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Herzmann, C.

Publications and source records attributed to Herzmann, C..

5 recordsLinked to original sources

Longitudinal Dynamics and Site-Specific Recovery of the Human Respiratory Microbiome Following Smoking Cessation

BackgroundThe human respiratory tract harbours diverse microbial communities crucial for health, but their dynamics during environmental perturbations like smoking remain poorly understood. While smoking is a major risk factor for various diseases, its compartment-specific effects on the respiratory microbiome and potential recovery following cessation have not been fully elucidated. Here, we present a longitudinal, multi-site study of respiratory microbiome dynamics in smokers undergoing cessation, benchmarked against healthy never-smokers. MethodsUsing standardized sampling of the anterior nares, oropharynx, and bronchoalveolar lavage (BAL), combined with 16S rRNA gene amplicon sequencing and rigorous contamination controls, we characterized community composition, diversity, personalization, and microbial interactions across airway compartments. ResultsSmokers exhibited pronounced microbiome alterations: nasal richness increased, while lung richness and core taxa were reduced. Smoking-induced changes were compartment-specific and most pronounced in nose and lung. The degree of individuum-specific differences in community structure was elevated in smokers and correlated with smoking intensity and duration. Short-term cessation (6 weeks) led to minor shifts in taxa abundance but increased similarity between oropharyngeal and lung communities, whereas long-term cessation (1 year) resulted in partial restoration, particularly in lung and nasal microbiomes. Some taxa, including Haemophilus and Prevotella_7, showed persistent alterations, highlighting lasting smoking effects. Network analyses revealed that smoking disrupted microbial co-occurrence and reduced community connectivity, whereas cessation partially restored interaction networks, with dynamics differing between oropharynx and lung, reflecting different underlying ecological assembly processes. Recovery trajectories were highly individualized, with lung microbiomes influenced by deterministic processes and upper airway microbiomes shaped by stochastic factors, explaining site-specific responses and the persistence of personalized microbial signatures. ConclusionThese results provide the first time-resolved, multi-compartment characterization of respiratory microbiome recovery after smoking cessation, revealing that smoking leaves long-lasting, site-specific imprints on airway microbial communities and interactions. Our findings underscore the need for individual and compartment-specific approaches when designing microbiome-based interventions to support respiratory health.

microbiology↗

Lipobiotin-capture magnetic bead assay for isolation, enrichment and detection of Mycobacterium tuberculosis from saliva

BackgroundPulmonary Tuberculosis (TB) is diagnosed through sputum samples. As sputum sampling is challenging in children and cachexic patients, the development of diagnostic tests using saliva appears promising but has been discouraged due to low bacterial load and the poor sensitivity. We present a novel and rapid method to enrich Mycobacterium tuberculosis (Mtb) from saliva, which may serve as a basis for a diagnostic saliva test. MethodsLipobiotin-functionalized magnetic beads (LMBs) were incubated with Mtb-spiked PBS and saliva from healthy donors as well as with saliva from TB patients. Flow cytometry was used to evaluate the capacity of the beads to bind Mtb, while real-time quantitative polymerase chain reaction (qPCR) was utilized to detect Mtb and estimate the amount of mycobacterial DNA in different sample types. ResultsWe found that LMBs bind Mtb efficiently when compared to non-functionalized beads. The development of an qPCR assay based on the use of LMBs (LMB assay) allowed us to enrich mycobacterial DNA in spiked sample types, including PBS and saliva from healthy donors (enrichment of up to 8.7 fold). In Mtb-spiked saliva samples, we found that the LMB assay improved the detection rate of 102 bacteria in a volume of 5 ml from 0 out of 15 (0%) to 6 out of 15 (40%). Consistent with that, the LMB assay increased the rate of correctly identified saliva samples from TB patients in two independent cohorts. ConclusionsImplementation of the principle of the LMB-based assay may improve the sensitivity of existing diagnostic techniques, e.g. by functionalizing materials that facilitate Mtb sampling from the oral cavity.

microbiology↗

Tuberculostearic acid (TSA)-containing phosphatidylinositols as reliable marker to determine Mycobacterium tuberculosis bacterial burden

It is estimated that approximately one-fourth of the world's population is infected with strains of the Mycobacterium tuberculosis complex (MTBC), the causative agents of tuberculosis (TB). In this study, we present rationally developed molecular markers for bacterial burden, which are derived from mycobacterial phospholipids. Using lipidomic approaches, we show that tuberculostearic acid (TSA)-containing phosphatidylinositols (PI) are present in all clinically relevant MTBC lineages investigated. For the major abundant lipid PI 16:0_19:0 (TSA), a detection limit equivalent to 102 colony forming units (CFU) was determined for bacterial cultures and approximately 103 for cell culture systems. We further developed a mass spectrometry based targeted lipid assay, which - in contrast to bacterial quantification on solid medium - can be performed within several hours including sample preparation. Translation of this indirect and culture-free detection approach allowed the determination of pathogen loads in infected murine macrophages, human neutrophils and murine lung tissue. We show that marker lipids inferred from the mycobacterial PIs are increased in peripheral blood mononuclear cells (PBMCs) of TB patients beyond the lipid metabolic background in comparison to healthy controls. In a small cohort of drug-susceptible TB patients elevated levels of these marker molecules were detected at therapy start and declined following successful anti-tuberculosis treatment. The concentration of TSA-containing PIs can be used as correlate for reliable and rapid quantification of Mycobacterium tuberculosis (Mtb) burden in experimental in vitro model systems and may also provide a clinically relevant tool for monitoring TB therapy. One Sentence SummaryTuberculostearic acid containing phosphatidylinositols represent a novel, fast to measure, reliable correlate of Mycobacterium tuberculosis bacterial burden in experimental model systems, which makes a future clinical application conceivable.

biochemistry↗

Disruption to functional networks in neonates with perinatal brain injury predicts motor skills at 8 months

ObjectiveFunctional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. Methods: This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Infants (n=65, included in final analyses: n=53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 minutes of fcMRI acquired during natural sleep at term-equivalent age.\n\nResultsDisruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course.\n\nConclusionfcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.

neuroscience↗

Differences in the spatial and temporal patterns of head motion during MRI of adults and infants

AimHead motion has a profound effect on MRI, and will contaminate comparisons of function or structure between groups that move differently. This work compares adults and infants. Infants might move differently for physical, physiological and cognitive reasons, but so far these differences have not been quantified.\n\nMethodsThe spatial modes and total magnitude of motion in the MRI scanner were measured (N=211). The effects of group (infant vs. adult) and stimulation paradigm (auditory vs. visual) were evaluated.\n\nResultsSpatial modes of motion were found to be distinct between infant and adult groups. Infants had less anterior-posterior translational motion, but greater motion in other dimensions, often with complex multi-axis patterns. In magnitude distribution, sleeping infants often remained more still than adults, but when movement did occur it was more extreme and abrupt. Two groups of adults presented with different stimulation showed similar shapes of motion.\n\nConclusionThe spatial modes and magnitude distribution of motion differed substantially between groups, and must be considered carefully as a confound in comparisons of structure or function. The abruptness and magnitude of movement suggests that for infants relative to adults post-processing strategies such as de-noising are likely to be more effective than prospective motion correction.\n\nKey notesO_LIQuantified the spatial and temporal distribution of motion during MRI in 211 adults and neonates\nC_LIO_LIThe different spatial modes in adults and infants were visualized and statistically contrasted\nC_LIO_LIThe magnitude of motion had \"heavier tails\" in infants, with more still periods, and more large movements, than adults.\nC_LI

neuroscience↗