Biology subjects

Dommann, J.

Publications and source records attributed to Dommann, J..

7 recordsLinked to original sources

bioRxiv2026

Natural microbial exposure imposes layered constraints on epithelial and type 2 immunity

The tuft cell-ILC2 amplification circuit has emerged as a central paradigm of anti-helminth immunity in laboratory animals, driving the so-called weep and sweep response, required for parasite expulsion. Yet soil-transmitted helminths (STHs) commonly establish chronic infections in humans. Whether tuft cell expansion is required for parasite clearance under naturalistic conditions remains unknown. Here, using wildlings, a naturalized mouse model exposed from birth to complex microbial communities and pathogens, we re-investigated anti-STH immunity in the context of ecological realism. Following infection with Nippostrongylus brasiliensis, specific pathogen-free (SPF) mice mounted markedly amplified type 2 responses in both lung and intestine compared to wildlings. In the intestine, SPF mice mounted robust tuft cell expansion, IL-25 production, ILC2 accumulation, and goblet cell hyperplasia. In contrast, infected wildlings exhibited delayed parasite expulsion, limited tuft cell expansion, reduced IL-25 and ILC2 responses, and attenuated goblet cell expansion. Wildling tuft cells, but not goblet cells, displayed markedly reduced expansion in response to succinate or exogenous IL-13, indicating selective hypo-responsiveness of the epithelial sensory compartment. Microbial transfer into adult SPF mice selectively conferred tuft cell hypo-responsiveness without impairing ILC2 accumulation or goblet cell expansion. Tuft cell hypo-responsiveness in wildlings and FMT recipients was associated with enrichment of fermentative bacteria and increased levels of the short chain fatty acids acetate and propionate. Together, these findings indicate that ecological microbial exposure imprints systemic type 2 immunity during early-life, whereas epithelial responsiveness remains plastic and microbiome-dependent, thereby revealing regulatory constraints not evident under SPF conditions. One Sentence SummaryOur findings reveal that in a naturalized immune-microbiome context, intestinal tuft cells are surprisingly hypo-responsive, highlighting how environmental microbial exposure can calibrate type 2 immunity and helminth resistance.

immunology↗

bioRxiv2026

The antiparasitics ivermectin and moxidectin trigger genomic and transcriptomic adaptation in bacteria

The macrocyclic lactone anthelmintics ivermectin and moxidectin are widely used for parasite control and show antibacterial activity in vitro. Given their structural relatedness to macrolide antibiotics, their broad use raises concerns about macrolide cross-resistance and altered bacterial physiology, yet the impact on gut bacterial isolates and underlying mechanisms remains poorly defined. Here, we combined Oxford Nanopore whole genome sequencing with Illumina RNA sequencing across six bacterial isolates analyzed as unexposed controls and as derivatives repeatedly exposed to ivermectin or moxidectin to identify genomic and transcriptomic signatures associated with exposure to these drugs. High-quality genome assemblies enabled integrated analyses across species with distinct cellular architectures and antimicrobial resistance gene arsenals. Across the panel, exposure was associated with i) widespread modulation of ribosome-linked genes and pathways, the molecular target of macrolide antibiotics; ii) context-dependent tuning of pre-existing antimicrobial resistance gene arsenals, such as macB and mdlB; and iii) recurrent alterations in potassium transport systems (ktrA and trkA). These findings suggest that repeated ivermectin or moxidectin exposure can reshape bacterial physiology in ways that may, in specific genetic backgrounds, co-modulate resistance-associated traits.

microbiology↗

bioRxiv2025

Hybrid-metagenomics reveal off-target effects of albendazole, ivermectin-albendazole and moxidectin-albendazole on the human gut bacteria.

The human whipworm parasite, Trichuris trichiura, poses a critical public health problem, affecting over 400 million people globally and responding poorly to the standard-of-care - benzimidazole chemotherapy. Recent efforts aimed at developing improved treatment options, the two macrolide-benzimidazole combination therapies ivermectin-albendazole and moxidectin-albendazole. Recent reports suggest that ivermectin and moxidectin possess antibacterial properties in vitro, hence there is a need to comprehensively characterize their off-target effects on the gut microbiome. In the framework of a randomized-controlled trial we collected stool samples of 204 T. trichiura-infected individuals in Cote dIvoire receiving albendazole (400mg), albendazole-ivermectin (400mg/200{micro}g/kg) and albendazole-moxidectin (400mg/8mg). Using a state-of-the-art hybrid sequencing approach that combines Illumina short read and Oxford Nanopore long read shotgun sequencing, we recovered over 800 high-quality metagenome-assembled genomes. Our analyses reveal that albendazole and albendazole-moxidectin induce taxonomic shifts in the gut microbiota with only mild functional consequences. In contrast, in individuals receiving higher quantities of albendazole-ivermectin (ivermectin > 12mg), based on their weight, we observed profoundly modulated taxonomic composition and microbial function, while the resistome was largely spared. These findings robustly confirm ivermectins antibacterial properties in the human gut, extending beyond previously reported in vitro effects. Given that ivermectin is a cornerstone in parasitic disease control, it is crucial to evaluate its broader impacts and considering more targeted, evidence-based treatment strategies.

genomics↗

bioRxiv2025

Profound taxonomic and functional gut microbiota alterations associated with trichuriasis: cross-country and country-specific patterns

BackgroundThe human gastrointestinal microbiota plays a crucial role in immune modulation, metabolism, and pathogen resistance. Soil-transmitted helminth (STH) infections, including Trichuris trichiura (whipworm), significantly alter gut microbial composition, yet the extent and functional consequences of these changes remain underexplored across different geographical regions. This study investigates the taxonomic and functional impacts of T. trichiura on gut microbiota in three endemic regions - Cote dIvoire, Laos, and Tanzania - using a unified high-resolution metagenomic sequencing approach. ResultsThis study reveals extensive gut microbiota disruptions linked to T. trichiura infection, with both regional and cross-country patterns. A core signature found across all study sites includes depletion of Faecalibacterium prausnitzii and Eubacterium rectale (Short-chain fatty acids (SCFA) producers) and enrichment of mucin-degrading bacteria (Ruminococcus, Bacteroides), alongside increased host-derived carbohydrate metabolism. Infection destabilized microbial networks, characterized by reduced connectivity and clustering, with opportunistic taxa such as Segatella copri emerging as network hubs across regions, indicating a shared ecological response. Both taxonomic and functional disruptions exhibited a combination of conserved and region-specific patterns; for example, whereas certain taxa, such as Prevotella and Streptococcus, showed notable geographic variability, specific functional changes, such as SCFA depletion and mucin degradation, were consistently observed across sites. These conserved functional changes suggest that T. trichiura imposes similar metabolic pressures on the gut microbiome across populations, potentially affecting host nutrient availability and immune responses in a predictable manner. Discussion and ConclusionThis study provides robust evidence that T. trichiura infection induces significant and consistent microbiome alterations across diverse populations. The depletion of SCFA-producing bacteria and the enrichment of mucin-degrading taxa, along with corresponding metabolic pathways, imply compromised gut barrier integrity, providing insights into the complex inflammatory processes associated with this helminth infection. Additionally, these microbiome differences could play a critical role in facilitating parasite persistence and reinfection, which remain major challenges limiting the efficacy of global control strategies. Our findings highlight the potential of microbiome-targeted interventions, such as probiotic supplementation or dietary modifications, to mitigate the health impacts of T. trichiura infections by restoring microbial homeostasis.

microbiology↗

bioRxiv2024

Nanopore-based analysis unravels the genetic landscape and phylogenetic placement of human-infecting Trichuris species in Cote d'Ivoire, Tanzania, Uganda, and Laos

Soil-transmitted helminthiases, particularly trichuriasis, affect over 500 million people, mostly in low- and middle-income countries. Traditional diagnostics fail to distinguish between Trichuris species, obscuring transmission patterns and treatment outcomes. Using nanopore-based full-length ITS2 rDNA sequencing, we analyzed 687 samples from Cote dIvoire, Laos, Tanzania, and Uganda, confirming the phylogenetic placement of Trichuris trichiura and the recently described Trichuris incognita. We identified two genetically distinct Trichuris species infecting humans, with divergent geographic patterns and presence in non-human primates, suggesting complex host-parasite dynamics. Within-country genetic variation indicated local adaptation and cryptic population structure. Importantly, we demonstrated that ITS2 fragment length is a robust, cost-effective diagnostic marker for differentiating T. incognita and T. trichiura, offering a practical alternative to sequencing for resource-limited settings. These findings expose the hidden complexity of Trichuris infections and highlight the urgent need to update diagnostic and control strategies to account for overlooked species diversity in endemic regions.

genomics↗

bioRxiv2024

A novel barcoded nanopore sequencing workflow of high-quality, full-length bacterial 16S amplicons for taxonomic annotation of bacterial isolates and complex microbial communities

IntroductionDue to recent improvements, Nanopore sequencing has become a promising method for experiments relying on amplicon sequencing. We describe a flexible workflow to generate and annotate high-quality, full-length 16S rDNA amplicons. We evaluated it for two applications, namely, i) identification of bacterial isolates and ii) species-level profiling of microbial communities. MethodsBacterial isolate identification by sequencing was tested on 47 isolates and compared to MALDI-TOF MS. 97 isolates were additionally sequenced to assess the resolution of phylogenetic classification. Species-level community profiling was tested with two full-length 16S primer pairs (A and B) with custom barcodes and compared to results obtained with Illumina sequencing using 27 stool samples. Finally, a Nextflow pipeline was developed to produce high-quality reads and taxonomically annotate them. ResultsWe found high agreement between our workflow and MALDI-TOF data for isolate identification (PPV = 0.90, Cramers V = 0.857 and, Theils U = 0.316). For species-level community profiling, we found strong correlations (rs > 0.6) of alpha diversity indices between the two primer sets and Illumina sequencing. At the community level, we found significant but small differences when comparing sequencing techniques. Finally, we found moderate to strong correlation when comparing relative abundances of individual species (average rs = 0.6 and 0.533, for primers A and B). DiscussionThe proposed workflow enabled accurate identification of single bacterial isolates, making it a worthwhile alternative to MALDI-TOF. While shortcomings have been identified, it enabled reliable identification of prominent features in microbial communities at a fraction of the cost of Illumina sequencing. ImportanceA quick, robust, simple, and cost-effective method to identify bacterial isolates and communities in each sample is indispensable in the fields of microbiology and infection biology. Recent technological advances in Oxford Nanopore Technologies sequencing make this technique an attractive option considering the adaptability, portability, and cost-effectiveness of the platform. Here, we validated a flexible workflow to identify bacterial isolates and characterize bacterial communities using the Oxford Nanopore Technologies sequencing platform combined with the most recent v14 chemistry kits. For bacterial isolates, we compared our nanopore-based approach to MALDI-TOF MS-based identification. For species-level profiling of complex bacterial communities we compared our nanopore-based approach to Illumina shotgun sequencing. For reproducibility purposes, we wrapped the code used to process the sequencing data into a ready-to-use and self-contained Nextflow pipeline.

microbiology↗

bioRxiv2024

Exposure of gut bacterial isolates to the anthelminthic drugs, ivermectin and moxidectin, leads to antibiotic-like phenotypes of growth inhibition and adaptation.

Due to their broad-spectrum activities, ivermectin and moxidectin are widely used anthelminthics in veterinary and human medicine. However, ivermectin has recently been shown to perturbate gut-microbial growth. Given the macrolide-like structure of both ivermectin and moxidectin, there is a need to characterize the antibiotic spectrum of these anthelminthic drugs and their potential implications in the development of cross-resistance to macrolides and other families of antibiotics. Here, we incubated 59 bacterial isolates representing different clades frequently found in the gut with ivermectin and moxidectin at different concentrations for 16-72h. Further, we challenged 10 bacterial isolates with repeated and gradually increasing concentrations of these two anthelminthics and subsequently characterized their sensitivity to different antibiotics as well as ascending anthelminthic concentrations. We found, that antibacterial activity of the two anthelminthics is comparable to a selection of tested antibiotics, as observed by potency and dose dependence. Bacterial anthelminthic challenging in vitro resulted in decreased anthelminthic sensitivity. Further, adaptation to anthelminthics is associated with decreased antibiotic sensitivity towards three macrolides, a lincosamide, a fluoroquinolone, a tetracycline and two carbapenems. The observed change in bacterial sensitivity profiles is associated with - and likely caused by - repeated anthelminthic exposure. Hence, current and future large-scale administration of ivermectin and moxidectin, respectively, for the control of helminths and malaria raises serious concerns - and hence potential off-target effects should be carefully monitored.

microbiology↗