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Schulenburg, H.

Publications and source records attributed to Schulenburg, H..

At least 19 recordsLinked to original sources

Microbially Assisted Rescue of Host Populations

Rapid environmental change can drive populations into decline but host genomes may adapt in time to rescue the population from extinction. Host-associated microbes may alter this race. We here develop a population-genetics model to characterize the dynamics and consequences of microbe-assisted host population rescue. In our model, we replace one locus of a classical two-locus system with microbial carriage. Under weak selection the microbial variables settle to a quasi-microbial equilibrium (QME) conditional on the host allele, reducing the coupled dynamics to host allele frequency and abundance. The reduction identifies two microbial contributions that shape rescue. Additive benefits of microbial carriage on host fitness raise host growth immediately without affecting evolution and lift the floor of the demographic rescue-U. By contrast, positive interactions between the rescue allele and the microbe accelerate evolution and narrow the rescue-U instead of buffering initial decline. A microbe can therefore buy time, speed adaptation, or be required for recovery when neither contribution suffices alone. Imperfect microbial inheritance, however, can impede microbe-assisted rescue. When selection acts through fecundity and carriers transmit the microbe to only some offspring, adaptation generates non-carrying descendants faster than transmission replaces them. When that loss is sufficiently strong, recovery can fail even though the allele, the microbe, and their interaction are each individually beneficial. We call this selection-amplified dilution. Together, our model integrates evolutionary rescue theory with multilocus population genetics and evolutionary epidemiology to define a framework of microbe-assisted host rescue, thereby identifying key factors driving or compromising the rescue process.

evolutionary biology↗

Evolutionary trade-offs between antimicrobial resistance and virulence in Pseudomonas aeruginosa

Antibiotics impose strong selection on bacteria, resulting in the emergence and spread of antimicrobial resistance. To date, the consequences of resistance evolution for other traits, especially virulence as a key life-history characteristic of high medical relevance remain poorly understood. A central limitation of existing work is reliance on clinical isolates with complex evolutionary histories, hindering causal inferences on resistance-virulence relationships. Such causal information is critical for our understanding of the distribution of resistance-associated evolutionary trade-offs, which may additionally guide optimization of treatment designs. The objectives of our study are to address these knowledge gaps using an experimental evolution framework with the human pathogen Pseudomonas aeruginosa. We quantified changes in resistance, life-history characteristics, in-vivo virulence with a Caenorhabditis elegans infection model, and whole genome sequences for bacterial clones, which had been independently evolved under three antibiotics with distinct cellular targets. We found that the resistance-virulence trade-off depended on the used antibiotic and was additionally driven by the underlying evolutionary path to resistance. Evolved resistance to the fluoroquinolone ciprofloxacin correlated positively with virulence, dependent on genetic changes in either the antibiotic target or efflux regulation. Conversely, evolved resistance to piperacillin/tazobactam, a {beta}-lactam/{beta}-lactamase inhibitor combination, was negatively correlated with virulence, contingent on the coincidental spread of resistance mutations and a large genomic deletion, containing numerous virulence genes. Lastly, evolved resistance to the aminoglycoside streptomycin led to only minor virulence changes. Overall, these antibiotic-specific evolutionary trajectories challenge the assumption of a universal resistance-virulence trade-off and demonstrate that antibiotic choice itself shapes pathogen virulence potential. Significance StatementAntimicrobial resistance and bacterial virulence are typically studied in isolation, yet they are shaped by the same evolutionary pressures and may directly compete for cellular resources. We addressed a fundamental but unresolved question: does evolution of resistance to an antibiotic make a pathogen more or less dangerous to a host? By characterizing experimentally evolved Pseudomonas aeruginosa, a leading cause of drug-resistant infections, we show that the answer depends on which antibiotic drove resistance. A positive resistance-virulence relationship occurred upon adaptation to a fluoroquinolone antibiotic, whereas it was negative upon {beta}-lactam resistance, and unchanged upon aminoglycoside resistance evolution. These antibiotic-specific evolutionary trajectories challenge the assumption of a universal resistance-virulence trade-off and suggest that antibiotic choice shapes pathogen danger beyond drug susceptibility.

evolutionary biology↗

Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope

Antibiotic combination in time and space is a key strategy to combat antimicrobial resistance. The success of such treatment designs requires their robust efficacy across treatment conditions and a pathogens genomic diversity. This study found that an initial treatment with a {beta}-lactam antibiotic causes robust cellular sensitization towards an aminoglycoside antibiotic across the high-risk human pathogen Pseudomonas aeruginosa, including resistant strains. This phenomenon of cellular sensitization, termed negative hysteresis, is modulated by the Cpx envelope stress response system and linked to membrane stress during growth. The increase in efficacy is achieved through a {beta}-lactam induced elevated cellular uptake of the subsequently administered aminoglycoside. Negative hysteresis and the Cpx system are linked in several cases to the expression of synergistic drug interactions, thus enhancing efficacy of antibiotic combinations. Overall, our study identifies the phenomenon of negative hysteresis as a robustly inducible phenotype and thus a unique focus for optimizing antimicrobial therapy.

evolutionary biology↗

Evolution of β-lactam resistance causes fitness reductions and several cases of collateral sensitivities in the human pathogen Haemophilus influenzae

The evolution of antimicrobial resistant (AMR) pathogens poses a global health threat and it is unclear if evolutionary trajectories to resistance lead to predictable phenotypes. We analyzed AMR-evolution in the human pathogen Haemophilus influenzae in controlled evolution experiments with increasing concentrations of either ampicillin, cefotaxime, or ceftriaxone. We isolated 315 clones from different time points of six independent experiments and characterized changes in genome sequences, bacterial fitness, and minimum inhibitory concentrations (MICs) to 14 antibiotics. Resistance evolution under ampicillin and cefotaxime was mainly driven by mutations in the ftsI gene, encoding the penicillin-binding protein 3. However, ceftriaxone exposure repeatedly selected for amino acid substitutions in the outer membrane protein P2 (OmpP2). Some OmpP2-mutants reproducibly showed phenotypic heterogeneity for ceftriaxone but also for fluoroquinolones, rifampicin and tetracycline. Bacterial fitness assessments revealed trade-offs between resistance-associated mutations and growth, though no systematic correlation of MIC increase and growth deficit was detected. Over 50% of the selected clones became more susceptible to aminoglycosides, clarithromycin, and colistin, while some mutation patterns resulted in cross-resistance to meropenem and fluoroquinolones. Overall, beta-lactam antibiotics reproducibly selected mutants with increased MICs, but evolutionary pathways and resulting phenotypes remain unpredictable. These findings highlight the complexity of resistance evolution and suggest that future AMR treatment strategies may need to consider strain-specific and collateral effects more closely.

genomics↗

Resistance variation and bacterial interactions shape the adaptation of a genetically diverse bacterial population to antimicrobial treatment

Bacterial infections are often polymicrobial and subject to the evolution of antimicrobial resistance (AMR). Existing knowledge on AMR in such polymicrobial infections usually relies on observational patient data, for which cause-effect relationships are difficult to infer, or on studying interactions between different bacterial species, ignoring the commonly encountered variation within species. Here, we therefore asked how mixed populations with strains from the same species evolve under antibiotic treatment. We used a genetically diverse population of the high-risk human pathogen Pseudomonas aeruginosa, and first identified strain variation in both AMR and pairwise bacteria-bacteria interactions, the latter ranging from beneficial, neutral, to competitive. Using experimental evolution, we subsequently demonstrate that the response to selection by different antibiotic treatments is significantly influenced by AMR strain variation, bacterial interactions, and also spatial population structure. Moreover, de novo AMR evolution was additionally impacted by variation in resistance rates towards the two considered antibiotics. A second evolution experiment emphasized the central role of strain variation and bacterial interactions in determining the evolutionary outcome. We conclude that ecological dynamics in genetically diverse pathogen populations are key for our general understanding of infection characteristics and AMR evolution, and, therefore, deserve particular attention during treatment of polymicrobial infections.

evolutionary biology↗

The nematode Caenorhabditis elegans can benefit from its coexisting fungal microbiome member Barnettozyma californica

The nematode Caenorhabditis elegans is known to feed on and interact with bacteria in its environment and has become a model organism for microbiome studies. However, whether and how C. elegans interacts with co-occurring fungi remains largely unknown, despite the presence of many fungal species in its natural habitat. Here, we isolate the yeast Barnettozyma californica from a mesocosm experiment with C. elegans and characterize its genome and interaction with the nematode. We find that B. californica is ingested by C. elegans and can serve as a sole, albeit poor, food source. Yet, when present together with Escherichia coli OP50, the fungus can lead to higher population growth and altered foraging behavior, suggesting that this fungi-bacteria mixture provides a better food source than bacteria alone. This effect varied between different natural C. elegans strains, suggesting a genomic basis for the nematodes interaction with B. californica. The fully assembled and annotated genome of the isolated B. californica strain does not indicate any obvious candidate genes for its interaction with C. elegans and/or E. coli OP50. Overall, our results provide an intriguing example of the complexity and multi-level relationship between naturally interacting fungi, bacteria, and animals. Graphical AbstractBarnettozyma californica is a member of the fungal microbiome of the model nematode Caenorhabditis elegans and can serve as food for worms. When combined with E. coli, this fungus can increase population growth and reduce foraging behaviour dependent on C. elegans genotype, revealing a genetic influence on host-fungus-bacterium interactions. O_FIG O_LINKSMALLFIG WIDTH=189 HEIGHT=200 SRC="FIGDIR/small/638710v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@184b29eorg.highwire.dtl.DTLVardef@eabb71org.highwire.dtl.DTLVardef@b810ceorg.highwire.dtl.DTLVardef@5745c7_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

Comparative analysis of novel Pseudobdellovibrionaceae genera and species yields insights into the genomics and evolution of bacterial predation mode

Bacteria of the family Pseudobdellovibrionaceae belong to a group of bacteria that kill and feed on other bacteria. The diversity of predation strategies, habitats, and genome characteristics of these bacteria are largely unexplored, despite their ecological and evolutionary importance in microbial communities. Therefore, we characterized new Pseudobdellovibrionaceae strains isolated from the direct environments of three animal hosts: the zebrafish (Danio rerio), the threespine stickleback fish (Gasterosteus aculeatus), and the nematode Caenorhabditis elegans. We used transmission electron microscopy (TEM) and genomic analyses to characterize the morphology and predation modes of our isolates. While most of our isolates exhibited periplasmic (i.e. endoparasitic) predation, one isolate clearly exhibited epibiotic (i.e. exoparasitic) predation and represents only the third confirmed epibiotic strain within its clade. Of our isolates, six are members of five new species in the genus Bdellovibrio and two strains likely represent new genera within the family Pseudobdellovibrionaceae. From metabarcoding data, we found indications that Pseudobdellovibrionaceae are widespread among our three animal hosts. Genomic analyses showed that epibiotic predators lack genes involved in host independence (i.e. prey-independent feeding) and peptidoglycan modification. However, genes unique to epibiotic predators may underlie this predation mode, particularly those involved in cell wall remodeling and recycling. With robust phylogenomic analyses, we show that our novel isolates cluster with previously described Pseudobdellovibrionaceae isolates according to predation mode. Further, by placing Pseudobdellovibrionaceae predators within a wider evolutionary history including other predatory and non-predatory bacteria, we postulate periplasmic predation as the ancestral mode, with more derived epibiotic predators exhibiting genome streamlining.

genomics↗

Evolution of ivermectin resistance in the nematode model Caenorhabditis elegans: critical influence of population size and unexpected cross-resistance to emodepside

The emergence and spread of anthelmintic resistance represent a major challenge for treating parasitic nematodes, threatening mass-drug control programs in humans and zoonotic species. Currently, experimental evidence to understand the influence of management (e.g., treatment intensity and frequency) and parasite-associated factors (e.g., genetic variation, population size and mutation rates) is lacking. To rectify this knowledge gap, we performed controlled evolution experiments with the model nematode Caenorhabditis elegans and further evaluated the evolution dynamics with a computational model. Large population size was critical for rapid ivermectin resistance evolution in vitro and in silico. Male nematodes were favored during resistance evolution, indicating a selective advantage of sexual recombination under drug pressure in vitro. Ivermectin resistance evolution led to the expected emergence of cross-resistance to the structurally related anthelmintic moxidectin but unexpectedly also to the structurally unrelated anthelmintic emodepside that has an entirely different mode of action. In contrast, albendazole, levamisole, and monepantel efficacy were not influenced by the evolution of Ivermectin resistance. We conclude that combining computational modeling with in vitro evolution experiments to test specific aspects of evolution directly represents a promising approach to guide the development of novel treatment strategies to anticipate and mitigate resistance evolution in parasitic nematodes.

evolutionary biology↗

Investigating the consequences of the mating system for drug resistance evolution in C. elegans

The rise of anthelmintic-resistant strains in livestock threatens both animal and human health. Understanding the factors influencing anthelmintic resistance is crucial to mitigate the threat posed by these parasites. Due to difficulties in studying parasitic worms in the laboratory, the non-parasitic nematode Caenorhabditis elegans is used as a model organism to investigate anthelmintic resistance evolution. However, the suitability of this free-living nematode as a model for parasitic worms is debatable due to its rare androdioecious reproductive system, raising questions about the generalizability of findings from evolutionary experiments in C. elegans to other species. In this study, we developed a polygenic, population genetic model combined with pharmacodynamic approaches to investigate the effects of reproductive strategy and other aspects, such as dominance, mutational effects, the number of loci, and population size, on determining the dynamics and outcome of evolutionary processes. We found that androdioecious populations showed both rapid initial adaptation typical for hermaphrodites and tolerance to high drug concentrations observed in dioecious populations. They also exhibited the highest diversity and shortest time for the fixation of the beneficial allele. These results suggest that androdioecious populations can harness the advantages of both selfing and outcrossing, optimizing their reproductive strategy in response to drug selection.

evolutionary biology↗

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↗

Variation in the response to antibiotics and life-history across the major Pseudomonas aeruginosa clone type (mPact) panel

Pseudomonas aeruginosa is a ubiquitous, opportunistic human pathogen. Since it often expresses multidrug resistance, it is ranked by the World Health Organization among the top 3 high priority pathogens, for which new treatment options are urgently required. An evaluation of new treatments is usually performed experimentally with one of the canonical laboratory strains (e.g., PAO1 or PA14). However, these two strains are unlikely representative of the strains infecting patients, because they have adapted to laboratory conditions and do not capture the enormous genomic diversity of the species. Here, we characterized the major P. aeruginosa clone type (mPact) panel. This panel consists of 20 strains, which reflect the genomic diversity of the species, cover all major clone types, and have both patient and environmental origins. We found significant strain variation in distinct responses towards antibiotics and general growth characteristics. Only few of the measured traits are related, and if so, only for specific antibiotics. Moreover, high levels of resistance were only identified for clinical mPact isolates and could be linked to known AMR (antimicrobial resistance) genes in the sequenced genomes. One strain also produced highly unstable AMR, indicating an evolutionary cost to resistance expression. By linking isolation source, growth, and virulence to life history traits, we further identified specific adaptive strategies for individual mPact strains towards either host processes or degradation pathways. Overall, the mPact panel provides a reasonably sized set of distinct strains, enabling in-depth analysis of new treatment designs or evolutionary dynamics in consideration of the species genomic diversity. ImportanceNew treatment strategies are urgently needed for high risk pathogens such as the opportunistic and often multidrug resistant pathogen Pseudomonas aeruginosa. Here, we characterize the major P. aeruginosa clone type (mPact) panel. It consists of 20 strains with different origins that cover the major clone types of the species as well as its genomic diversity. This mPact panel shows significant variation in (i) resistance against distinct antibiotics, including several last resort antibiotics, (ii) related traits associated with the response to antibiotics, and (iii) general growth characteristics. We further developed a novel approach that integrates information on resistance, growth, virulence, and life-history characteristics, allowing us to demonstrate the presence of distinct adaptive strategies of the strains that focus either on host interaction or resource processing. In conclusion, the mPact panel provides a manageable number of representative strains for this important pathogen for further in-depth analyses of treatment options and evolutionary dynamics.

microbiology↗

How antimicrobial heteroresistance promotes bacterial adaptation to antimicrobial therapy - or not

Withdrawal StatementThe authors have withdrawn their manuscript owing to inconsistencies of results during a re-assessment of the experimental work, which now question main conclusions drawn and which require additional experiments. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author

evolutionary biology↗

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↗

Environmental selection overrides host selection in a horizontally acquired microbiota

Horizontally acquired symbionts need to succeed both within hosts and the free-living environment. Microbes might invest differentially in these habitats, thus shaping fitness within host-associated microbiota communities. In this study, we investigated how host and environmental selection affect microbiota composition in a two-member model community of Pseudomonas lurida MYb11 and Ochrobactrum vermis MYb71 from the natural microbiota of Caenorhabditis elegans. Fitness characterizations in the host and non-host environment revealed distinct ecological strategies: while MYb11 dominated free-living by rapidly growing, it was quickly outcompeted within worms by MYb71. Using mathematical modeling and experimental evolution, we assessed how these distinct strategies affect microbiota composition over time. We found that MYb11 enriches in the host via its advantage in the environment and additionally adapts to the host. This community shift was mirrored in host fitness. Overall, this highlights the importance of the symbiont pool and shows that environmental selection can overwhelm host adaptation.

evolutionary biology↗

The intricate triangular interaction between protective microbe, pathogen, and host genetics determines fitness of the metaorganism

The microbiota shapes host biology in numerous ways. One example is protection against pathogens, which is likely critical for host fitness in consideration of the ubiquity of pathogens. The host itself can affect abundance of microbiota or pathogens, which has usually been characterised in separate studies. To date, however, it is unclear how the host influences the interaction with both simultaneously and how this triangular interaction determines fitness of the host-microbe assemblage, the so-called metaorganism. To address this current knowledge gap, we focused on a triangular model interaction, consisting of the nematode Caenorhabditis elegans, its immune-protective symbiont Pseudomonas lurida MYb11, and its pathogen Bacillus thuringiensis Bt679. We combined the two microbes with C. elegans mutants with altered immunity and/or microbial colonisation, and found that (i) under pathogen stress, immunocompetence has a larger influence on metaorganism fitness than colonisation with the protective microbe, (ii) in almost all cases, MYb11 still improves fitness, and (iii) disruption of p38 MAPK signalling, which contributes centrally to immunity against Bt679, completely reverses the protective effect of MYb11, which further reduces nematode survival and fitness upon infection with Bt679. Our study highlights the complex interplay between host genetics, protective microbe, and pathogen in shaping metaorganism biology.

evolutionary biology↗

Host and microbiome jointly contribute to adaptation to a complex environment

Most animals and plants have associated microorganisms, collectively referred to as their microbiomes, which can provide essential functions. Given their importance, host-associated microbiomes have the potential to contribute substantially to adaptation of the host-microbiome assemblage (the "metaorganism"). Microbiomes may be especially important for rapid adaptation to novel environments because microbiomes can change more rapidly than host genomes. However, it is not well understood how hosts and microbiomes jointly contribute to metaorganism adaptation. We developed a model system with which to disentangle the contributions of hosts and microbiomes to metaorganism adaptation. We established replicate mesocosms containing the nematode Caenorhabditis elegans co-cultured with microorganisms in a novel complex environment (laboratory compost). After approximately 30 nematode generations (100 days), we harvested worm populations and associated microbiomes, and subjected them to a common garden experiment designed to unravel the impacts of microbiome composition and host genetics on metaorganism adaptation. We observed that adaptation took different trajectories in different mesocosm replicates, with some increasing in fitness and others decreasing, and that interactions between host and microbiome played an important role in these contrasting evolutionary paths. We chose two exemplary mesocosms (one with a fitness increase and one with a decrease) for detailed study. For each example, we identified specific changes in both microbiome composition (for both bacteria and fungi) and nematode gene expression associated with each change in fitness. Our study provides experimental evidence that adaptation to a novel environment can be jointly influenced by host and microbiome.

evolutionary biology↗

Bacterial c-di-GMP plays a key role in the evolution of host-association

Most microbes evolve faster than their hosts and should therefore drive evolution of host-microbe interactions1-3. However, relatively little is known about the characteristics that define the adaptive path of microbes to host-association. In this study we have identified microbial traits that mediate adaptation to hosts by experimentally evolving the bacterium Pseudomonas lurida with the nematode Caenorhabditis elegans. We repeatedly observed the evolution of beneficial host-specialist bacteria with improved persistence in the nematode, achieved by mutations that uniformly upregulate the universal second messenger c-di-GMP. We subsequently upregulated c-di-GMP in different Pseudomonas species, consistently causing increased host-association. Comparison of Pseudomonad genomes from various environments revealed that c-di-GMP underlies adaptation to a variety of hosts, from plants to humans, suggesting that it is fundamental for establishing host-association.

evolutionary biology↗

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↗