TY - JOUR A1 - Coelho, Luis Pedro A1 - Kultima, Jens Roat A1 - Costea, Paul Igor A1 - Fournier, Coralie A1 - Pan, Yuanlong A1 - Czarnecki-Maulden, Gail A1 - Hayward, Matthew Robert A1 - Forslund, Sofia K. A1 - Schmidt, Thomas Sebastian Benedikt A1 - Descombes, Patrick A1 - Jackson, Janet R. A1 - Li, Qinghong A1 - Bork, Peer T1 - Similarity of the dog and human gut microbiomes in gene content and response to diet JF - Microbiome N2 - Background Gut microbes influence their hosts in many ways, in particular by modulating the impact of diet. These effects have been studied most extensively in humans and mice. In this work, we used whole genome metagenomics to investigate the relationship between the gut metagenomes of dogs, humans, mice, and pigs. Results We present a dog gut microbiome gene catalog containing 1,247,405 genes (based on 129 metagenomes and a total of 1.9 terabasepairs of sequencing data). Based on this catalog and taxonomic abundance profiling, we show that the dog microbiome is closer to the human microbiome than the microbiome of either pigs or mice. To investigate this similarity in terms of response to dietary changes, we report on a randomized intervention with two diets (high-protein/low-carbohydrate vs. lower protein/higher carbohydrate). We show that diet has a large and reproducible effect on the dog microbiome, independent of breed or sex. Moreover, the responses were in agreement with those observed in previous human studies. Conclusions We conclude that findings in dogs may be predictive of human microbiome results. In particular, a novel finding is that overweight or obese dogs experience larger compositional shifts than lean dogs in response to a high-protein diet. KW - microbiome KW - diet KW - metagenomics KW - dog microbiome KW - human microbiome KW - mouse microbiome KW - pig microbiome Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223177 VL - 6 ER - TY - THES A1 - Ferretti, Pamela T1 - \(Clostridioides\) \(difficile\) beyond the disease-centred perspective: Beneficial properties in healthy infants and over-diagnosis in diseased adults identified by species- and SNV-based metagenomic analysis T1 - \(Clostridioides\) \(difficile\) jenseits der krankheitszentrierten Perspektive: Vorteilhafte Eigenschaften bei gesunden Säuglingen und Überdiagnose bei erkrankten Erwachsenen, identifiziert durch spezies- und SNV-basierte metagenomische Analyse N2 - Clostridioides difficile is a bacterial species well known for its ability to cause C. difficile infection (also known as CDI). The investigation of the role of this species in the human gut has been so far dominated by a disease-centred perspective, focused on studying C. difficile in relation to its associated disease. In this context, the first aim of this thesis was to combine publicly available metagenomic data to analyse the microbial composition of stool samples from patients diagnosed with CDI, with a particular focus on identifying a CDI-specific microbial signature. However, similarly to many other bacterial species inhabiting the human gut, C. difficile association with disease is not valid in absolute terms, as C. difficile can be found also among healthy subjects. Further aims of this thesis were to 1) identify potential C. difficile reservoirs by screening a wide range of habitats, hosts, body sites and age groups, and characterize the biotic context associated with C. difficile presence, and 2) investigate C. difficile within-species diversity and its toxigenic potential across different age groups. The first part of the thesis starts with the description of the concepts and definitions used to identify bacterial species and within-species diversity, and then proceeds to provide an overview of the bacterial species at the centre of my investigation, C. difficile. The first Chapter includes a detailed description of the discovery, biology and physiology of this clinically relevant species, followed by an overview of the diagnostic protocols used in the clinical setting to diagnose CDI. The second part of the thesis describes the methodology used to investigate the questions mentioned above, while the third part presents the results of such investigative effort. I first show that C. difficile could be found in only a fraction of the CDI samples and that simultaneous colonization of multiple enteropathogenic species able to cause CDI-like clinical manifestations is more common than previously thought, raising concerns about CDI overdiagnosis. I then show that the CDIassociated gut microbiome is characterized by a specific microbial signature, distinguishable from the community composition associated with non-CDI diarrhea. Beyond the nosocomial and CDI context, I show that while rarely found in adults, C. difficile is a common member of the infant gut microbiome, where its presence is associated with multiple indicators typical of a desirable healthy microbiome development. In addition, I describe C. difficile extensive carriage among asymptomatic subjects, of all age groups and a potentially novel clade of C. difficile identified exclusively among infants. Finally, I discuss the limitations, challenges and future perspectives of my investigation. N2 - Clostridioides difficile ist eine Bakterienart, die für ihre Fähigkeit bekannt ist, eine C. difficile-Infektion (auch bekannt als CDI) zu verursachen. Die Untersuchung der Rolle dieser Spezies im menschlichen Darm wurde bisher von einer krankheitszentrierten Perspektive dominiert, die sich auf die Untersuchung von C. difficile in Bezug auf die damit verbundene Erkrankung konzentrierte. In diesem Zusammenhang war das erste Ziel dieser Arbeit, öffentlich verfügbare metagenomische Daten zu kombinieren, um die mikrobielle Zusammensetzung von Stuhlproben von Patienten mit diagnostizierter CDI zu analysieren, mit besonderem Fokus auf der Identifizierung einer CDI-spezifischen mikrobiellen Signatur. Wie bei vielen anderen Bakterienarten, die den menschlichen Darm bewohnen, ist jedoch die Assoziation von C. difficile mit einer Krankheit nicht absolut gültig, da C. difficile auch bei gesunden Probanden gefunden werden kann. Weitere Ziele dieser Arbeit waren 1) die Identifizierung potenzieller C. difficile-Reservoirs durch das Screening einer Vielzahl von Habitaten, Wirten, Körperstellen und Altersgruppen und die Charakterisierung des mit der Präsenz von C. difficile verbundenen biotischen Kontexts und 2) Untersuchung von C. difficile innerhalb der Artenvielfalt und ihr toxigenes Potenzial über verschiedene Altersgruppen hinweg. Der erste Teil der Dissertation beginnt mit der Beschreibung der Konzepte und Definitionen, die verwendet werden, um Bakterienarten und innerhalb der Artenvielfalt zu identifizieren, und fährt dann fort, einen Überblick über die Bakterienarten zu geben, die im Zentrum meiner Untersuchung, C. difficile, stehen. Das erste Kapitel enthält eine detaillierte Beschreibung der Entdeckung, Biologie und Physiologie dieser klinisch relevanten Spezies, gefolgt von einem Überblick über die diagnostischen Protokolle, die im klinischen Umfeld zur Diagnose von CDI verwendet werden. Der zweite Teil der Arbeit beschreibt die Methodik zur Untersuchung der oben genannten Fragen, während der dritte Teil die Ergebnisse dieser Untersuchungsarbeit präsentiert. Ich zeige zunächst, dass C. difficile nur in einem Bruchteil der CDI-Proben gefunden werden konnte und dass die gleichzeitige Besiedlung mehrerer enteropathogener Spezies, die CDI-ähnliche klinische Manifestationen verursachen können, häufiger vorkommt als bisher angenommen, was Bedenken hinsichtlich einer CDI-Überdiagnose aufkommen lässt. Ich zeige dann, dass das CDI-assoziierte Darmmikrobiom durch eine spezifische mikrobielle Signatur gekennzeichnet ist, die sich von der Gemeinschaftszusammensetzung unterscheidet, die mit Nicht-CDI- Diarrhoe verbunden ist. Über den nosokomialen und CDI-Kontext hinaus zeige ich, dass C. difficile, obwohl es bei Erwachsenen selten vorkommt, ein häufiges Mitglied des Darmmikrobioms von Säuglingen ist, wo seine Anwesenheit mit mehreren Indikatoren verbunden ist, die typisch für eine wünschenswerte gesunde Mikrobiomentwicklung sind. Darüber hinaus beschreibe ich die ausgedehnte Beförderung von C. difficile bei asymptomatischen Patienten aller Altersgruppen und eine potenziell neue Gruppe von C. difficile, die ausschließlich bei Säuglingen identifiziert wurde. Abschließend diskutiere ich die Grenzen, Herausforderungen und Zukunftsperspektiven meiner Untersuchung. KW - microbiome KW - infant KW - C. difficile KW - CDI Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254170 ER - TY - JOUR A1 - Hickl, Oskar A1 - Heintz-Buschart, Anna A1 - Trautwein-Schult, Anke A1 - Hercog, Rajna A1 - Bork, Peer A1 - Wilmes, Paul A1 - Becher, Dörte T1 - Sample preservation and storage significantly impact taxonomic and functional profiles in metaproteomics studies of the human gut microbiome JF - Microorganisms N2 - With the technological advances of the last decade, it is now feasible to analyze microbiome samples, such as human stool specimens, using multi-omic techniques. Given the inherent sample complexity, there exists a need for sample methods which preserve as much information as possible about the biological system at the time of sampling. Here, we analyzed human stool samples preserved and stored using different methods, applying metagenomics as well as metaproteomics. Our results demonstrate that sample preservation and storage have a significant effect on the taxonomic composition of identified proteins. The overall identification rates, as well as the proportion of proteins from Actinobacteria were much higher when samples were flash frozen. Preservation in RNAlater overall led to fewer protein identifications and a considerable increase in the share of Bacteroidetes, as well as Proteobacteria. Additionally, a decrease in the share of metabolism-related proteins and an increase of the relative amount of proteins involved in the processing of genetic information was observed for RNAlater-stored samples. This suggests that great care should be taken in choosing methods for the preservation and storage of microbiome samples, as well as in comparing the results of analyses using different sampling and storage methods. Flash freezing and subsequent storage at −80 °C should be chosen wherever possible. KW - proteomics KW - metaproteomics KW - metagenomics KW - microbiome KW - microbiota KW - flash freezing KW - RNAlater KW - sample storage Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195976 SN - 2076-2607 VL - 7 IS - 9 ER - TY - JOUR A1 - Schmidt, Thomas S. B. A1 - Hayward, Matthew R. A1 - Coelho, Luiis P. A1 - Li, Simone S. A1 - Costea, Paul I. A1 - Voigt, Anita Y. A1 - Wirbel, Jakob A1 - Maistrenko, Oleksandr M. A1 - Alves, Renato J. C. A1 - Bergsten, Emma A1 - de Beaufort, Carine A1 - Sobhani, Iradj A1 - Heintz-Buschart, Anna A1 - Sunagawa, Shinichi A1 - Zeller, Georg A1 - Wilmes, Paul A1 - Bork, Peer T1 - Extensive transmission of microbes along the gastrointestinal tract JF - eLife N2 - The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease. KW - Colonization KW - Annotation KW - Dynamics KW - Accurate KW - Strains KW - Barrier KW - Health KW - Acids KW - Research Article KW - Computational and Systems Biology KW - Microbiology and Infectious Disease KW - microbiome KW - gastrointestinal tract KW - colorectal cancer KW - rheumatoid arthritis KW - metagenomics Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228954 VL - 8 ER - TY - JOUR A1 - Lehenberger, Maximilian A1 - Foh, Nina A1 - Göttlein, Axel A1 - Six, Diana A1 - Biedermann, Peter H. W. T1 - Nutrient-Poor Breeding Substrates of Ambrosia Beetles Are Enriched With Biologically Important Elements JF - Frontiers in Microbiology N2 - Fungus-farming within galleries in the xylem of trees has evolved independently in at least twelve lineages of weevils (Curculionidae: Scolytinae, Platypodinae) and one lineage of ship-timber beetles (Lymexylidae). Jointly these are termed ambrosia beetles because they actively cultivate nutritional “ambrosia fungi” as their main source of food. The beetles are obligately dependent on their ambrosia fungi as they provide them a broad range of essential nutrients ensuring their survival in an extremely nutrient-poor environment. While xylem is rich in carbon (C) and hydrogen (H), various elements essential for fungal and beetle growth, such as nitrogen (N), phosphorus (P), sulfur (S), potassium (K), calcium (Ca), magnesium (Mg), and manganese (Mn) are extremely low in concentration. Currently it remains untested how both ambrosia beetles and their fungi meet their nutritional requirements in this habitat. Here, we aimed to determine for the first time if galleries of ambrosia beetles are generally enriched with elements that are rare in uncolonized xylem tissue and whether these nutrients are translocated to the galleries from the xylem by the fungal associates. To do so, we examined natural galleries of three ambrosia beetle species from three independently evolved farming lineages, Xyleborinus saxesenii (Scolytinae: Xyleborini), Trypodendron lineatum (Scolytinae: Xyloterini) and Elateroides dermestoides (Lymexylidae), that cultivate unrelated ambrosia fungi in the ascomycete orders Ophiostomatales, Microascales, and Saccharomycetales, respectively. Several elements, in particular Ca, N, P, K, Mg, Mn, and S, were present in high concentrations within the beetles’ galleries but available in only very low concentrations in the surrounding xylem. The concentration of elements was generally highest with X. saxesenii, followed by T. lineatum and E. dermestoides, which positively correlates with the degree of sociality and productivity of brood per gallery. We propose that the ambrosia fungal mutualists are translocating essential elements through their hyphae from the xylem to fruiting structures they form on gallery walls. Moreover, the extremely strong enrichment observed suggests recycling of these elements from the feces of the insects, where bacteria and yeasts might play a role. KW - ambrosia beetle KW - ecological stoichiometry KW - microbiome KW - nutrients KW - macro- and micro-elements KW - element translocation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-237602 SN - 1664-302X VL - 12 ER - TY - JOUR A1 - Voulgari-Kokota, Anna A1 - Steffan-Dewenter, Ingolf A1 - Keller, Alexander T1 - Susceptibility of Red Mason Bee Larvae to Bacterial Threats Due to Microbiome Exchange with Imported Pollen Provisions JF - Insects N2 - Solitary bees are subject to a variety of pressures that cause severe population declines. Currently, habitat loss, temperature shifts, agrochemical exposure, and new parasites are identified as major threats. However, knowledge about detrimental bacteria is scarce, although they may disturb natural microbiomes, disturb nest environments, or harm the larvae directly. To address this gap, we investigated 12 Osmia bicornis nests with deceased larvae and 31 nests with healthy larvae from the same localities in a 16S ribosomal RNA (rRNA) gene metabarcoding study. We sampled larvae, pollen provisions, and nest material and then contrasted bacterial community composition and diversity in healthy and deceased nests. Microbiomes of pollen provisions and larvae showed similarities for healthy larvae, whilst this was not the case for deceased individuals. We identified three bacterial taxa assigned to Paenibacillus sp. (closely related to P. pabuli/amylolyticus/xylanexedens), Sporosarcina sp., and Bacillus sp. as indicative for bacterial communities of deceased larvae, as well as Lactobacillus for corresponding pollen provisions. Furthermore, we performed a provisioning experiment, where we fed larvae with untreated and sterilized pollens, as well as sterilized pollens inoculated with a Bacillus sp. isolate from a deceased larva. Untreated larval microbiomes were consistent with that of the pollen provided. Sterilized pollen alone did not lead to acute mortality, while no microbiome was recoverable from the larvae. In the inoculation treatment, we observed that larval microbiomes were dominated by the seeded bacterium, which resulted in enhanced mortality. These results support that larval microbiomes are strongly determined by the pollen provisions. Further, they underline the need for further investigation of the impact of detrimental bacterial acquired via pollens and potential buffering by a diverse pollen provision microbiome in solitary bees. KW - Osmia bicornis KW - solitary bee KW - bacterial transmission KW - microbiome KW - pollen provisions KW - pathogen KW - secondary invader KW - Paenibacillus KW - Bacillus KW - Sporosarcina Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207948 SN - 2075-4450 VL - 11 IS - 6 ER - TY - JOUR A1 - Scherzad, Agmal A1 - Hagen, Rudolf A1 - Hackenberg, Stephan T1 - Current Understanding of Nasal Epithelial Cell Mis-Differentiation JF - Journal of Inflammation Research N2 - The functional role of the respiratory epithelium is to generate a physical barrier. In addition, the epithelium supports the innate and acquired immune system through various cytokines and chemokines. However, epithelial cells are also involved in the pathogenesis of various respiratory diseases, some of which are mediated by increased permeability of the mucosal membrane or disturbed mucociliary transport. In addition, it has been shown that epithelial cells are involved in the development of inflammatory respiratory diseases. The following review article focuses on the aspects of epithelial mis-differentiation, in particular with respect to nasal mucosal barrier function, epithelial immunogenicity, nasal epithelial-mesenchymal transition and nasal microbiome. KW - nasal mucosal barrier function KW - tight junction KW - epithelial-mesenchymal transition KW - microbiome Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228562 VL - 12 ER - TY - JOUR A1 - Humberg, Alexander A1 - Fortmann, Ingmar A1 - Siller, Bastian A1 - Kopp, Matthias Volkmar A1 - Herting, Egbert A1 - Göpel, Wolfgang A1 - Härtel, Christoph T1 - Preterm birth and sustained inflammation: consequences for the neonate JF - Seminars in Immunopathology N2 - Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis (“first inflammatory hit”). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia (“second inflammatory hit”). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important “third-trimester” adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome. KW - preterm infants KW - sustained inflammation KW - sepsis KW - microbiome KW - neurocognitive outcome KW - chronic pulmonary insufficiency of prematurity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235019 SN - 1863-2297 VL - 42 ER - TY - JOUR A1 - Costea, Paul I. A1 - Coelho, Louis Pedro A1 - Sunagawa, Shinichi A1 - Munch, Robin A1 - Huerta-Cepas, Jaime A1 - Forslund, Kristoffer A1 - Hildebrand, Falk A1 - Kushugulova, Almagul A1 - Zeller, Georg A1 - Bork, Peer T1 - Subspecies in the global human gut microbiome JF - Molecular Systems Biology N2 - Population genomics of prokaryotes has been studied in depth in only a small number of primarily pathogenic bacteria, as genome sequences of isolates of diverse origin are lacking for most species. Here, we conducted a large‐scale survey of population structure in prevalent human gut microbial species, sampled from their natural environment, with a culture‐independent metagenomic approach. We examined the variation landscape of 71 species in 2,144 human fecal metagenomes and found that in 44 of these, accounting for 72% of the total assigned microbial abundance, single‐nucleotide variation clearly indicates the existence of sub‐populations (here termed subspecies). A single subspecies (per species) usually dominates within each host, as expected from ecological theory. At the global scale, geographic distributions of subspecies differ between phyla, with Firmicutes subspecies being significantly more geographically restricted. To investigate the functional significance of the delineated subspecies, we identified genes that consistently distinguish them in a manner that is independent of reference genomes. We further associated these subspecies‐specific genes with properties of the microbial community and the host. For example, two of the three Eubacterium rectale subspecies consistently harbor an accessory pro‐inflammatory flagellum operon that is associated with lower gut community diversity, higher host BMI, and higher blood fasting insulin levels. Using an additional 676 human oral samples, we further demonstrate the existence of niche specialized subspecies in the different parts of the oral cavity. Taken together, we provide evidence for subspecies in the majority of abundant gut prokaryotes, leading to a better functional and ecological understanding of the human gut microbiome in conjunction with its host. KW - biology KW - genetic variation KW - metagenomics KW - microbiome KW - population structure KW - prokaryotic subspecies Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172674 VL - 13 IS - 12 ER - TY - JOUR A1 - Vogel, Jörg T1 - An RNA biology perspective on species‐specific programmable RNA antibiotics JF - Molecular Microbiology N2 - Our body is colonized by a vast array of bacteria the sum of which forms our microbiota. The gut alone harbors >1,000 bacterial species. An understanding of their individual or synergistic contributions to human health and disease demands means to interfere with their functions on the species level. Most of the currently available antibiotics are broad‐spectrum, thus too unspecific for a selective depletion of a single species of interest from the microbiota. Programmable RNA antibiotics in the form of short antisense oligonucleotides (ASOs) promise to achieve precision manipulation of bacterial communities. These ASOs are coupled to small peptides that carry them inside the bacteria to silence mRNAs of essential genes, for example, to target antibiotic‐resistant pathogens as an alternative to standard antibiotics. There is already proof‐of‐principle with diverse bacteria, but many open questions remain with respect to true species specificity, potential off‐targeting, choice of peptides for delivery, bacterial resistance mechanisms and the host response. While there is unlikely a one‐fits‐all solution for all microbiome species, I will discuss how recent progress in bacterial RNA biology may help to accelerate the development of programmable RNA antibiotics for microbiome editing and other applications. KW - antibiotic KW - microbiome KW - RNA-seq KW - small RNA Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214869 VL - 113 IS - 3 SP - 550 EP - 559 ER -