Biology subjects

Maier, L.

Publications and source records attributed to Maier, L..

At least 19 recordsLinked to original sources

bioRxiv2026

Lithocholic acid modulates the growth of butyrate-producing bacteria and is decreased in the feces of stunted children

Bile acids modulate the intestinal microbiota and serve as key signaling molecules in host physiology. Bile acid dysregulation has been implicated in nutritional and inflammatory diseases; however, data on the pool of bile acids present in stunted children or children suffering of environmental enteric dysfunction (EED) is limited, particularly in the upper intestinal compartment where disease phenotypes are most relevant. In this study, we performed a targeted metabolomics approach on 75 bile acids and their derivatives, including gastric and duodenal aspirates and fecal samples from almost 1000 children from two Sub-Saharan cities. We found that levels of secondary bile acids, especially lithocholic acid, are significantly lower in the feces of stunted and EED children, while ursocholic acid and its derivatives are significantly higher. Levels of primary and sulfated bile acids are also increased in the feces of children with EED. Microbiota sequencing revealed that high lithocholic acid levels are positively associated with butyrate-producing bacteria, while negatively associated with oral taxa like Streptococcus and Veillonella. In vitro tests on a panel of reference strains showed that oral bacteria bioaccumulate and are inhibited by a variety of bile acids, while lithocholic and chenodeoxycholic acids modulate the growth of several butyrate-producing bacteria. This effect was even stronger with tauro- or glycol-conjugated bile acids. Exposing stool-derived in vitro communities from children in Afribiota to these bile acids confirmed their positive impact on butyrate producers and negative effect on overgrowing oral taxa. Our findings suggest that secondary bile acids, reduced in stunting and EED, modulate the growth of butyrate-producing bacteria while suppressing harmful oral taxa, highlighting their potential as tools to modulate microbiota composition.

microbiology↗

bioRxiv2026

A host-directed virulence factor of Clostridium perfringens is modulated by gut commensal strains

In a healthy host, the residential microbes help regulate the growth of pathobionts, which are common members of the human gut microbiome, preventing them from causing diseases, including infections, under certain conditions. In cases of dysbiosis, this protection may be compromised. Targeted microbiome modulation offers a promising approach to restore healthy conditions in a disrupted community and consequently prevent infections using the natural colonization resistance of the microbiome. Elucidating the interaction mechanisms between microbial species within a microbiome is crucial for understanding how a microbiome can be modulated precisely and effectively to benefit the hosts well-being. Here, we investigated the interactions between the pathobiont C. perfringens and human gut commensals on physiological and molecular levels. We found that commensal strains affect C. perfringens growth by competing for substrates such as amino acids or a carbon source other than glucose. We further observed that Bacteroidaceae strains altered the levels of C. perfringens proteins, among others, the host-directed {theta}-toxin. Our findings reinforce the notion that modulating the composition of the gut microbiome is an effective strategy to prevent infections.

microbiology↗

bioRxiv2026

The role of IgE patterns and their link to the gut microbiome in allergic sensitization

Allergic diseases are heterogeneous conditions shaped by immune pathways and environmental influences, including the gut microbiome. Using cross-sectional data from 508 adults in the KORA FF4 cohort (275 with IgE sensitization, 233 without), we provide a multimodal statistical analysis of deep IgE profiles and concomitant gut microbial amplicon sequencing variant (ASV) data. We identified three latent allergy components in the cohorts IgE profiles that reflects food, pollen, and house dust mite markers and enables interpretable stratification of the cohort. Contrary to prior studies, microbial diversity did not differ between sensitized and non-sensitized individuals across all cohort strata. Differential abundance analysis identified 61 ASVs, with enrichment in Bacteroidaceae, Oscillospiraceae, and Veillonellaceae families, and depletion in the Lachnospiraceae family. Microbial network analysis further identified altered family-level associations in pollen- and food-sensitized individuals. Taxon set enrichment highlighted folic acid- and vitamin A-producing taxa, with consistent signals from Prevotella copri (depleted) and Bacteroides massiliensis (enriched). Together, our analysis points toward specific microbial families and metabolic groups as correlates of IgE sensitization in an adult population. HIGHLIGHTSO_LIIgE sensitization clusters reflect allergen sources and cross-reactive proteins C_LIO_LIThree latent allergy components capture the IgE profile structure of the entire cohort C_LIO_LIDistinct IgE patterns are linked to changes in taxa compositions and associations C_LIO_LIFolic acid- and vitamin A-producing taxa are enriched in IgE-sensitized individuals C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/714318v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1d1c8fborg.highwire.dtl.DTLVardef@1e1fea7org.highwire.dtl.DTLVardef@1589fcorg.highwire.dtl.DTLVardef@160282_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2026

A Functional Metabolomics Framework to Track Microbiome Drug Metabolism

Understanding how gut microbes transform drugs, and how this influences microbiome composition and function, remains a key question to better understand the efficacy and side effects of pharmaceuticals. To accelerate the discovery of microbiome-derived drug metabolites, we developed a functional metabolomics workflow that combines the use of synthetic microbial communities (SynComs) with a time-series resolved molecular networking approach and advanced computational metabolite annotation. We demonstrate how this framework can be used to illuminate chemical transformation dynamics in a gut SynCom (Com20) with 50 clinical drugs. Our results highlight a multitude of drug metabolites, including multi-step metabolic cascades, some of which correlated to shifts in microbial taxa, suggesting functional links between microbiome composition and biochemical transformations. Our computational data analysis workflow is publicly available through the GNPS2 ecosystem at chemprop.gnps2.org, which can be used to prioritize biotransformations and other (bio)chemical reactions in various biological and abiotic systems.

systems biology↗

bioRxiv2025

Flower clades and fruit clades: trade-offs in color diversification across angiosperms

PREMISEFlowers and fruits are two major phases of plant reproduction which often use colorful signals to attract animal mutualists. Fleshy fruits develop from the ovaries of flowers, and both organs use the same suites of pigments to create color. Due to these developmental links and functional similarities, we sought to test for correlations in flower and fruit color lability across clades. METHODSWe selected 51 clades (2989 species) of animal-pollinated and animal-dispersed plants and scored flower and fruit color into eight discrete (human-perceived) categories for the same set of species in each clade. We used stochastic character mapping to estimate the number and rates of transitions among colors in flowers and fruits. KEY RESULTSWe demonstrate a negative correlation in the number of transitions in flower and fruit color across clades (R2 = 0.48, p < 0.001). Among animal-pollinated and animal-dispersed clades, the majority (67%) are "fruit clades" biased towards fruit color lability, while a minority (29%) are "flower clades" biased towards flower color lability. We further show that clades with many yellow- or orange-flowered species also tend to have those colors in their fruits, and that red flowers are more common in "flower clades" while green and brown fruits are more common in "fruit clades". CONCLUSIONSThese patterns suggest that clades specialize on one phase of reproduction or the other. Possible explanations include constraints on energetic investment into either pollination or dispersal, and environmental factors that select for color diversification in one organ but not the other. This variation is also likely shaped by the underlying structure of pigment pathways that contribute to color in both organs.

evolutionary biology↗

bioRxiv2025

Flagellin in the human gut microbiome is a diet-adjustable adjuvant for vaccination

The intestinal microbiota is thought to modulate immune responsiveness to vaccines. Human studies on this topic, however, have yielded inconsistent results1,2. We hypothesized that the microbiome would influence innate immune responses, and thus vaccine reactogenicity, more directly than vaccine immunogenicity. To test this, we established the {micro}HEAT (Microbial-Human Ecology And Temperature) study, which longitudinally profiled the fecal microbiota, oral body temperature and serum antibody responses of 171 healthy adults (18-40 years old) before and after vaccination for SARS-CoV-2. Increased temperature after vaccination ({Delta}T) was associated with habitual diet and with baseline metabolic and immune markers. The microbiomes of {Delta}T-high ({Delta}Thi) participants were characterized by high expression of flagellin and an overabundance of the flagellated bacterium Waltera. Fecal samples from {Delta}Thi participants induced more inflammation in human cells and stronger post-vaccine temperature responses in mice compared to {Delta}Tlo samples, suggesting a causal role for the microbiome. Moreover, Waltera flagellin replicated the inflammatory phenotypes in vitro and was modulable via a dietary additive. Overall, these data suggest that flagellin from the gut microbiome stimulates innate immunity and vaccine reactogenicity, and that this axis can be manipulated via diet. These findings have implications for improving human vaccine tolerance and immunogenicity.

microbiology↗

bioRxiv2024

Extensive PFAS accumulation by human gut bacteria

Per- and polyfluoroalkyl Substances (PFAS) - the so-called forever chemicals - are a major cause of environmental and health concern due to their toxicity and long-term persistence1,2. Yet, no efficient mechanisms for their removal have been identified. Here we report bioaccumulation of PFAS by several gut bacterial species over a wide range of concentrations from nanomolar up to 500 M. For bioaccumulating Bacteroides uniformis, a highly prevalent species, we estimate intracellular PFAS concentration in the mM range - above that of most native metabolites. Despite this high bioaccumulation, B. uniformis cells could grow appreciably up to 250 M perfluorononanoic acid (PFNA) exposure. Escherichia coli, which accumulated PFAS to a much lesser extent, substantially increased PFAS bioaccumulation when lacking TolC efflux pump indicating trans-membrane transport in PFAS bioaccumulation. Electron microscopy and cryogenic Focused Ion Beam-Secondary Ion Mass-spectrometry revealed distinct morphological changes and intracellular localisation of PFNA aggregates. Bioaccumulation of PFAS and transmembrane transport is also evident in proteomics, metabolomics, thermal proteome profiling, and mutations following adaptive laboratory evolution. In an in vivo context, mice colonized with human gut bacteria showed, compared to germ-free controls or those colonized with low-bioaccumulating bacteria, higher PFNA levels in excreted feces. As the gut microbiota is a critical interface between exposure and human body, our results have implications for understanding and utilizing microbial contribution to PFAS clearance.

microbiology↗

bioRxiv2024

Off-purpose activity of industrial and agricultural chemicals against human gut bacteria

Contamination by industrial and agricultural chemicals like pesticides are a cause of great concern due to the risk to human and environmental health. While these chemicals are often considered to have restricted activity and are labelled as such, there are concerns over a broader toxicity range. Here we report the impact of 1076 pollutants spanning diverse chemistries and indicated applications on 22 prevalent commensal gut bacteria. Our systematic investigation uncovered 588 interactions involving 168 chemicals, the majority of which were not previously reported to have antibacterial properties. Fungicides and industrial chemicals showed the largest impact with circa 30% exhibiting anti-commensal properties. We find that the sensitivity to chemical pollutants across species surprisingly correlates with that to human-targeted drugs, suggesting common susceptibility mechanisms. Using a genome-wide chemical-genetic screen, we identified membrane transport and fatty acid metabolism as major modulators of the off-target toxicity of chemicals. Mutants exhibiting chemical resistance include those defective in producing human-health-relevant metabolites like branched short-chain fatty acids, indicating that chronic exposure could lead to selection against production of beneficial metabolites. Toxicokinetic modelling suggested gut bacteria could be used as more sensitive in vitro toxicity indicators for chemicals of concern than animal models. Together, our data uncovers the off-target activity of industrial and agricultural chemicals with widespread exposure against human gut bacteria. Impact on the structure and function of the microbiota should therefore be considered in assessing chemical safety.

microbiology↗

bioRxiv2024

Proton-pump inhibitors increase C. difficile infection risk by altering pH rather than by affecting the gut microbiome based on a bioreactor model

Clostridioides difficile infections often occur after antibiotic use, but they have also been linked to proton-pump inhibitor (PPI) therapy. The underlying mechanism--whether infection risk is due to a direct effect of PPIs on the gut microbiome or changes in gastrointestinal pH--has remained unclear. To disentangle both possibilities, we studied the impact of the proton-pump inhibitor omeprazole and pH changes on key members of the human gut microbiome and stool-derived microbial communities from different donors in vitro. We then developed a custom multiple-bioreactor system to grow a model human microbiome community in chemostat mode and tested the effects of omeprazole exposure, pH changes, and their combination on C. difficile growth within this community. Our findings show that changes in pH significantly affect the gut microbial communitys biomass and the abundances of different strains, leading to increased C. difficile growth within the community. However, omeprazole treatment alone did not result in such effects. These findings imply that the higher risk of C. difficile infection following proton-pump inhibitor therapy is probably because of alterations in gastrointestinal pH rather than a direct interaction between the drug and the microbiome. This understanding paves the way for reducing infection risks in proton-pump inhibitor therapy.

microbiology↗

bioRxiv2024

Baseline microbiome composition impacts resilience to and recovery following antibiotics

The gut microbiome of healthy individuals naturally undergoes temporal changes linked to the dynamics of its community components1. These dynamics are only observable in longitudinal studies; they are particularly relevant to understanding ecosystem responses to external environment disturbances. External exposures, such as antibiotic treatment, significantly reshape the gut microbiome, impacting both pathogen and commensal microbes2. The gut microbiome plays pivotal roles in digestion, nutrient absorption, and mental health, influencing immune systems, obesity, and various diseases3-6. Consequently, beyond the short-term effects on the host gut microbiome dynamics, alterations resulting from antibiotic exposure also have enduring repercussions on human health and physiological equilibrium7. Therefore, enhancing gut microbiome resilience during antibiotic treatment is essential, with the goal of mitigating prolonged adverse effects. Here, we explored the impact of pre-antibiotic microbial and functional profiles on resilience, suggesting that specific baseline features exhibit greater resilience to antibiotics-induced changes. Our results identified an uncultured Faecalibacterium prausnitzii taxon as a species at baseline associated with diminished resilience. We demonstrated that this association could be linked to the role of this F. prausnitzii taxon as a keystone species. Additionally, we observed the influence of other commensal bacteria, such as Bifidobacterium animalis and Lactobacillus acidophilus, as well as functional modules, such as multidrug resistance efflux pump, on resilience. This lays the foundations for designing targeted strategies to promote a resilient gut microbiome before antibiotic treatment, alleviating possible prolonged effects on human health.

microbiology↗

bioRxiv2024

An anti-virulence drug targeting the evolvability protein Mfd protects against infections with antimicrobial resistant ESKAPE pathogens

The increased incidence of antibiotic resistance and declining discovery of new antibiotics have created a global health crisis, especially for the treatment of infections caused by Gram-negative bacteria. Here, we identify and characterize a molecule, NM102, that displays antimicrobial activity exclusively in the context of infection. NM102 inhibits the activity of the non-essential Mutation Frequency Decline (Mfd) protein by competing with ATP binding to its active site. Inhibition of Mfd by NM102 sensitizes pathogenic bacteria to the host immune response and blocks infections with clinically- relevant Klebsiella pneumoniae and Pseudomonas aeruginosa, without inducing host toxicity. Finally, NM102 inhibits the function of Mfd as a mutation and evolvability factor, thus reducing the bacterial capacity to develop antimicrobial resistance. These data provide a potential roadmap to expand the arsenal of drugs to combat antimicrobial resistance. HighlightO_LINM102 is a "first in class" molecule specifically targeting the active site of the bacterial Mfd protein C_LIO_LINM102 has a new mode of action: it inhibits Mfd function during immune stress response C_LIO_LINM102 also inhibits Mfd evolvability function and thereby decreases bacterial resistance to known antibiotics C_LIO_LINM102 effectively treats Gram-negative infections in animal models C_LIO_LINM102 is efficient against clinically relevant resistant bacteria and provides an increased efficacy in combination with the {beta}-lactam meropenem C_LI

microbiology↗

bioRxiv2023

Non-antibiotic drugs break colonization resistance against pathogenic Gammaproteobacteria

Non-antibiotic drugs can alter the composition of the gut microbiome, with largely undefined implications for human health. Here we compared the susceptibility of commensal and pathogenic bacteria to non-antibiotic drugs and found that pathogens show higher drug resistance, which could favor their expansion after treatment. We then developed a model system to screen for drug-microbiome interactions that increase the risk of enteropathogenic infections. Approximately 35% of the >50 drugs we tested increased the abundance of Salmonella Typhimurium in synthetic and human stool-derived microbial communities. This was due to direct effects of non-antibiotics on individual commensals, altered microbial interactions within communities and the potential of Salmonella to exploit different metabolic niches. Non-antibiotic drugs that favored Salmonella expansion in vitro also promoted other enteric pathogens and increased Salmonella loads in gnotobiotic and conventional mice. These findings may inform future strategies to control pathogen proliferation and to assess individual microbiota-drug-pathogen risks for infection.

microbiology↗

bioRxiv2023

Functional Tissue Units in the Human Reference Atlas.

Functional tissue units (FTUs) form the basic building blocks of organs and are important for understanding and modeling the healthy physiological function of the organ and changes during disease states. In this first comprehensive catalog of FTUs, we document the definition, physical dimensions, vasculature, and cellular composition of 22 anatomically correct, nested functional tissue units (FTUs) in 10 healthy human organs. The catalog includes datasets, illustrations, an interactive online FTU explorer, and a large printable poster. All data and code are freely available. This is part of a larger ongoing international effort to construct a Human Reference Atlas (HRA) of all cells in the human body.

bioinformatics↗

bioRxiv2023

Emergence of community behaviors in the gut microbiota upon drug treatment

Pharmaceuticals can directly inhibit the growth of gut bacteria, but the degree such interactions manifest in complex community settings is an open question. Here we compared the effects of 30 drugs on a 32-species synthetic community with their effects on each community member in isolation. While most individual drug-species interactions remained the same in the community context, communal behaviors emerged in 26% of all tested cases. Cross-protection, during which drug-sensitive species became protected in community, was 6-times more frequent than cross-sensitization, the converse phenomenon. Cross-protection decreased and cross-sensitization increased at higher drug concentrations, suggesting that the resilience of microbial communities can collapse when perturbations get stronger. By metabolically profiling drug-treated communities, we showed that both drug biotransformation and bioaccumulation contribute mechanistically to communal protection. As a proof-of-principle, we molecularly dissected a prominent case: species expressing specific nitroreductases degraded niclosamide, thereby protecting both themselves and sensitive community members.

microbiology↗

bioRxiv2023

Consistency across multi-omics layers in a drug-perturbed gut microbial community

Multi-omics analyses are increasingly employed in microbiome studies to obtain a holistic view of molecular changes occurring within microbial communities exposed to different conditions. However, it is not always clear to what extent each omics data type contributes to our understanding of the community dynamics and whether they are concordant with each other. Here we map the molecular response of a synthetic community of 32 human gut bacteria to three non-antibiotic drugs by using five omics layers, namely 16S rRNA gene profiling, metagenomics, metatranscriptomics, metaproteomics, and metabolomics. Using this controlled setting, we find that all omics methods with species resolution in their readouts are highly consistent in estimating relative species abundances across conditions. Furthermore, different omics methods complement each other in their ability to capture functional changes in response to the drug perturbations. For example, while nearly all omics data types captured that the antipsychotic drug chlorpromazine selectively inhibits Bacteroidota representatives in the community, the metatranscriptome and metaproteome suggested that the drug induces stress responses related to protein quality control and metabolomics revealed a decrease in polysaccharide uptake, likely caused by Bacteroidota depletion. Taken together, our study provides insights into how multi-omics datasets can be utilised to reveal complex molecular responses to external perturbations in microbial communities.

microbiology↗

bioRxiv2022

Comparing the efficiency of six clearing methods in developing seeds of Arabidopsis thaliana

Tissue clearing methods eliminate the need for sectioning, thereby helping better understand the 3D organization of tissues and organs. In the past fifteen years, clearing methods have been developed to preserve endogenous fluorescent protein tags. Some of these methods (ClearSee, TDE, PEA-Clarity, etc.) were adapted to clear various plant species, with the focus on roots, leaves, shoot apical meristems, and floral parts. However, these methods have not been used in developing seeds beyond the early globular stage. Tissue clearing is problematic in post-globular seeds due to various apoplastic barriers and secondary metabolites. In this study, we compared six methods for their efficiency in clearing Arabidopsis thaliana seeds at post-globular embryonic stages. Three methods (TDE, ClearSee, and ClearSee alpha) have been already reported in plants whereas the others (fsDISCO, FAST9, and CHAPS clear) are used in this context for the first time. These methods were assessed for seed morphological changes, clearing capacity, removal of tannins, and spectral properties. We tested each method in seeds from globular to mature stages. The pros and cons of each method are listed herein. ClearSee alpha appears to be the method of choice as it preserves seed morphology and prevents tannin oxidation. However, FAST9 with 60% iohexol as a mounting medium is faster, clears better, and appears suitable for embryonic shape imaging. Our results may guide plant researchers to choose a suitable method for imaging fluorescent protein-labeled embryos in intact Arabidopsis seeds. Key messageClearSee alpha and FAST9 were optimized for imaging Arabidopsis seeds up to the torpedo stages. The methods preserve the fluorescence of reporter proteins and seed shape, allowing phenotyping embryos in intact seeds.

plant biology↗

bioRxiv2022

Modulation of bacterial cell size and growth rate via activation of a cell envelope stress response

Fluctuating conditions and diverse stresses are typical in natural environments. In response, cells mount complex responses across multiple scales, including adjusting their shape to withstand stress. In enterobacteria, the Rcs phosphorelay is activated by cell envelope damage and by changes to periplasmic dimensions and cell width. Here, we investigated the physiological and morphological consequences of Rcs activation in Escherichia coli in the absence of stresses, using an inducible version of RcsF that mislocalizes to the inner membrane, RcsFIM. Expression of RcsFIM immediately reduced cellular growth rate and the added length per cell cycle in a manner that was directly dependent on induction levels, but independent of Rcs-induced capsule production. At the same time, cells increased intracellular concentration of the cell division protein FtsZ, and decreased the distance between division rings in filamentous cells. Depletion of the Rcs negative regulator IgaA phenocopied RcsFIM induction, indicating that IgaA is essential due to growth inhibition in its absence. However, A22 treatment did not affect growth rate or FtsZ intracellular concentration, despite activating the Rcs system. These findings suggest that the effect of Rcs activation on FtsZ levels is mediated indirectly through growth-rate changes, and highlight feedbacks among the Rcs stress response, growth dynamics, and cell-size control.

microbiology↗

bioRxiv2020

Multimodal and multisensory coding in the Drosophila larval peripheral gustatory center

The ability to evaluate food palatability is innate in all animals, ensuring their survival. The external taste organ in Drosophila larvae is composed of only few sensory neurons but enables discrimination between a wide range of chemicals and displays high complexity in receptor gene expression and physiological response profile. It remains largely unknown how the discrepancy between a small neuronal number and the perception of a large sensory space is genetically and physiologically resolved. We tackled dissection of taste sensory coding at organ level with cellular resolution in the fruit fly larva by combining whole-organ calcium imaging and single-cell transcriptomics to map physiological properties and molecular features of individual neurons. About one third of gustatory sense neurons responded to multiple tastants, showing a rather large degree of multimodality within the taste organ. Further supporting the notion of signal integration at the periphery, we observed neuronal deactivation events within simultaneous neighboring responses, suggesting inter-cellular communication through electrical coupling and thus providing an additional level in how neurons may encode taste sensing. Interestingly, we identified neurons responding to both mechanical and taste stimulation, indicating potential multisensory integration. On a molecular level, chemosensory cells show heterogeneity in neuromodulator expression. In addition to a broad cholinergic profile, markers on dopaminergic, glutamatergic or neuropeptidergic pathways are present either in distinct cell populations or are seemingly co-expressed. Our data further extend the sensory capacity of the larval taste system pointing towards an unanticipated degree of multimodal and multisensory coding principles.

neuroscience↗