Biology subjects

Kaleta, C.

Publications and source records attributed to Kaleta, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Expression trajectories in the aging male mouse colon transcriptome

Characterizing temporal dynamics during aging is crucial to understanding the course of aging-related events. The transcriptome is extensively remodeled with age, but the temporal trajectories of these changes, particularly through midlife, remain poorly defined in many tissues. Here, we address this gap in the male mouse colon. Using a dataset of 83 RNA-Seq samples from five time points during adult mouse lifespan, we show that colon aging is characterized by multiple gene-expression trajectories unfolding in parallel, with a major shift occurring during a mid- to late-life transition marked by a collapse of the unfolded protein response (UPR). Moreover, we report widespread non-monotonic trajectories, including genes that peak or dip in midlife and would be missed by comparisons limited to young versus old ages. We further describe age-dependent dynamics of transposable element-containing transcripts and a nonlinear course of transcriptomic entropy across the lifespan. Importantly, we identify a small set of genes that track chronological age and use only three of them to construct a compact transcriptomic clock, which we validate using an independent RNA-seq dataset and qPCR data. Together, our results indicate that nonlinear patterns dominate the aging colon transcriptome and underscore the value of high temporal resolution for identifying key transitions during aging.

bioinformatics↗

bioRxiv2026

Coculture of Collinsella aerofaciens and Bacteroides thetaiotaomicron under bile acid stress reveals vitamin B6 exchange

Although bile acid-mediated microbiome-host interactions are known to shape gut microbial composition and function, the mechanisms by which bile acid stress influences microbial metabolic interactions remain poorly understood. Here, we investigated the interaction between two key gut microbes, Bacteroides thetaiotaomicron and Collinsella aerofaciens, under deoxycholic acid (DCA) stress. In anaerobic coculture, C. aerofaciens mitigated the inhibitory effects of DCA on B. thetaiotaomicron, primarily through DCA uptake from the medium, as confirmed by DCA quantification. Proteomic analysis showed that DCA broadly disrupted amino acid and vitamin metabolism, particularly in B. thetaiotaomicron. In contrast, coculture promoted widespread metabolic activation in C. aerofaciens, including enhanced vitamin B6 metabolism and increased production of citrulline and ornithine. These findings suggest that metabolic cooperation enhances resistance to bile acid stress and may contribute to gut microbiome resilience, with potential relevance to liver- and bile acid-related disorders.

microbiology↗

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

Context-Dependent Metabolic Adaptation in Microbial Communities: From Monocultures to Complex Ecological Interactions

Microbial communities perform myriad functions in various environments, including the mammalian gut. These functions are largely based on the metabolic activity of microbial communities, which arises from the individual members contributions and their interactions. However, microbial functions and interactions are often inferred from simplified systems such as pure or pairwise cultures. Larger communities, in particular, are mainly analysed by metagenomics and the activity is deduced from the genetic potential of their community members. Although these approaches allow detailed insights into compositions, pairwise interactions and potential functions, they neglect the complexities of microbial communities, as evident in higher-order relationships, competition outcomes and the regulatory influence of environmental factors and other community members. Here, we study a mouse gut community along a gradient of complexity - from monocultures, to in vitro communities, to the mouse gut, to probe how bacteria adapt metabolically to their biotic and abiotic environments. Using metaproteomics to analyze realized bacterial niches and metabolic modeling to infer community interactions, we found that bacteria substantially modify their carbon source usage, biosynthetic activities, and protein allocation when grown in communities versus isolation. Furthermore, communities themselves adapted to their growth environment, changing in functionality as well as in the metabolic network between members. Host-associated communities isolated from the mouse gut invested in resource acquisition and utilized a broader spectrum of carbon sources, resulting in a large increase of predicted interactions between them. Our findings demonstrate the remarkable adaptability of microbes and microbial communities across environmental contexts. This underscores the critical need to study microbiomes under near-natural conditions and incorporate context-specific data into functional analyses.

systems biology↗

bioRxiv2025

Genome-scale metabolic models predict diet- and lifestyle-driven shifts of ecological interactions in the gut microbiome

1.Microbiomes and their host environments form complex, interconnected ecosystems. The microbial species within a microbiome, on the one hand, compete for resources, while on the other hand, they exchange vital metabolites to support their survival. These interactions are influenced by the microbial genetic repertoire, environmental conditions, and the availability of nutrients. We developed EcoGS (http://www.github.com/KaletaLab/EcoGS), a metabolic modelling tool designed to predict ecological interactions between pairs of microbes. Applying EcoGS to the microbiomes of two distinct human cohorts revealed a shift from collaborative to exploitative ecological interactions associated with higher dietary intake of simple sugars (glucose and fructose), in diabetic individuals and those living in industrialised lifestyles. On the other hand, the consumption of Cobalamin (vitamin B12), phylloquinone (vitamin K1) and biotin (vitamin B7), among other compounds, was associated with increased collaboration in the gut microbiome. We conclude that the abundance of simple sugars as an energy source reduces the necessity for microbes to cooperate, thereby increasing competition and hostility among microbiome members. Moreover, our study proposes multiple compounds, such as urate, deoxyadenosine, deoxyguanosine, and hypoxanthine, for in vitro validation tests as dietary interventions that have the potential to restore the ecological balance amongst the community. EcoGS serves as a valuable tool for exploring microbiome dynamics and their connections to environmental changes and disease.

systems biology↗

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

Deletion of epithelial HKDC1 decelerates cellular proliferation and impairs mitochondrial function of tumorous epithelial cells thereby protecting from intestinal carcinogenesis in mice

BackgroundA metabolic switch favoring glycolysis over aerobic oxidative phosphorylation, namely the "Warburg effect", represents a hallmark of cancer cells. Hexokinases (HK) catalyze the first step of glycolysis, thereby regulating its rate. Dysregulated HKDC1 (HK domain containing 1) expression has been associated with various cancer types and blocking HKDC1 prevents disease progression for hepatic carcinoma T cell lymphoma and lung adenocarcinoma, but its implication for colorectal cancer (CRC) remained unknown. Here, we functionally investigated the role of HKDC1 for intestinal carcinogenesis. MethodsFirst, we analyzed HKDC1 expression in the intestinal mucosa of healthy controls (HC) and CRC patients and in different tumor tissues using transcriptomic data from publicly available databases. We then generated HKDC1-deficient human and murine colonic epithelial cell lines as well as intestinal organoids and profiled their phenotypic functions. Next, we screened for proteins interacting with HKDC1 by immunoprecipitation. Finally, we generated tumor-bearing ApcMin/+ mice with a conditional deletion of HKDC1 in intestinal epithelial cells and also performed a xenograft mouse model to test the role of HKDC1 for intestinal carcinogenesis in vivo. ResultsHKDC1 was found to be overexpressed in tumor compared to normal tissue of CRC patients. In vitro, HKDC1-deficient human Caco-2 and murine CMT-93 cells displayed reduced proliferation, altered susceptibility to cell death induction, and disrupted mitochondrial functions, particularly mitochondrial respiration. These altered cancer hallmarks were then corroborated in HKDC1-deficient normal and tumor-derived ApcMin/+ intestinal organoids. Immunoprecipitation and mass spectometry proteomic analyses revealed interactions of HKDC1 with several mitochondria-related proteins. In vivo, two distinct mouse models demonstrated that epithelial deletion of HKDC1 protected from carcinogenesis. First, ApcMin/+-Hkdc1{Delta}IEC mice showed mildly improved disease phenotypes in the colon accompanied with reduced numbers of Ki67-positive proliferating epithelial cells. Finally, HKDC1-deficient Caco-2 cells completely failed to form any tumor mass in a xenograft model when implanted into immunodeficient mice. ConclusionsWe demonstrate that HKDC1 influences cancer cell proliferation and susceptibility to cell death, potentially through interactions with mitochondrial proteins that regulate membrane permeability, ultimately impacting intestinal carcinogenesis. Collectively, these findings highlight the significance of HKDC1 for CRC pathobiology, presenting it as a promising target for further investigation and potential therapeutic interventions.

cancer 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

Metabolic modelling reveals increased autonomy and antagonism in type 2 diabetic gut microbiota

1.Type 2 diabetes presents a growing global health concern, with emerging evidence highlighting the pivotal role of the human gut microbiome in metabolic diseases. This study employs metabolic modelling to elucidate changes in host-microbiome interactions in type 2 diabetes. Glucose levels, dietary intake, 16S sequences and metadata were estimated and collected for a cohort of 1,866 individuals. In addition, microbial community models, as well as ecological interactions were simulated for the gut microbiomes of the cohort participants. Our findings revealed a significant decrease in the fluxes of metabolites provided by the host to the microbiome through the diet in patients with type 2 diabetes, accompanied by an increase in within-community exchanges. Moreover, the diabetic microbial community shifts towards increased exploitative ecological interactions among its member species at the expense of collaborative interactions. The reduced butyrate flux from the community to the host and reduced tryptophan acquired by the microbiome from the hosts diet further highlight the dysregulation in microbial-host interactions in diabetes. Additionally, microbiomes of type 2 diabetes patients exhibit enrichment in energy metabolism pathways, indicative of increased metabolic activity and antagonism. This study provides insights into the metabolic dynamics of the diabetic gut microbiome, shedding light on its increased autonomy and altered ecological interactions accompanying diabetes, and provides candidate metabolic targets for intervention studies and experimental validations, such as butyrate, tryptophan, H2S, several nucleotides, amino acids, and B vitamins.

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↗

bioRxiv2024

Metatranscriptomics-based metabolic modeling of patient-specific urinary microbiome during infection

Urinary tract infections (UTIs) are a major health concern which incur significant socioeconomic costs in addition to substantial antibiotic prescriptions, thereby accelerating the emergence of antibiotic resistance. To address the challenge of antibiotic-resistant UTIs, our systems biology approach uncovers patient-specific uromicrobiome insights that are focused on community utilization of metabolites. By leveraging the distinct metabolic traits of patient-specific pathogens, we aim to identify metabolic dependencies of pathogens and provide suggestions for targeted interventions for future studies. Combining patient-specific metatranscriptomic data with genome-scale metabolic modeling and data from the Human Urine Metabolome, this study explores UTIs from a systems biology perspective through the reconstruction of tailored microbial community models to mirror the metabolic profiles of individual UTI patients urinary microbiomes. Delving into patient-specific bacterial gene expressions and microbial interactions, we identify metabolic signatures and propose mechanisms for UTI pathology. Our research underscores the potential of integrating metatranscriptomic data using systems biological approaches, providing insights into disease metabolic mechanisms and potential phenotypic manifestations. This contribution introduces a new method that could guide treatment options for antibiotic-resistant UTIs, aiming to lessen antibiotic use by combining the pathogens unique metabolic traits. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/586446v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1074251org.highwire.dtl.DTLVardef@192d45eorg.highwire.dtl.DTLVardef@b46927org.highwire.dtl.DTLVardef@638e2a_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract Metatranscriptome sequencing was used to investigate the functional uromicrobiome across a cohort of 19 individuals; patient-specific microbiome community models were reconstructed and simulated in a virtual urine environment. Total RNA was extracted from patients urine and sequenced to assess the metatranscriptome, providing insights into patient-specific uromicrobiome microbial taxa and their associated gene expression during urinary tract infections (UTIs). These combinatory datasets derived from metatranscriptomics data were further expanded first to reconstruct species specific metabolic models that were conditioned with gene expression. Gene expression conditioned metabolic models were combined in an in silico environment with a defined urine media to construct patient-specific context-specific uromicrobiome models, enabling an understanding of each patients unique microbiome. Using this approach, we aimed to identify patient-specific microbiome dynamics and provide insight towards various metabolic features that can be utilized or validated in future studies for individualized intervention strategies. Created with www.biorender.com. C_FIG

systems biology↗

bioRxiv2024

Polyketide synthase-derived sphingolipids determine microbiota-mediated protection against pathogens in C. elegans

Protection against pathogens is a major function of the gut microbiota. Although bacterial natural products have emerged as crucial components of host-microbiota interactions, their exact role in microbiota-mediated protection is largely unexplored. We addressed this knowledge gap with the nematode Caenorhabditis elegans and its microbiota isolate Pseudomonas fluorescens MYb115 that is known to protect against Bacillus thuringiensis (Bt) infection. We find that MYb115-mediated protection depends on sphingolipids that are derived from an iterative type I polyketide synthase (PKS), thereby describing a noncanonical pathway of bacterial sphingolipid production. We provide evidence that MYb115-derived sphingolipids affect C. elegans tolerance to Bt infection by altering host sphingolipid metabolism. This work establishes sphingolipids as structural outputs of bacterial PKS and highlights the role of microbiota-derived sphingolipids in host protection against pathogens.

molecular 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

Gut-associated functions are favored during microbiome assembly across C. elegans life

The microbiome expresses a variety of functions that influence host biology. The range of functions depends on composition of the microbiome, which itself can change during the lifetime of the host as a consequence of neutral assembly processes, host-mediated selection, and/or environmental conditions. To date, the exact dynamics of microbiome assembly, the underlying determinants as well as the resulting effects on host-associated functions are not always well understood. Here, we used the nematode Caenorhabditis elegans and a defined community of fully sequenced, naturally associated bacteria to study microbiome dynamics and functions across the lifetime of individual hosts under controlled experimental conditions. By applying the neutral and null models, we demonstrate that bacterial community composition initially shows strongly declining levels of stochasticity, which, however, increase during late worm life, suggesting the action of random assembly processes in aged hosts following first colonization of C. elegans. The adult microbiome is enriched in strains of the genera Ochrobactrum and Enterobacter in comparison to the direct substrate and a host-free control environment. Using pathway analysis, metabolic, and ecological modelling, we further found that the lifetime assembly dynamics lead to an increase in gut-associated functions in the host-associated microbiome, possibly indicating that the initially colonizing bacteria are beneficial for the worm. Overall, our study introduces a framework for studying microbiome assembly dynamics based on the stochastic models and inference of functions, yielding new insights into the processes determining host-associated microbiome composition and function. ImportanceThe microbiome plays a crucial role in host biology, with its functions depending on microbiome composition that can change during a hosts lifetime. To date, the dynamics of microbiome assembly and the resulting functions are not well understood. This study introduces a new approach to characterize the functional consequences of microbiome assembly by modelling both, the relevance of stochastic processes and metabolic characteristics of microbial community changes. The approach was applied to experimental time series data, obtained for the microbiome of the nematode Caenorhabditis elegans. The results revealed significant differences in host-associated and environmental microbiomes. Stochastic processes only played a minor role, and the host showed an increase in beneficial bacteria and an enrichment of gut-associated functions, possibly indicating that the host actively shapes composition of its microbiome. Overall, this study provides a framework for studying microbiome assembly dynamics and yields new insights into C. elegans microbiome functions.

evolutionary biology↗

bioRxiv2023

Closely related Bacteroides of the murine intestinal microbiota affect each other's growth positively or negatively

The mammalian intestine is a unique ecosystem for thousands of bacterial species and strains. How naturally coexisting bacteria of the microbiota interact with each other is not yet fully understood. Here, we isolated formerly coexisting, closely related strains of the genus Bacteroides from the intestines of healthy, wild-derived mice. The effect of one strain on another strains growth was tested in 169 pairs in vitro. We find a vast diversity of growth promoting and growth inhibiting activities. A strong positive effect was observed between two strains with differing metabolisms. Growth inhibition among a subset of strains was associated with the known bacterial toxin bacteroidetocin B. Across all strains, we observed growth promotion more often than growth inhibition. The effects were independent of two strains belonging to the same or different species. In some cases, one species differed in its effect on another according to host origin. These findings on obligate host-associated bacteria demonstrate that closely related and naturally coexisting strains have the potential to affect each others growth positively or negatively. These results have implications for our basic understanding of host-associated microbes and the design of synthetic microbial communities.

microbiology↗