Biology subjects

Sturm, S.

Publications and source records attributed to Sturm, S..

7 recordsLinked to original sources

bioRxiv2025

Longitudinal multi-omic evaluation of biomarkers of health and ageing over smoking cessation intervention

Smoking is one of the single most important preventable risk factors for cancer and other adverse health outcomes 1,2. Smoking cessation represents a key public health intervention with the potential to reduce its negative health outcomes 2-4. While epidemiological, cross-sectional, and individual longitudinal omic or biomarker studies have evaluated the impact of smoking cessation, no study to date has systematically profiled molecular and clinical changes in several organ systems or tissues longitudinally over the course of smoking cessation that could allow for more detailed assessment of response biomarkers and the identification of interindividual differences in the recovery of physiological functions. Here, we report the first human longitudinal multi-omic study of smoking cessation, evaluating 2,501 unique single or composite features from 1,094 longitudinal samples. Our comprehensive analysis, leveraging over half a million longitudinal data points, revealed a profound effect of smoking cessation on epigenetic biomarkers and microbiome features across multiple organ systems within 6 months of smoking cessation, alongside shifts in the immune and blood oxygenation system. Moreover, our multi-omic analysis provided unprecedented granularity that allows for identification of new cross-ome associations for mechanistic discovery. We anticipate that data and an interactive app from the Tyrol Lifestyle Atlas (eutops.github.io/lifestyle-atlas), comprising the current study and a parallel study arm evaluating the impact of diet on biomarkers of health and disease, will provide the basis for future discovery, biomarker benchmarking in their responsiveness to health-promoting interventions, and study of individualised response group, representing a major advance for personalised health monitoring using biomarkers.

systems biology↗

bioRxiv2025

Systemic multi-omic remodelling underlies health benefits of intermittent fasting

While intermittent fasting (IF) promotes longevity in animal models, its systemic effects in humans remain poorly understood. Here, we present a six-month longitudinal IF intervention in 114 women (BMI 25-35) with deep clinical, molecular, and microbiome profiling across >3,400 biospecimens from six tissues. Analyses spanning >2,200 multi-omic features and 11,000 microbial function predictions demonstrate coordinated clinical benefits, including improvements in body composition and cardiorespiratory fitness, and reveal coordinated molecular responses across tissues. Iron metabolism emerged as a central axis: transferrin increased while ferritin, haemoglobin, and erythrocytes decreased, changes that opposed ageing trajectories yet remained within physiological limits. Epithelial DNA methylation biomarkers (cervical, buccal) of cancer risk reduced, while blood clocks were largely unresponsive, underscoring tissue-specificity of the epigenome. Immune profiling uncovered dynamic, partially reversible shifts. Notably, we derived a new immunophenotyping-based ImmuneAge score that increased during fasting and tracked with inflammatory function, while the pro-inflammatory cytokine IL-17A declined selectively in postmenopausal women. Oral microbiota showed rapid restructuring, whereas gut microbiota shifted more subtly toward enhanced metabolic capacity. Together, these data provide unprecedented insight into the systemic and tissue-specific responses to IF in humans and identify iron homeostasis and immune remodelling as candidate mechanisms. Our findings are available through the Lifestyle Atlas (https://eutops.github.io/lifestyle-atlas). HighlightsO_LIIntermittent fasting remodels iron metabolism, opposing age-associated trajectories C_LIO_LIEpithelial but not blood methylation biomarkers respond to fasting C_LIO_LIFasting transiently elevates ImmuneAge and TNF-producing cytotoxic T cells C_LIO_LIOral microbiota restructure rapidly, while gut microbiota show subtler functional shifts C_LIO_LIIntegrative networks link iron, immunity, adiposity, and epithelial barrier function C_LI

systems biology↗

bioRxiv2025

Multi-modal atlas of lifestyle interventions reveals malleability of ageing-linked molecular features

Extending human healthspan requires understanding how lifestyle interventions impact molecular systems across tissues and time. Here, we present the TirolGESUND Lifestyle Atlas (ClinicalTrials.gov: NCT05678426), a longitudinal, multi-modal resource profiling 156 healthy women (aged 30-60 years) undergoing 6-month intermittent fasting (n=114) or smoking cessation (n=42) interventions. Participants were sampled up to four times across seven tissues and fluids, generating >3,450 biospecimens with harmonised DNA methylation, metabolomics, microbiome, and immune profiling, alongside skin histology, barrier measurements, and rich clinical metadata. We demonstrate the utility of this dataset through: (i) multi-omics-wide association studies linking traits to molecular features; (ii) integrative factor modelling revealing coordinated cross-tissue signatures; (iii) epigenetic-biomarker cross-omic associations, and (iv) CpG-level variance decomposition mapping stable, individual-specific, tissue-restricted, and intervention-responsive methylation patterns. We further show that ageing-linked features are selectively malleable: highly compliant intermittent fasting participants exhibited attenuated or even age-opposing molecular trajectories within six months. The atlas enables unprecedented within-cohort comparisons across omic layers and tissues, supporting discovery of context-dependent biomarkers, cross-system coordination, and intervention responsiveness. Data are available via an interactive portal, with sensitive data under controlled access (https://eutops.github.io/lifestyle-atlas/). This resource provides a foundation for exploring biomarker association and multi-tissue epigenetics, enabling hypothesis generation and benchmarking for systems biology and human healthspan research. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=186 HEIGHT=200 SRC="FIGDIR/small/673115v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@fec2d9org.highwire.dtl.DTLVardef@1aa5d13org.highwire.dtl.DTLVardef@1c4a6f2org.highwire.dtl.DTLVardef@1ac62fb_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIMulti-tissue multi-modal profiling of two clinically-relevant lifestyle interventions in 156 women aged 30-60 C_LIO_LIIntermittent fasting modifies ageing-linked molecular features in an age-opposing direction C_LIO_LICross-tissue epigenetic biomarker mapping links immunity, metabolism, and microbiome C_LIO_LITissue-specific epigenetic plasticity maps reveal candidate meQTLs, C_LIO_LIData sharing and interactive portal enable broad reuse for hypothesis generation and exploration C_LI

systems biology↗

bioRxiv2023

Microbe-induced plant resistance against insect pests depends on timing of inoculation, but is consistent across climatic conditions

O_LITo cope with abiotic and biotic stressors, plants have developed mutualistic associations with beneficial soil microbes, but little is known about how (extreme) abiotic conditions impact on microbe-induce resistance to insect herbivores. C_LIO_LIExtreme temperatures are often accompanied by extremes in plant water availability, which together reduce plant growth and change plant physiology. There are potential consequences for increasing plant susceptibility to biotic stresses, and this poses a real challenge for plant productivity. C_LIO_LIWe evaluated how the effects of beneficial soil bacteria (Acidovorax radicis) on barley plant growth and resultant resistance against aphid infestation (Sitobion avenae) were impacted by a single heatwave event across a plant water availability gradient. We also tested if timing of bacterial inoculation (before or after the heatwave) affected bacteria-plant interactions on aphids. C_LIO_LIWe found that heatwaves affected plant biomass allocation from aboveground to belowground tissues. Inoculation with A. radicis led to reduction of aphid numbers, but depended on timing of inoculation, and led to stronger resistance when inoculations occurred closer to aphid infestation. Remarkably, microbe-induced resistance against aphids was consistent across heatwave and water availability treatments. C_LIO_LIThis study provides evidence that beneficial plant-bacteria interactions may represent a potential solution for sustainable agricultural practices to enhance plant growth and response to insect pests under climate change. Future field trials should investigate the consistency of beneficial effects reported here for a better understanding of multispecies interactions in the context of global change. C_LI

ecology↗

bioRxiv2023

Floral presence and flower identity alter cereal aphid endosymbiont communities on adjacent crops

O_LIFloral plantings adjacent to crops fields can recruit populations of natural enemies by providing flower nectar and non-crop prey to increase natural pest regulation. Observed variation in success rates might be due to changes in the unseen community of protective endosymbionts hosted by many herbivorous insects, which can confer resistance to various specialist natural enemies, e.g. parasitoid wasps. Reduced insect control may occur if highly protective symbiont combinations increase in frequency via selection effects, and this is expected to be stronger in lower diversity systems. C_LIO_LIWe used a large-scale field trial to analyse the bacterial endosymbiont communities hosted by cereal aphids (Sitobion avenae) collected along transects into strip plots of barley plants managed by either conventional or integrated (including floral field margins and reduced inputs) methods. In addition, we conducted an outdoor pot experiment to analyse endosymbionts in S. avenae aphids collected on barley plants that were either grown alone or alongside one of three flowering plants, across three time points. C_LIO_LIIn the field, aphids hosted up to four symbionts. The abundance of aphids and parasitoid wasps was reduced towards the middle of all fields while aphid symbiont species richness and diversity decreased into the field in conventional, but not integrated, field-strips. The proportion of aphids hosting different symbiont combinations varied across cropping systems, with distances into the fields, and were correlated with parasitoid wasp abundances. C_LIO_LIIn the pot experiment, aphids hosted up to six symbionts. Flower presence increased natural enemy abundance and diversity, and decreased aphid abundance. The proportion of aphids hosting different symbiont combinations varied across the flower treatment and time, and were correlated with varying abundances of the different specialist parasitoid wasp species recruited by different flowers. C_LIO_LISynthesis and applications. Floral plantings and flower identity can have community-wide impacts on the combinations of bacterial endosymbionts hosted by herbivorous insects. Our work highlights the potential of within-season selection for symbiont-mediated pest resistance to natural enemies with biological control impacts. This could be mitigated through increased recruitment of diverse natural enemies by incorporating functional diversity of floral resources into the environment. C_LI

ecology↗

bioRxiv2022

Part-night exposure to artificial light at night has more detrimental effects on aphid colonies than fully lit nights

Artificial light at night (ALAN) threatens natural ecosystems globally. While ALAN research is increasing, little is known about how ALAN affects plants and interactions with other organisms. We explored the effects of ALAN on plant defence and plant-insect interactions using barley (Hordeum vulgare) and the English grain aphid (Sitobion avenae). Plants were exposed to full or part nights of 15-20 lux ALAN, or no ALAN control nights, to test the effects of ALAN on plant growth and defence. Although plant growth was only minimally affected by ALAN, aphid colony growth and aphid maturation were reduced significantly by ALAN treatments. Importantly, we found strong differences between full-night and part-night ALAN treatments. Contrary to our expectations, part ALAN had stronger negative effects on aphid colony growth than full ALAN. Defence-associated gene expression was affected in some cases by ALAN, but also positively correlated with aphid colony size, suggesting that the effects of ALAN on plant defences are indirect, and regulated via direct disruption of aphid colonies, rather than via ALAN-induced upregulation of defences. Mitigating ecological side effects of ALAN is a complex problem, as reducing exposure to ALAN increased its negative impact on insect herbivores.

ecology↗

bioRxiv2019

7q11.23 Syndromes Reveal BAZ1B as a Master Regulator of the Modern Human Face and Validate the Self-Domestication Hypothesis

Symmetrical 7q11.23 dosage alterations cause craniofacial and cognitive/behavioral phenotypes that provide a privileged entry point into the evolution of the modern human face and (pro-) sociality. We undertook a functional dissection of chromatin remodeler BAZ1B in neural crest stem cells (NCSCs) from a uniquely informative cohort of typical and atypical patients harboring 7q11.23 Copy Number Variants (CNVs). Our results reveal a key contribution of BAZ1B to NCSC in vitro induction and migration, coupled with a crucial involvement in neural crest (NC)-specific transcriptional circuits and distal regulation. By intersecting our experimental data with new paleogenetic analyses comparing modern and archaic humans, we uncover a modern-specific enrichment for regulatory changes both in BAZ1B and its experimentally defined downstream targets, thereby providing the first empirical validation of the self-domestication hypothesis and positioning BAZ1B as a master regulator of the modern human face.\n\nOne Sentence SummaryBAZ1B dosage shapes the modern human face.

evolutionary biology↗