A5026315888- Gut microbiota and health
- Diet and metabolism studies
- Digestive system and related health
- Tryptophan and brain disorders
- Genetics, Aging, and Longevity in Model Organisms
- SARS-CoV-2 and COVID-19 Research
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Diabetes and associated disorders
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Cancer-related molecular mechanisms research
- Ferroptosis and cancer prognosis
- COVID-19 Clinical Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Chemical Reactions and Isotopes
- GABA and Rice Research
- Ginger and Zingiberaceae research
- Stress Responses and Cortisol
- Bacteriophages and microbial interactions
- Plant and Fungal Interactions Research
- Genomics and Chromatin Dynamics
- Computational Drug Discovery Methods
- Single-cell and spatial transcriptomics
University Hospital Schleswig-Holstein
2022-2025
University of Lübeck
2022-2025
Kiel University
2018-2025
Metformin is the first-line therapy for treating type 2 diabetes and a promising anti-aging drug. We set out to address fundamental question of how gut microbes nutrition, key regulators host physiology, affect effects metformin. Combining two tractable genetic models, bacterium E. coli nematode C. elegans, we developed high-throughput four-way screen define underlying host-microbe-drug-nutrient interactions. show that integrate cues from metformin diet through phosphotransferase signaling...
Abstract Background The interplay of epigenetic processes and the intestinal microbiota may play an important role in development homeostasis. Previous studies have established that regulates a large proportion epithelial transcriptome adult host, but microbial effects on DNA methylation gene expression during early postnatal are still poorly understood. Here, we sought to investigate cells (IECs) development. Methods We collected IECs from small intestine each five 1-, 4- 12 16-week-old...
High-sugar diets cause thirst, obesity, and metabolic dysregulation, leading to diseases including type 2 diabetes shortened lifespan. However, the impact of obesity water imbalance on health survival is complex difficult disentangle. Here, we show that high sugar induces dehydration in adult Drosophila, supplementation fully rescues their Conversely, defects are water-independent, showing uncoupling between sugar-induced insulin resistance with reduced vivo. promote accumulation uric acid,...
Abstract Although DNA methylation data yields highly accurate age predictors, little is known about the dynamics of this quintessential epigenomic biomarker during lifespan. To narrow gap, we investigate trajectories male mouse colon at five different time points aging. Our study indicates existence sudden hypermethylation events specific stages life. Precisely, identify two switches early-to-midlife (3-9 months) and mid-to-late-life (15-24 transitions, separating rodents’ life into three...
A metabolic switch favoring glycolysis over aerobic oxidative phosphorylation, termed the "Warburg effect", is a hallmark of cancer cells [1]. Hexokinase (HK) catalyzes first and irreversible step glycolysis, thereby limiting overall glycolytic activity. Mammals encode five HK family members: HK1-4 HKDC1 (HK domain containing 1). has an exceptionally low glucose affinity and, therefore, hexokinase activity under physiological conditions [2], raising questions about its function. recent study...
Abstract Aging is accompanied by considerable changes in the gut microbiome, yet molecular mechanisms driving aging and role of microbiome remain unclear. Here we combined metagenomics, transcriptomics metabolomics from mice with metabolic modelling to characterize host–microbiome interactions during aging. Reconstructing integrated models host 181 mouse microorganisms, show a complex dependency metabolism on known previously undescribed microbial interactions. We observed pronounced...
Abstract Background Alterations in the composition and function of intestinal microbiota have been observed organismal aging across a broad spectrum animal phyla. Recent findings, which derived mostly simple models, even established causal relationship between age-related microbial shifts lifespan, suggesting microbiota-directed interventions as potential tool to decelerate processes. To test whether life-long microbiome rejuvenation strategy could delay or prevent non-ruminant mammals, we...
Cognitive decline is one of the greatest health threats old age and maintenance optimal brain function across a lifespan remains big challenge. The hippocampus considered particularly vulnerable but there cross-species consensus that its functional integrity benefits from early continuous exercise demanding physical, social mental activities, also referred to as environmental enrichment (EE). Here, we investigated extent which late-onset EE can improve already-impaired cognitive abilities...
Parkinson’s disease (PD) is a chronic and progressive neurodegenerative with the major symptoms comprising loss of movement coordination (motor dysfunction) non-motor dysfunction, including gastrointestinal symptoms. Alterations in gut microbiota composition have been reported PD patients vs. controls. However, it still unclear how these compositional changes contribute to etiology progression. Furthermore, most available studies focused on European, Asian, North American cohorts, but...
Aging is the predominant cause of morbidity and mortality in industrialized countries. The specific molecular mechanisms that drive aging are poorly understood, especially contribution microbiota these processes. Here, we combined multi-omics with metabolic modeling mice to comprehensively characterize host-microbiome interactions how they affected by aging. Our findings reveal a complex dependency host metabolism on microbial functions, including previously known as well novel interactions....
Understanding how the microbiota produces regulatory metabolites is of significance for cancer and therapy. Using a host-microbe-drug-nutrient 4-way screening approach, we evaluated role nutrition at molecular level in context 5-fluorouracil toxicity. Notably, our screens identified metabolite 2-methylisocitrate which was found to be produced enriched human tumor-associated microbiota. exhibits anti-proliferative properties across genetically- tissue-diverse cell lines, 3D spheroids, an vivo...
Inflammation is considered a possible cause of cognitive decline during aging. This study investigates the influence physical activity and social isolation in old mice on their functions inflammation. The Barnes maze task was performed to assess spatial learning memory 3, 9, 15, 24, 28 months male C57BL/6 as well following voluntary wheel running (VWR) (SI) 20 mice. Inflammatory gene expression analyzed hippocampal colonic samples by qPCR. Cognitive occurs between 15 24 age. VWR improved...
Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this we predicted capacity of cells sustain virion production in patients and found tissue-wide induction metabolic pathways that support replication. Expanding our analysis influenza A dengue viruses, identified targets inhibitors potential broad-45 spectrum treatment....
The SARS-CoV-2 pandemic has reemphasized the urgent need to develop broad-spectrum antiviral therapies. Wedeveloped a computational pipeline that uses scRNA-Seq data reconstruct metabolic state of cells and tissuesduring viral infection. Using this pipeline, we investigated cellular capacity produce virions invarious tissues disease conditions. Subsequently, expanded our analysis influenza A dengue virus andidentified several targets their inhibitors for treatment. Phenformin, an inhibitorof...
Abstract:The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational pipeline using scRNA-Seq data to assess cellular metabolism during viral infection. With this we predicted capacity of cells sustain virion production in patients and found tissue-wide induction metabolic pathways that support replication. Expanding our analysis influenza A dengue viruses, identified targets inhibitors potential treatment. These were highly...
Abstract The pandemic spread of the potentially life-threatening disease COVID-19 requires a thorough understanding longitudinal dynamics host responses. Temporal resolution cellular features associated with severe trajectory will be pre-requisite for finding outcome predictors. Here, we performed multi-omics study using two-centre German cohort 13 patients (from Cologne and Kiel, 1). We analysed bulk transcriptome, DNA methylome, single-cell transcriptome (>358,000 cells, including BCR...
Abstract Background A metabolic switch favoring glycolysis over aerobic oxidative phosphorylation, namely the “Warburg effect”, represents a hallmark of cancer cells. Hexokinases (HK) catalyze first step glycolysis, thereby regulating its rate. Dysregulated HKDC1 (HK domain containing 1) expression has been associated with various types and blocking prevents disease progression for hepatic carcinoma T cell lymphoma lung adenocarcinoma, but implication colorectal (CRC) remained unknown. Here,...