Biology subjects

Weber, B.

Publications and source records attributed to Weber, B..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Leptomeningeal collaterals regulate reperfusion in ischemic stroke

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet unknown functions. Utilizing a thrombin-based mouse model of stroke and the gold standard fibrinolytic treatment rt-PA, we here show that LMCs play a critical role in preserving vascular function in ischemic territories. We applied laser speckle contrast imaging, ultrafast ultrasound, and two-photon microscopy, to show that after thrombolysis, LMCs allow for gradual reperfusion resulting in small infarcts. On the contrary, in mice with poor LMCs, distal segments of recanalized arteries collapse and deleterious hyperemia causes hemorrhage and mortality. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for gradual reperfusion of ischemic tissues after stroke.

neuroscience↗

bioRxiv2023

Acoustic trapping and navigation of microrobots in the mouse brain vasculature

Many cerebrovascular and neurodegenerative diseases are currently challenging to treat due to the complex and delicate anatomy of the brain. The use of microrobots can create new opportunities in brain research due to their ability to access hard-to-reach regions and empower various biological applications; however, little is known about the functionality of microrobots in the brain, owing to their limited imaging modalities and intravascular challenges such as high blood flow velocities, osmotic pressures, and cellular responses. Here, we present an acoustic, non-invasive, biocompatible microrobot actuation system, for in vivo navigation in the bloodstream, in which microrobots are formed by lipid-shelled microbubbles that aggregate and propel under the force of acoustic irradiation. We investigated their capacities in vitro within a microfluidic 3D setup and in vivo in a living mouse brain. We show that microrobots can self-assemble and navigate upstream in the brain vasculature. Our microrobots achieved upstream velocities of up to 1.5 m/s and overcame blood flows of ~10 mm/s. Our results prove that microbubble-based microrobots are scalable to the complex 3D living milieu. Significance StatementNumerous brain diseases, including ischemic stroke, Alzheimers disease, and glioblastoma, may benefit from local and targeted therapies. Although they show great promise, microrobots have not yet demonstrated successful in vivo navigation inside the brain, as the challenging flow conditions and the complex 3D vascular network in the brain pose fundamental limitations. Here, we apply acoustically driven microrobots with the capacity for self-assembly and real-time navigation, including navigation against blood flow up to 10 mm/s, used for the first time inside the brain vasculature of a living mouse. The ultrasound manipulation of microrobots inside animal models provides a much-needed pathway for the advancement of preclinical research.

bioengineering↗

bioRxiv2022

Investigation of whether oxytocin and trust play a role in placebo effects of marketing actions

Expectations about the quality of a medical treatment influence how much an inert treatment helps to improve patient well-being. Similarly, expectations about the quality of products influence how identical goods and services are evaluated differently after their consumption. One driver for such "placebo effects" in medical treatments is social cognition in the form of trust, which may be influenced by the hormone oxytocin. An open question is whether trust and oxytocin play similar roles in marketing placebo effects. To answer this question, we combined oxytocin administration (24 IU) and trust questionnaires in a pre-registered double-blind randomized between-subjects study design (Nfood tasting task = 223; Ncognitive performance task = 202). We could not find evidence that oxytocin and trust play a role in placebo effects of marketing actions. Together with other recent null findings from oxytocin administration studies, these findings question the role trust might play in different types of placebo effects.

neuroscience↗

bioRxiv2022

Potassium regulates axon-oligodendrocyte signaling and metabolic coupling in white matter

The integrity of myelinated axons relies on homeostatic support from oligodendrocytes (OLs), which is essential for brain function. However, the mechanisms by which OLs detect axonal spiking and rapidly control axon-OL metabolic coupling are largely unknown. Here, we combine optic nerve electrophysiology and two-photon imaging to study activity-dependent calcium (Ca2+) dynamics in OLs and metabolite fluxes in myelinated axons. Both high-frequency axonal firing and extracellular potassium (K+) elevations trigger a fast Ca2+ response in OLs that is facilitated by barium-sensitive, inwardly rectifying K+ channels. Using OL-specific Kir4.1 knockout mice (Kir4.1 cKO) we now demonstrate that, in addition to being crucial for K+ clearance, oligodendroglial Kir4.1 regulates axonal energy metabolism and long-term axonal integrity. Before the manifestation of axonal damage, we observed reduced glucose transporter GLUT1 and monocarboxylate transporter MCT1 expression in myelin of young Kir4.1 cKO mice, suggesting early deficits in metabolite supply to axons. Strikingly, we found lower resting lactate levels and activity-induced lactate surges in optic nerve axons of young Kir4.1 cKO mice. Moreover, both axonal glucose uptake and consumption were hampered in the absence of oligodendroglial Kir4.1, uncovering a new role of OLs in regulating axonal glucose metabolism. Our findings reveal a novel model of axon-OL signaling and metabolic coupling in which OLs detect high-frequency axonal activity through K+ signaling, which is critical in adjusting the axon-OL metabolic unit and in preserving long-term axonal health.

neuroscience↗

bioRxiv2022

Deficiency in pericyte remodeling as a basis for impaired capillary flow and structure during brain aging

Deterioration of brain capillary flow and architecture is a hallmark of aging and dementia. It remains unclear how loss of brain pericytes in these conditions contributes to capillary dysfunction. Here, we conduct cause-and-effect studies by optically ablating pericytes in adult and aged mice in vivo. Focal pericyte loss induces capillary dilation without blood-brain barrier disruption. These abnormal dilations are exacerbated in the aged brain, and result in increased flow heterogeneity in capillary networks. A subset of affected capillaries experience reduced perfusion due to flow steal. Some capillaries stall in flow and regress, leading to loss of capillary connectivity. Remodeling of neighboring pericytes restores endothelial coverage and vascular tone within days. Pericyte remodeling is slower in the aged brain, resulting in regions of persistent capillary dilation. These findings link pericyte loss to disruption of capillary flow and structure. They also identify pericyte remodeling as a therapeutic target to preserve capillary flow dynamics.

neuroscience↗

bioRxiv2022

Myelin lipids as nervous system energy reserves

Neuronal functions and impulse propagation depend on the continuous supply of glucose1,2. Surprisingly, the mammalian brain has no obvious energy stores, except for astroglial glycogen granules3. Oligodendrocytes make myelin for rapid axonal impulse conduction4 and also support axons metabolically with lactate5-7. Here, we show that myelin itself, a lipid-rich membrane compartment, becomes a local energy reserve when glucose is lacking. In the mouse optic nerve, a model white matter tract, oligodendrocytes survive glucose deprivation far better than astrocytes, by utilizing myelin lipids which requires oxygen and fatty acid beta-oxidation. Importantly, fatty acid oxidation also contributes to axonal ATP and basic conductivity. This metabolic support by fatty acids is an oligodendrocyte function, involving mitochondria and myelin-associated peroxisomes, as shown with mice lacking Mfp2. To study reduced glucose availability in vivo without physically starving mice, we deleted the Slc2a1 gene from mature oligodendrocytes. This caused a significant decline of the glucose transporter GLUT1 from the myelin compartment leading to myelin sheath thinning. We suggest a model in which myelin turnover under low glucose conditions can transiently buffer axonal energy metabolism. This model may explain the gradual loss of myelin in a range of neurodegenerative diseases8 with underlying hypometabolism9.

neuroscience↗

bioRxiv2022

VRK1 is a Paralog Synthetic Lethal Target in VRK2-methylated Glioblastoma

Synthetic lethality -- a genetic interaction that results in cell death when two genetic deficiencies co-occur but not when either deficiency occurs alone -- can be co-opted for cancer therapeutics. A pair of paralog genes is among the most straightforward synthetic lethal interaction by virtue of their redundant functions. Here we demonstrate a paralog-based synthetic lethality by targeting Vaccinia-Related Kinase 1 (VRK1) in Vaccinia-Related Kinase 2 (VRK2)-methylated glioblastoma (GBM). VRK2 is silenced by promoter methylation in approximately two-thirds of GBM, an aggressive cancer with few available targeted therapies. Genetic knockdown of VRK1 in VRK2-null or VRK2-methylated cells results in decreased activity of the downstream substrate Barrier to Autointegration Factor (BAF), a regulator of post-mitotic nuclear envelope formation. VRK1 knockdown, and thus reduced BAF activity, causes nuclear lobulation, blebbing and micronucleation, which subsequently results in G2/M arrest and DNA damage. The VRK1-VRK2 synthetic lethal interaction is dependent on VRK1 kinase activity and is rescued by ectopic VRK2 expression. Knockdown of VRK1 leads to robust tumor growth inhibition in VRK2-methylated GBM xenografts. These results indicate that inhibiting VRK1 kinase activity could be a viable therapeutic strategy in VRK2-methylated GBM.

cancer biology↗

bioRxiv2021

Genome-wide analysis of long terminal repeat retrotransposons from the cranberry Vaccinium macrocarpon

BACKGROUNDLong terminal repeat (LTR) retrotransposons are widespread in plant genomes and play a large role in the generation of genomic variation. Despite this, their identification and characterization remains challenging, especially for non-model genomes. Hence, LTR retrotransposons remain undercharacterized in Vaccinium genomes, although they may be beneficial for current berry breeding efforts. OBJECTIVEExemplarily focusing on the genome of American cranberry (Vaccinium macrocarpon Aiton), we aim to generate an overview of the LTR retrotransposon landscape, highlighting the abundance, transcriptional activity, sequence, and structure of the major retrotransposon lineages. METHODSGraph-based clustering of whole genome shotgun Illumina reads was performed to identify the most abundant LTR retrotransposons and to reconstruct representative in silico full-length elements. To generate insights into the LTR retrotransposon diversity in V. macrocarpon, we also queried the genome assembly for presence of reverse transcriptases (RTs), the key domain of LTR retrotransposons. Using transcriptomic data, transcriptional activity of retrotransposons corresponding to the consensuses was analyzed. RESULTSWe provide an in-depth characterization of the LTR retrotransposon landscape in the V. macrocarpon genome. Based on 475 RTs harvested from the genome assembly, we detect a high retrotransposon variety, with all major lineages present. To better understand their structural hallmarks, we reconstructed 26 Ty1-copia and 28 Ty3-gypsy in silico consensuses that capture the detected diversity. Accordingly, we frequently identify association with tandemly repeated motifs, extra open reading frames, and specialized, lineage-typical domains. Based on the overall high genomic abundance and transcriptional activity, we suggest that retrotransposons of the Ale and Athila lineages are most promising to monitor retrotransposon-derived polymorphisms across accessions. CONCLUSIONSWe conclude that LTR retrotransposons are major components of the V. macrocarpon genome. The representative consensuses provide an entry point for further Vaccinium genome analyses and may be applied to derive molecular markers for enhancing cranberry selection and breeding.

plant biology↗

bioRxiv2021

ECCsplorer: a pipeline to detect extrachromosomal circular DNA (eccDNA) from next-generation sequencing data

MotivationExtrachromosomal circular DNAs (eccDNAs) are ring-like DNA structures physically separated from the chromosomes with 100 bp to several megabasepairs in size. Apart from carrying tandemly repeated DNA, eccDNAs may also harbor extra copies of genes or recently activated transposable elements. As eccDNAs occur in all eukaryotes investigated so far and likely play roles in stress, cancer, and aging, they have been prime targets in recent research - with their investigation limited by the scarcity of computational tools. ResultsHere, we present the ECCsplorer, a bioinformatics pipeline to detect eccDNAs in any kind of organism or tissue using next-generation sequencing techniques. Following Illumina-sequencing of amplified circular DNA (circSeq), the ECCsplorer enables an easy and automated discovery of eccDNA candidates. The data analysis encompasses two major procedures: First, read mapping to the reference genome allows the detection of informative read distributions including high coverage, discordant mapping, and split reads. Second, reference-free comparison of read clusters from amplified eccDNA against control sample data reveals specifically enriched DNA circles. Both software parts can be run separately or jointly, depending on the individual aim or data availability. To illustrate the wide applicability of our approach, we analyzed semiartificial and published circSeq data from the model organisms H. sapiens and A. thaliana, and generated circSeq reads from the non-model crop B. vulgaris. We clearly identified eccDNA candidates from all datasets, with and without reference genomes. The ECCsplorer pipeline specifically detected mitochondrial mini-circles and retrotransposon activation, showcasing the ECCsplorers sensitivity and specificity. The derived eccDNA targets are valuable for a wide range of downstream investigations - from analysis of cancer-related eccDNAs over organelle genomics to identification of active transposable elements. Availability and implementationThe ECCsplorer pipeline is available on GitHub at https://github.com/crimBubble/ECCsplorer under the GNU license. ContactTony Heitkam (tony.heitkam@tu-dresden.de) Supplementary informationSupplementary data are available online.

bioinformatics↗

bioRxiv2021

Comparative repeat profiling of two closely related conifers (Larix decidua and Larix kaempferi) reveals high genome similarity with only one fast-evolving satellite DNA

In eukaryotic genomes, cycles of repeat expansion and removal lead to large-scale genomic changes and propel organisms forward in evolution. However, in conifers, active repeat removal is thought to be limited, leading to expansions of their genomes, mostly exceeding 10 gigabasepairs. As a result, conifer genomes are largely littered with fragmented and decayed repeats. Here, we aim to investigate how the repeat landscapes of two related conifers have diverged, given the conifers accumulative genome evolution mode. For this, we applied low coverage sequencing and read clustering to the genomes of European and Japanese larch, Larix decidua (Lamb.) Carriere and Larix kaempferi (Mill.), that arose from a common ancestor, but are now geographically isolated. We found that both Larix species harbored largely similar repeat landscapes, especially regarding the transposable element content. To pin down possible genomic changes, we focused on the repeat class with the fastest sequence turnover: satellite DNAs (satDNAs). Using comparative bioinformatics, Southern, and fluorescent in situ hybridization, we reveal the satDNAs organizational patterns, their abundances, and chromosomal locations. Four out of the five identified satDNAs are widespread in the Larix genus, with two even present in the more distantly related Pseudotsuga and Abies genera. Unexpectedly, the EulaSat3 family was restricted to L. decidua and absent from L. kaempferi, indicating its evolutionarily young age. Taken together, our results exemplify how the accumulative genome evolution of conifers may limit the overall divergence of repeats after speciation, producing only few repeat-induced genomic novelties.

plant biology↗

bioRxiv2021

An fMRI-based brain marker predicts individual differences in delay discounting

Individual differences in impatience--how much we discount future compared to immediate rewards--are associated with general life outcomes and related to substance use, psychiatric diseases, and obesity. Here, we use machine-learning on fMRI activity during an intertemporal choice task to develop a brain marker of individual differences in delay discounting. Study 1 (N=110) was used as a training and cross-validation set, resulting in significant prediction accuracy (r = 0.49) and suggesting an interplay between brain regions associated with affect, value, and cognitive control. The validity of the brain marker was replicated in an independent data set (Study 2, N=145, r = 0.45). In both studies, responses of the marker significantly differed between overweight and lean individuals. This pattern is a first step towards a generalizable neuromarker of delay discounting and a potentially transdiagnostic phenotype, which can be used as a brain-based target measure in future studies.

neuroscience↗

bioRxiv2020

Broken, silent, and in hiding: Tamed endogenous pararetroviruses escape elimination from the genome of sugar beet (Beta vulgaris)

Background and AimsEndogenous pararetroviruses (EPRVs) are widespread components of plant genomes that originated from episomal DNA viruses of the Caulimoviridae family. Due to fragmentation and rearrangements, most EPRVs have lost their ability to replicate through reverse transcription and to initiate viral infection. Similar to the closely related retrotransposons, extant EPRVs were retained and often amplified in plant genomes for several million years. Here, we characterize the complete genomic EPRV fraction of the crop sugar beet (Beta vulgaris, Amaranthaceae) to understand how they shaped the beet genome and to suggest explanations for their absent virulence. MethodsUsing next- and third-generation sequencing data and the genome assembly, we reconstructed full-length in silico representatives for the three host-specific EPRV families (beetEPRVs) in the B. vulgaris genome. Focusing on the canonical family beetEPRV3, we investigated its chromosomal localization, abundance, and distribution by fluorescent in situ and Southern hybridization. Key ResultsBeetEPRVs range between 7.5 and 10.7 kb (0.3 % of the B. vulgaris genome) and are heterogeneous in structure and sequence. Although all three beetEPRV families were assigned to the florendoviruses, they showed variably arranged protein-coding domains, different degrees of fragmentation, and preferences for diverse sequence contexts. We observed small RNAs that target beetEPRVs in a family-specific manner, indicating stringent epigenetic suppression. We localized beetEPRV3 on all 18 sugar beet chromosomes, occurring preferentially in clusters and associated with heterochromatic, centromeric and intercalary satellite DNAs. BeetEPRV3 variants also exist in the genomes of related wild species, indicating an initial beetEPRV3 integration 13.4 to 7.2 million years ago. ConclusionsOur study in beet illustrates the variability of EPRV structure and sequence in a single host genome. Evidence of sequence fragmentation and epigenetic silencing imply possible plant strategies to cope with long-term persistence of EPRVs, including amplification, fixation in the heterochromatin, and containment of EPRV virulence.

plant biology↗

bioRxiv2020

Human induced pluripotent stem cell-derived arteries as personalized models of atherosclerosis on-a-chip

Atherosclerosis is an arterial disease characterized by intravascular plaques. Disease hallmarks are vessel stenosis and hyperplasia, eventually escalating into plaque rupture and acute clinical presentations. Innate immune cells and local variations in hemodynamics are core players in the pathology, but their mutual relationship has never been investigated before due to the lack of modeling systems with adequate degree of complexity. Here, we combined computational fluid dynamics and tissue-engineering to achieve, for the first time in vitro, full atherosclerotic plaque development. Our model incorporates induced pluripotent stem cell-derived populations into small-caliber arteries that are cultured in atheroprone conditions. Using machine-learning-aided immunophenotyping, molecular and nanoprobe-based tensile analyses, we found that immune cells, extracellular matrix components and tensional state were comparable between in vitro and ex vivo human lesions. Our results provide further insights into the relation between hemodynamics and inflammation, introducing a versatile, scalable modeling tool to study atherosclerosis onset and progression.

bioengineering↗

bioRxiv2020

Differential impact of GABAA Receptors on Inhibitory connectivity for Superficial Pyramidal Neuron Responsiveness In Vivo

A diverse set of GABAA receptors (GABAARs) enable synaptic plasticity adaptations at inhibitory postsynaptic sites in collaboration with the scaffolding protein gephyrin. Early studies helped to identify distinctions between GABAAR subtypes allocated within specific functional circuits, but their contribution to the changing dynamics of a microcircuit remains unclear. Here, using the whisker-barrel system in mouse, we assessed the contribution of specific synaptic GABAAR subtypes and gephyrin scaffolding changes to sensory processing in vivo. We monitored spontaneous and evoked Ca2+ transients in layer 2/3 pyramidal cells with the genetically encoded Ca2+ sensor RCaMP1.07. Using Gabra1 or Gabra2 global and conditional knockout mice, we uncovered that 1- and 2-GABAARs determine the sparseness of L2/3 pyramidal neuron encoding. In a cell-type dependent manner, 1-GABAARs and 2-GABAARs affected neuronal excitability and the reliability of neuronal responses after whisker stimulation. We also discerned that gephyrin with its diverse post-translational modifications (PTMs) shows preference for specific GABAAR subtype to facilitate microcircuit activity. Our results underscore the relevance of the diversity of GABAARs within a cortical microcircuit. Key pointsO_LIWhile GABAergic inhibition from interneuron subtypes regulates cortical microcircuit activity the molecular determinants have remain unclear. C_LIO_LIWe demonstrate that specific-GABAA receptor subtypes contribute differentially to layer 2/3 neuronal activities in mouse barrel cortex. C_LIO_LIImportantly, we link the GABAAR contributions to the scaffolding properties of its important postsynaptic density protein gephyrin. We show that different PTMs on gephyrin determines neuronal excitability via GABAAR recruitment and modulation of inhibition within layer 2/3 neurons. C_LIO_LISpecifically, 1 and 2 subunits containing GABAA receptors, along with their scaffolding protein gephyrin determine the distribution of high, medium and low activity pyramidal neurons during sensory encoding, whereby controlling the total activity of cortical microcircuit. C_LI

neuroscience↗

bioRxiv2020

Distinct signatures of calcium activity in brain pericytes

Even though pericytes have been implicated in various neurological disorders, little is known about their function and signaling pathways in the healthy brain. Here, we characterized cortical pericyte calcium dynamics using two-photon imaging of Pdgfr{beta}-CreERT2;GCaMP6s mice under anesthesia in vivo and in brain slices ex vivo. We found distinct differences between pericyte subtypes in vivo: Ensheathing pericytes exhibited smooth muscle cell-like calcium dynamics, while calcium signals in capillary pericytes were irregular, higher in frequency and occurred in cellular microdomains. In contrast to ensheathing pericytes, capillary pericytes retained their spontaneous calcium signals during prolonged anesthesia and in the absence of blood flow ex vivo. Chemogenetic activation of neurons in vivo and acute increase of extracellular potassium in brain slices strongly decreased calcium activity in capillary pericytes. We propose that neuronal activity-induced elevations in extracellular potassium suppress calcium activity in capillary pericytes, likely mediated by Kir2.2 and KATP channel activation.

neuroscience↗

bioRxiv2020

The severity of microstrokes depends on local vascular topology and baseline perfusion

1Cortical microinfarcts are caused by blood flow disturbances and are linked to pathologies like cerebral amyloid angiopathy and dementia. Despite their relevance for disease progression, microinfarcts often remain undetected and the smallest scale of disturbance has not yet been identified. We employ blood flow simulations in realistic microvascular networks from the mouse cortex to quantify the impact of single capillary occlusions. We reveal that the severity of a microstroke is strongly affected by the local vascular topology and the baseline flow rate in the occluded capillary. The largest changes in flow rate are observed in capillaries with two in- and two outflows. Interestingly, this specific topological configuration only occurs with a frequency of 8%, while the majority of capillaries are likely designed to efficiently supply oxygen and nutrients. Taken together, microstrokes likely induce a cascade of local disturbances in the surrounding tissue, which might accumulate and impair energy supply locally.

neuroscience↗

bioRxiv2020

A neural mechanism of social responsibility

This study investigated the neural mechanisms involved in feelings of interpersonal guilt and responsibility evoked by social decisions. In two studies (one during fMRI), participants repeatedly chose between safe and risky monetary outcomes in social contexts. Across conditions, each participant chose for both themselves and a partner (Social condition), or the partner chose for both themselves and the participant (Partner condition), or the participant chose just for themselves (Solo condition, control). If the risky option was chosen in the Social or Partner condition, participant and partner could each receive either the high or the low outcome of a lottery with 50% probability, independently of each other. Participants were shown the outcomes for themselves and for their partner on each trial, and reported their momentary happiness every few trials. As expected, participant happiness decreased following both low lottery outcomes for themselves and for the partner. Crucially, happiness decreases following low outcomes for the partner were larger when the participant rather than their partner had made the choice, which fits an operational definition of guilt. This guilt effect was associated with BOLD signal increase in the left anterior insula. Connectivity between this region and the right inferior frontal gyrus varied depending on choice and experimental condition, suggesting that this part of prefrontal cortex is sensitive to guilt-related information during social choices. Variations in happiness were well explained by computational models based on participants and partners rewards and reward prediction errors. A model-based analysis revealed a left superior temporal sulcus cluster that tracked partner reward prediction errors that followed participant choices. Our findings identify neural mechanisms of guilt and social responsibility during social decisions under risk.

neuroscience↗

bioRxiv2020

Respiratory and gut microbiota in commercial turkey flocks with disparate weight gain trajectories display differential compositional dynamics

Host-associated communities of bacteria (microbiota) substantially contribute to the overall poultry health and performance. Gut microbiota are known to play roles in resistance to pathogen infection and optimal weight gain in turkey flocks. However, knowledge of turkey respiratory microbiota and its link to gut microbiota is lacking. This study presents a 16S rRNA gene-based census of the turkey respiratory microbiota (nasal cavity and trachea) alongside gut microbiota (cecum and ileum) in two identical commercial Hybrid Converter turkey flocks raised in parallel under typical field commercial conditions. The flocks were housed in adjacent barns during the brood stage and in geographically separated farms during the grow-out stage. Several bacterial taxa that were acquired in the respiratory tract (RT) at the beginning of the brood stage persisted throughout the flock cycle, primarily Staphylococcus. Late-emerging predominant taxa in RT included Deinococcus and Corynebacterium. Tracheal and nasal microbiota of turkeys were identifiably distinct from one another and from gut microbiota. Nevertheless, gut and RT microbiota changed in parallel over time and appeared to share many taxa. During the brood stage, the two flocks generally acquired similar gut and RT microbiota, and their average body weights were comparable. Separating the flocks during the grow-out stage resulted in divergent microbial profiles and body weight gain trajectories. Lower weight gain corresponded with emergence of Deinococcus and Ornithobacterium in RT, and Fusobacterium and Parasutterella in gut. This study provides an overview of turkey microbiota under field conditions and suggests several hypotheses concerning the respiratory microbiome. IMPORTANCETurkey meat is an important source of animal protein, and the industry around its production contributes significantly to the agricultural economy. The nonpathogenic symbionts present in the gut of turkeys are known to impact bird health and flock performance. However, the respiratory microbiota in turkeys are entirely unexplored. This study has elucidated the microbiota of respiratory tracts of turkeys from two commercial flocks raised in parallel throughout a normal flock cycle. Further, the study suggests that bacteria originating in the gut or in poultry house environments may influence respiratory communities and consequently induce poor performance, either directly or indirectly. Future attempts to develop microbiome-based interventions for turkey health should delimit the contributions of respiratory microbiota and aim to limit disturbances to those communities.

microbiology↗