Biology subjects

Schmitt-Kopplin, P.

Publications and source records attributed to Schmitt-Kopplin, P..

9 recordsLinked to original sources

bioRxiv2026

Geographic and Climatic Origins Shape the Leaf Metabolome of Populus trichocarpa

O_LIBackground and Aims: Chemodiversity is a fitness-relevant trait shaped by genetics, environment, and their interaction. Populus trichocarpa naturally inhabits broad climatic gradients and shows extensive variation in specialised metabolism. We investigated whether provenance and climate of origin imprint leaf chemodiversity and class-level relationships under common-garden conditions, and how these patterns relate to gene expression. C_LIO_LIMethods: Leaves from 87 P. trichocarpa genotypes representing 22 provenances from the west coast of North America growing in a common garden were profiled by untargeted FT-ICR-MS (1030 features) and targeted LC-MS/MS. A subset of 41 genotypes was subject to RNA-seq analyses. We tested whether provenance influenced multivariate patterns and whether metabolomic differences were related to geographic and climatic distance, where chemodiversity was quantified as Functional Hill Diversity. C_LIO_LIKey Results: P. trichocarpa metabolomes differed among origins despite shared growth conditions and showed distance-decay with both geography and climate. North-south extremes were well separated, and within-drainage samples shared high similarity. Flavonoid and isoprenoid pools strongly co-varied across individuals, whereas isoprene synthase activity did not predict total isoprenoids. Transcriptomes showed within-pathway coherence but limited overall provenance separation. C_LIO_LIConclusions: Leaf chemistry in P. trichocarpa retains signatures of geographic origin even under common-garden conditions. Coordinated investment in flavonoids and isoprenoids, together with among-origin differences in functional chemodiversity, reveals provenance-linked chemical fingerprints that complement genomic and metabolic trait data for climate-informed deployment. C_LI

plant biology↗

bioRxiv2025

Glycosylated diterpenes associate with early containment of Fusarium culmorum infection across wheat (Triticum aestivum L.) genotypes under field conditions

Wheat (Triticum aestivum L.) is severely affected by head blight, a destructive disease caused primarily by Fusarium species, which reduces yield and contaminates grains with trichothecene mycotoxins that compromise food and feed safety worldwide. Mechanistic insights into host-pathogen interactions have largely emerged from controlled experimental settings, providing conceptual foundations under conditions of constrained genetic and environmental complexity. Resolving consistent, generalizable molecular patterns across diverse wheat genotypes within a large-scale, heterogeneous field study remains technically and methodologically challenging. Addressing this gap, we integrated quantitative mycotoxin profiling with untargeted metabolomics in a field experiment comprising 105 wheat genotypes deliberately inoculated with F. culmorum, with the goal of identifying molecular signatures of infection and containment under realistic agronomic conditions. Quantified deoxynivalenol (DON) concentrations provided a robust, continuous measure of infection intensity, enabling metabolite profiles to be related directly to pathogen activity beyond the limitations of symptom-based visual scoring. Consistent with established Fusarium trichothecene biosynthesis, sesquiterpene-derived metabolites closely tracked toxin accumulation, thereby recapitulating infection-associated metabolic patterns across the large-scale field study. Conversely, glycosylated diterpene conjugates were elevated under low toxin accumulation, linking their abundance to contained Fusarium pathogen activity and highlighting a largely underexplored aspect of wheat metabolism in host-pathogen interactions. Elucidating their biosynthetic origin, enzymatic interconversion, and regulatory context will be key to defining potential diterpene-associated defense processes across wheat genotypes.

plant biology↗

bioRxiv2025

Long-Term Intestinal Epithelial Remodeling Induced by Acute Protein-Energy Malnutrition

Protein-energy malnutrition (PEM) is a global health burden with lasting effects that extend well beyond the initial nutrient deficiency. To systematically investigate the long-term effects of a single episode of PEM on the structure and function of the intestinal epithelium and its associated microbiota, we employed a comprehensive multi-omics approach, including (spatial) transcriptomics, DNA methylation analysis, fecal metagenomics, and metabolomics. Our findings show that PEM persistently alters the intestinal epithelium by depleting Paneth cells and suppressing antimicrobial gene expression - changes linked to DNA methylation that persist despite dietary recovery. In germ-free mice, the sustained epithelial phenotype after was absent. We identified the microbial lipid metabolite 9-HODE and epigenetically deregulated PPAR-driven GDF15 expression as key molecular drivers of the persistent PEM-induced Paneth cell dysfunction. Targeting microbial lipid production and its link to the host GDF15 pathway could offer novel therapeutic strategies for long-term consequences of malnutrition and other Paneth cell-associated diseases.

immunology↗

bioRxiv2025

Multi-omics analysis highlights the link of aging-related cognitive decline with systemic inflammation and alterations of tissue-maintenance

Aging-related cognitive decline is associated with changes across different tissues and the gut microbiome, including dysfunction of the gut-brain axis. However, only few studies have linked multi-organ alterations to cognitive decline during aging. Here we report a multi-omics analysis integrating metabolomics, transcriptomics, DNA methylation, and metagenomics data from hippocampus, liver, colon, and fecal samples of mice, correlated with cognitive performance in the Barnes Maze spatial learning task across different age groups. We identified 734 molecular features associated with cognitive rank within individual data layers, of which 227 features remain when integrating all data layers with each other. Among the single-layer predictors, several host and microbial features were highlighted, with host-associated markers being predominant. Host features associated with cognitive function mainly belong to innate and adaptive inflammatory activity (inflammaging) and developmental processes. Our findings suggest that cognitive decline in aging is tightly coupled to systemic, age-associated inflammation, potentially initiated by microbiome-driven gastrointestinal inflammatory activity, emphasizing a link between peripheral tissue alterations and brain function.

systems biology↗

bioRxiv2024

Metabolic modeling reveals the aging-associated decline of host-microbiome metabolic interactions in mice

Aging is the predominant cause of morbidity and mortality in industrialized countries. The specific molecular mechanisms that drive aging are poorly understood, especially the contribution of the microbiota in these processes. Here, we combined multi-omics with metabolic modeling in mice to comprehensively characterize host-microbiome interactions and how they are affected by aging. Our findings reveal a complex dependency of host metabolism on microbial functions, including previously known as well as novel interactions. We observed a pronounced reduction in metabolic activity within the aging microbiome, which we attribute to reduced beneficial interactions in the microbial community and a reduction in its metabolic output. These microbial changes coincided with a corresponding downregulation of key host pathways predicted by our model to be dependent on the microbiome that are crucial for maintaining intestinal barrier function, cellular replication, and homeostasis. Our results elucidate microbiome-host interactions that potentially influence host aging processes, focusing on microbial nucleotide metabolism as a pivotal factor in aging dynamics. These pathways could serve as future targets for the development of microbiome-based therapies against aging. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/587009v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@a8e7faorg.highwire.dtl.DTLVardef@115f35aorg.highwire.dtl.DTLVardef@1bbf32org.highwire.dtl.DTLVardef@1a58c7f_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2022

Cell wall strengthening by phenylpropanoid dehydrodimers during the plant hypersensitive cell death

Infection of Arabidopsis with avirulent Pseudomonas syringae and exposure to nitrogen dioxide (NO2) both trigger hypersensitive cell death (HCD) that is characterized by the emission of bright blue-green (BG) autofluorescence under UV illumination. The aim of our current work was to identify the BG fluorescent molecules and scrutinize their biosynthesis and functions during the HCD. Compared to wild-type (WT) plants, the phenylpropanoid-deficient mutant fah1 developed normal HCD except for the absence of BG fluorescence. Ultrahigh resolution metabolomics combined with mass difference network analysis revealed that WT but not fah1 plants rapidly accumulate dehydrodimers of sinapic acid, sinapoylmalate, 5-OH-ferulic acid, and 5-OH-feruloylmalate during the HCD. FAH1-dependent BG fluorescence appeared exclusively within dying cells of the upper epidermis as detected by microscopy. Saponification released dehydrodimers from extracted cell wall material. Collectively, our data suggest that HCD induction leads to the formation of free BG fluorescent dehydrodimers from monomeric sinapates and 5-hydroxyferulates. Reactive oxygen species from de-regulated photosynthesis likely contribute to the radical-radical coupling. The formed dehydrodimers move from upper epidermis cells into the apoplast where they esterify and thereby cross-link cell wall polymers. Both, free as well as wall-bound phenylpropanoid dehydrodimers are defense-related compounds in Arabidopsis. We propose that other plants also employ dehydrodimers of highly abundant phenylpropanoids for rapid defense against pathogen attack.

plant biology↗

bioRxiv2022

Farnesoid X Receptor suppresses lipid peroxidation and ferroptosis

ObjectiveFerroptosis is a regulated cell death modality that occurs upon iron-dependent lipid peroxidation. The recent decade of research has uncovered many regulators driving ferroptosis as well as cellular gatekeepers preventing ferroptosis. Yet, many processes and networks remain to be elucidated. Methods and resultsIn this study, we performed a chemical screen using small molecules with known mode of action and identified two agonists (Turofexorate and Fexaramine) of the nuclear receptor Farnesoid X Receptor (FXR), also known as NR1H4, to suppress ferroptosis, but not apoptosis or necroptosis. Further, we demonstrate that in liver cells with high FXR protein levels, inhibition of FXR sensitizes cells to undergo ferroptotic cell death, while activation of FXR inhibits ferroptosis. Importantly, FXR also inhibits ferroptosis in ex vivo primary mouse hepatocytes. Activation of FXR by Turofexorate and Fexaramine significantly reduces lipid peroxidation. Mechanistically, overexpression of FXR or activation of FXR by bile acids upregulates the ferroptosis-inhibitory regulators FSP1, PPAR, GPX4, SCD1, and ACSL3 to reduce peroxidized lipids and to counteract ferroptosis. ConclusionIn this study, we demonstrate that activation of FXR inhibits ferroptotic cell death via upregulation of a number of ferroptosis-inhibitory proteins (FSP1, PPAR, GPX4, SCD1, and ACSL3) to reduce lipid peroxidation. Hence, modulating FXR activity may be beneficial to overcome ferroptosis-mediated degenerative diseases.

cell biology↗

bioRxiv2020

Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis

Hexokinases (HK) catalyze the first step of glycolysis and thereby limit its pace. HK2 is highly expressed in the gut epithelium, plays a role in immune responses and is upregulated in inflammation and ulcerative colitis 1-3. Here, we examined the microbial regulation of HK2 and its impact on intestinal inflammation by generating mice lacking HK2 specifically in intestinal epithelial cells (Hk2{Delta}IEC). Hk2{Delta}IEC mice were less susceptible to acute intestinal inflammation upon challenge with dextran sodium sulfate (DSS). Analyzing the epithelial transcriptome from Hk2{Delta}IEC mice during acute colitis revealed downregulation of cell death signaling and mitochondrial dysfunction dependent on loss of HK2. Using intestinal organoids derived from Hk2{Delta}IEC mice and Caco-2 cells lacking HK2, we identified peptidyl-prolyl cis-trans isomerase (PPIF) as a key target of HK2-mediated regulation of mitochondrial permeability and repression of cell-death during intestinal inflammation. The microbiota strongly regulated HK2 expression and activity. The microbially-derived short-chain fatty acid (SCFA) butyrate repressed HK2 expression and oral supplementation protected wildtype but not Hk2{Delta}IEC mice from DSS colitis. Our findings define a novel mechanism how butyrate may act as a protective factor for intestinal barrier homeostasis and suggest targeted HK2 inhibition as a promising therapeutic avenue in intestinal inflammation.

immunology↗

bioRxiv2020

Longitudinal profiles of dietary and microbial metabolites in formula- and breastfed infants

The early-life metabolome of the intestinal tract is dynamically influenced by colonization of gut microbiota which in turn is affected by nutrition, i.e. breast milk or formula. A detailed examination of fecal metabolites was performed to investigate the effect of probiotics in formula compared to control formula and breast milk within the first months of life in healthy neonates. A broad metabolomics approach was conceptualized to describe fecal polar and semi-polar metabolites affected by diet within the first year of life. Fecal metabolomes were clearly distinct between formula- and breastfed infants, mainly originating from diet and microbial metabolism. Unsaturated fatty acids and human milk oligosaccharides were increased in breastfed, whereas Maillard products were found in feces of formula-fed children. Altered microbial metabolism was represented by bile acids and aromatic amino acid metabolites. Elevated levels of sulfated bile acids were detected in stool samples of breastfed infants, whereas secondary bile acids were increased in formula-fed infants. Co-microbial metabolism was supported by significant correlation between chenodeoxycholic or lithocholic acid and members of Clostridia. Fecal metabolites showed strong inter- and intra-individual behavior with features uniquely present in certain infants and at specific time points. Nevertheless, metabolite profiles converged at the end of the first year, coincided with solid food introduction.

biochemistry↗