In the second part of this thesis, I expanded the view on symbiotic interactions in Hydra viridissima by taking the bacterial colonizers into consideration. Chapter 2.1 focuses on understanding the effect of algal symbionts on the bacterial composition. I could demonstrate that co-cultivation of symbiotic (hosts with algae) and aposymbiotic (hosts without algae) animals resulted in the transfer of an invasive bacterium Legionella sp. to the symbiotic animals. This bacterium was fitness costly for the host; it reduced the growth rate of the host and increased algal expulsion. These expelled algae were further taken up by the aposymbiotic animals. However, under the influence of algal photosynthesis, this bacterium was eventually lost from the population, thus portraying the role of algae in controlling the invasive species and maintaining the core microbiome of the host. Chapter 2.2 focuses on the effect of bacterial symbionts on the host and algal fitness. I assessed a wide array of fitness parameters and compared the germ-free (bacteria-free) symbiotic and aposymbiotic animals with the respective controls to study if there is any fitness loss in the absence of bacteria. Since the results were not conclusive and I could not observe any detectable effect of the bacteria, I replaced the native bacteria with complete sets of bacterial consortia from other Hydra species and assessed for their impact on host fitness. Interestingly, I could see reduced fitness in all animals that received foreign bacteria, thus portraying the importance of harboring the native, stable microbiota.Das Ziel dieses Projektes war es, die symbiotischen Mechanismen im Metaorganismus Hydra viridissima zu verstehen. Während die Interaktionen zwischen dem Wirt und den Algen schon seit Jahrzehnten untersuchtwird, wurde der Einfluss der Bakterien dabei bisher vernachlässigt. Im ersten Teil dieser Arbeit habe ich mich auf die Untersuchung der gegenseitigen Abhängigkeit von Wirt und Algen fokussiert. Im ersten Kapitel konnte ich zeigen, wie die Spezifität der metabolischen Komponenten im Wirt dazu beitrug, Glutamin für die Algen zu produzieren. Weiterhin konnte ich zeigen, dass der photosynthetisch hergestellte Zucker der Algen, Maltose, wahrscheinlich in Glukose gespalten wird, bevor er vom Wirt weiter metabolisiert wird. Im zweiten Teil dieser Arbeit habe ich den Blick auf die symbiotischen Interaktionen bei Hydra viridissima erweitert, indem ich die assoziierten Bakterien mit einbezog. Kapitel 2.1 behandelt den Effekt der symbiotischen Algen auf die Zusammensetzung des Mikrobioms. Ich konnte zeigen, dass die Kokultivierung von symbiotisch und aposymbiotischen Tieren zur Übertragung des invasiven Bakteriums Legionella sp. auf die symbiotischen Tiere führte. Dieses Bakterium reduzierte die Fitness des Wirts, indem es dessen Wachstumsrate verringerte und den Ausstoß von Algen erhöhte, welche dann von aposymbiotischen Tieren aufgenommen wurden. Allerdings verschwand dieses Bakterium unter dem Einfluss der Algenphotosynthese schließlich aus der Population. Dies verdeutlichte die Kontrolledurch die Algen auf die Invasionbakterieller Spezies und ihre Rolle in der Aufrechterhaltung des Kernmikrobiomsdes Wirts. Kapitel 2.2 konzentriert sich auf den Effekt der bakteriellen Symbionten auf die Fitness des Wirts und der Algen. Ich untersuchte eine Großzahl von Fitnessparametern zwischen keimfreien (bakterienfreien) symbiotischen und aposymbiotischen Tieren und den entsprechenden Kontrollen, um zu erfassen, ob es eine reduzierte Fitness in Abwesenheit der Bakterien gibt. Da die Ergebnisse nicht eindeutig waren und kein Effekt der Bakterien erkennbar war, ersetzte ich die natürlichen Bakterien mit bakteriellen Konsortien andererHydra Arten und untersuchte deren Einfluss auf die Wirt-Fitness. Interessanterweise konnte ich eine reduzierte Fitness in all diesen Tieren nachweisen, was die Wichtigkeit der arteigenen, stabilen Mikrobiota unterstreicht

Symbiotic Algae of Hydra viridissima Play a Key Role in Maintaining Homeostatic Bacterial Colonization

The freshwater polyp Hydra viridissima (H. viridissima) harbors endosymbiotic Chlorella algae in addition to a species-specific microbiome. The molecular basis of the symbiosis between Hydra and Chlorella has been characterized to be metabolic in nature. Here, we studied the interaction between the extracellularly located microbiota and the algal photobiont, which resides in Hydra's endodermal epithelium, with main focus on Legionella bacterium. We aimed at evaluating the influence of the symbiotic algae on microbial colonization and in shaping the host microbiome. We report that the microbiome composition of symbiotic and aposymbiotic (algae free) H. viridissima is significantly different and dominated by Legionella spp. Hvir in aposymbiotic animals. Co-cultivation of these animals resulted in horizontal transmission of Legionella spp. Hvir bacteria from aposymbiotic to symbiotic animals. Acquisition of this bacterium increased the release of algae into ambient water. From there, algae could subsequently be taken up again by the aposymbiotic animals. The presence of algal symbionts had negative impact on Legionella spp. Hvir and resulted in a decrease of the relative abundance of this bacterium. Prolonged co-cultivation ultimately resulted in the disappearance of the Legionella spp. Hvir bacterium from the Hydra tissue. Our observations suggest an important role of the photobiont in controlling an invasive species in a metacommunity and, thereby, shaping the microbiome