Biology subjects

Taubenheim, J.

Publications and source records attributed to Taubenheim, J..

11 recordsLinked to original sources

bioRxiv2026

Microbial genome functions explain metabolite-driven dysbiosis and Pseudomonas-associated ammonium toxicity in Hydra

Host-associated microbiomes are typically maintained in stable configurations that support host fitness, yet the mechanisms by which metabolic perturbations destabilize these communities remain poorly understood. Using the freshwater cnidarian Hydra vulgaris AEP, we systematically assessed microbiome responses to 326 single-metabolite perturbations. Only 17 metabolites, mostly amino acid-related compounds, induced significant compositional shifts in the microbial community. Most shifts are accompanied by transitions from Curvibacter- to Pseudomonas-dominated or Legionella-dominated states, indicating the existence of three alternative community states which can be induced by metabolic triggers. Integrating 16S sequences with functional genomic information, we found that {beta}-diversity strongly predicted functional shifts, whereas reduced -diversity was associated with loss of metabolic functions. The metabolite perturbations also altered host-microbe interactions, affecting pathogenicity-, glycocalyx-, and nitrogen-related functions. In particular, nitrogen metabolism shifted from ammonia oxidation in Curvibacter-dominated communities to ammonia reduction in Pseudomonas-dominated states. Experimental validation confirmed that Pseudomonas metabolizes L-arginine and drives environmental ammonia accumulation to levels that could impair Hydras fitness and induce disease phenotypes. Conversely, Limnobacter was found to scavenge the environmental ammonia, potentially mitigating the adverse effects. These results demonstrate that metabolite-driven niche reconfiguration can destabilize host-associated microbiomes by coupling compositional shifts to functional change and host pathology, identifying metabolite-driven niche restructuring as a mechanism linking microbial community instability to host dysfunction.

microbiology↗

bioRxiv2026

Variation in gut microbiome diversity and structure across host lifestyles in Thailand

Global comparisons have revealed marked shifts in gut microbiome diversity and composition with industrialization and urbanization. Whether such changes also arise at finer geographical scales, among neighboring populations adopting different lifestyles, remains largely unexplored. In this study, we characterized the gut microbiomes of Thai populations with distinct lifestyles: urban residents from Bangkok, farmers from Tak province, and foragers from Phatthalung province. Our results reveal that microbiomes of all populations are primarily dominated by the families Prevotellaceae, Bacteroidaceae, and Lachnospiraceae, yet their specific abundances differ between populations. -diversity, particularly Faiths phylogenetic diversity, showed a descending trend from the rural to urban populations. Despite these differences, results suggested that most highly prevalent microbial genera were shared among all groups, suggesting the existence of a consistent core microbiome within the Thai population, despite differing lifestyles. Further, association analysis shows that overall population-wide lifestyle was significantly associated with microbial community structure, explaining 0.5-4% of the variation depending on the {beta}-diversity metrics. Linking dietary habits and other lifestyle factors to genus abundance revealed population-specific microbiome-lifestyle associations, indicating that baseline microbial community composition determines microbiome variability in response to environmental changes. Overall, our study expands the scope of lifestyle-microbiome research and identifies associations between lifestyle and microbial features, underscoring the influence of lifestyle factors and baseline microbiomes on microbial compositional adaptation.

microbiology↗

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 a multi-level deregulation of host-microbiome metabolic networks in IBD

Inflammatory bowel diseases (IBDs) are chronic disorders involving dysregulated immune responses. Despite the role of disrupted host-microbial interaction in the pathophysiology of IBD, the underlying metabolic principles are not fully understood. We densely profiled microbiome, transcriptome and metabolome signatures from longitudinal IBD cohorts before and after advanced drug therapy initiation and reconstructed metabolic models of the gut microbiome and the host intestine to study host-microbiome metabolic cross-talk in the context of inflammation. We identified concomitant changes in metabolic activity across data layers involving NAD, amino acid, one-carbon and phospholipid metabolism. In particular on the host level, elevated tryptophan catabolism depleted circulating tryptophan, thereby impairing NAD biosynthesis. Reduced host transamination reactions disrupted nitrogen homeostasis and polyamine/glutathione metabolism. The suppressed one-carbon cycle in patient tissues altered phospholipid profiles due to limited choline availability. Simultaneously, microbiome metabolic shifts in NAD, amino acid and polyamine metabolism exacerbated these host metabolic imbalances. Leveraging host and microbe metabolic models, we predicted dietary interventions remodeling the microbiome to restore metabolic homeostasis, suggesting novel therapeutic strategies for IBD.

systems biology↗

bioRxiv2024

Virtual Colon: Spatiotemporal modelling of metabolic interactions in a computational colonic environment

1.Host-microbial metabolic interactions have been recognised as an essential factor in host health and disease. Genome-scale metabolic modelling approaches have made important contributions to our understanding of the interactions in such communities. One particular such modelling approach is BacArena in which metabolic models grow, reproduce, and interact as independent agents in a spatiotemporal metabolic environment. Here, we present a modelling application of BacArena, a virtual colonic environment, which reveals spatiotemporal metabolic interactions in a computational colonic environment. This environment resembles the crypt space together with the mucus layers, the lumen and fluid dynamics. Our proof-of-principle experiments include mono-colonisation simulations of context-specific colonic cells and simulations of context-specific colonic cells with the SIHUMIx minimal model microbiome. Our simulations propose host-microbial and microbial-microbial interactions that can be verified based on the literature. Most importantly, the Virtual Colon offers visualisation of interactions through time and space, adding another dimension to the genome-scale metabolic modelling approaches. Lastly, like BacArena, it is freely available and can be easily adapted to model other spatially structured environments (http://www.github.com/maringos/VirtualColon).

systems biology↗

bioRxiv2024

Epithelial Hexokinase 2 expression is a marker for intestinal inflammation

BackgroundInflammation is characterized by a metabolic switch promoting glycolysis and lactate production. Hexokinases (HK) catalyze the first reaction of glycolysis and inhibition of epithelial HK2 protected from colitis in mice. HK2 expression has been described as elevated in patients with intestinal inflammation, however there is conflicting data from few cohorts especially with severely inflamed individuals, thus systematic studies linking disease activity with HK2 levels are needed. MethodsWe examined the relationship between HK2 expression and inflammation severity using bulk transcriptome data derived from the mucosa of thoroughly phenotyped patients suffering from intestinal inflammation of two independent cohorts. Analyzing publicly available single cell RNA sequencing data and performing immunofluorescence on colonic biopsies of unrelated patients with intestinal inflammation confirmed the RNA-based findings on cellular and protein level. ResultsHK2 expression gradually increased from mild to intermediate inflammation, yet strongly declined at high inflammation scores. Expression of epithelial marker genes also declined at high inflammation scores, whereas that of candidate immune marker genes increased, indicating a cellular remodeling of the mucosa during inflammation with an infiltration of HK2-negative immune cells and a loss of the apical epithelium - the main site of HK2 expression. Normalizing for the enterocyte loss clearly identified epithelial HK2 expression as gradually increasing with disease activity and remaining elevated at high inflammation scores. HK2 protein expression was mostly restricted to brush border enterocytes and these cells along with HK2 levels vanished with increasing disease severity. ConclusionsOur findings clearly define dysregulated epithelial HK2 expression as an indicator of disease activity in intestinal inflammation and suggest targeted HK2-inhibition as a potential therapeutic avenue.

immunology↗

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↗

bioRxiv2023

Evolution of E. coli in a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance

Inflammatory bowel disease (IBD) is a persistent inflammatory condition that affects the gastrointestinal tract and presents significant challenges in its management and treatment. Despite the knowledge that within-host bacterial evolution occurs in the intestine, the disease has rarely been studied from an evolutionary perspective. In this study, we aimed to investigate the evolution of resident bacteria during intestinal inflammation and whether- and how disease-related bacterial genetic changes may present trade-offs with potential therapeutic importance. Here, we perform an in vivo evolution experiment of E. coli in a gnotobiotic mouse model of IBD, followed by multiomic analyses to identify disease-specific genetic and phenotypic changes in bacteria that evolved in an inflamed versus a non-inflamed control environment. Our results demonstrate distinct evolutionary changes in E. coli specific to inflammation, including a single nucleotide variant that independently reached high frequency in all inflamed mice. Using ex vivo fitness assays, we find that these changes are associated with a higher fitness in an inflamed environment compared to isolates derived from non-inflamed mice. Further, using large-scale phenotypic assays, we show that bacterial adaptation to inflammation results in clinically relevant phenotypes, which intriguingly include collateral sensitivity to antibiotics. Bacterial evolution in an inflamed gut yields specific genetic and phenotypic signatures. These results may serve as a basis for developing novel evolution-informed treatment approaches for patients with intestinal inflammation.

evolutionary biology↗

bioRxiv2023

Metabolic model predictions enable targeted microbiome manipulation through precision prebiotics

1.The microbiome is increasingly receiving attention as an important modulator of host health and disease. However, while numerous mechanisms through which the microbiome influences its host have been identified, there is still a lack of approaches that allow to specifically modulate the abundance of individual microbes or microbial functions of interest. Moreover, current approaches for microbiome manipulation such as fecal transfers often entail a non-specific transfer of entire microbial communities with potentially unwanted side effects. To overcome this limitation, we here propose the concept of precision prebiotics that specifically modulate the abundance of a microbiome member species of interest. In a first step, we show that defining precision prebiotics by compounds that are only taken up by the target species but no other species in a community is usually not possible due to overlapping metabolic niches. Subsequently, we present a metabolic modeling network framework that allows us to define precision prebiotics for a two-member C. elegans microbiome model community comprising the immune-protective Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71. Thus, we predicted compounds that specifically boost the abundance of the host-beneficial MYb11, four of which were experimentally validated in vitro (L-serine, L-threonine, D-mannitol, and {gamma}-aminobutyric acid). L-serine was further assessed in vivo, leading to an increase in MYb11 abundance also in the worm host. Overall, our findings demonstrate that constraint-based metabolic modeling is an effective tool for the design of precision prebiotics as an important cornerstone for future microbiome-targeted therapies.

systems biology↗

bioRxiv2022

Bacterial colonizers of Nematostella vectensis are initially selected by the host before interactions between bacteria determine further succession

The microbiota of multicellular organisms undergoes considerable changes during development but the general mechanisms that control community assembly and succession are poorly understood. Here, we use bacterial recolonization experiments in Nematostella vectensis as a model to understand general mechanisms determining bacterial establishment and succession. We compared the dynamic establishment of the microbiome on the germfree host and on inert silica. Following the dynamic reconstruction of microbial communities on both substrates, we show that the initial colonization events are strongly influenced by the host but not by the tube, while the subsequent bacteria-bacteria interactions are the main cause of bacterial succession. Interestingly, the recolonization pattern on adult hosts resembles the ontogenetic colonization succession. This process occurs independently of the bacterial composition of the inoculum and can be followed at the level of individual bacteria, suggesting that priority effects are neglectable for early colonization events in Nematostella. To identify potential metabolic traits associated with initial colonization success and potential metabolic interactions among bacteria associated with bacterial succession, we reconstructed the metabolic networks of bacterial colonizers based on their genomes. These analyses revealed that bacterial metabolic capabilities reflect the recolonization pattern, and the degradation of chitin might be a selection factor during early colonization of the animal. Concurrently, transcriptomic analyses revealed that Nematostella possesses two chitin synthase genes, one of which is upregulated during early recolonization. Our results show that early colonization events are strongly controlled by the host while subsequent colonization depends on metabolic bacteria-bacteria interactions largely independent of host development.

microbiology↗

bioRxiv2019

Bacteria- and temperature-regulated peptides modulate beta-catenin signaling in Hydra

Animal development has traditionally been viewed as an autonomous process directed by the host genome. But in many animals biotic and abiotic cues, like temperature and bacterial colonizers, provide signals for multiple developmental steps. Hydra offers unique features to encode these complex interactions of developmental processes with biotic and abiotic factors. Here, we used the model animal Hydra to investigate the impact of bacterial colonizers and temperature on the pattern formation process. In Hydra, formation of the head organizer involves the canonical Wnt pathway. Treatment with alsterpaullone (ALP) results in acquiring characteristics of the head organizer in the body column. Intriguingly, germ-free Hydra polyps are significantly more sensitive to ALP compared to control polyps. In addition to microbes, {beta}-catenin dependent pattern formation is also affected by temperature. Gene expression analyses led to the identification of two small secreted peptides, named Eco1 and Eco2, being upregulated in the response to both, Curvibacter sp, the main bacterial colonizer of Hydra, and low temperatures. Loss-of function experiments revealed that Eco peptides are involved in the regulation of pattern formation and have an antagonistic function to Wnt signaling in Hydra.

developmental biology↗