Biology subjects

Schneeberger, P.

Publications and source records attributed to Schneeberger, P..

5 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↗

bioRxiv2024

Discovery of a novel albendazole-ivermectin refractory Trichuris species, T. hominis, in C&ocircte d'Ivoire patients through fecal DNA metabarcoding

Albendazole-ivermectin combination therapy is a promising alternative to benzimidazole monotherapy for Trichuris trichiura control. We used fecal DNA metabarcoding to genetically characterize Trichuris populations in patients from a clinical trial showing lower albendazole-ivermectin efficacy in Cote dIvoire (ERR below 70%) than in Lao PDR and Tanzania (ERR above 98%). ITS-1 and ITS-2 rDNA metabarcoding revealed the entire Cote dIvoire Trichuris population was phylogenetically distinct from T. trichiura in Lao PDR and Tanzania, and more closely related to the porcine parasite Trichuris suis. Complete mitogenomes of eight adult Trichuris from Cote dIvoire confirmed their species-level differentiation. Corresponding Trichuris ITS-1 and ITS-2 sequences in NCBI from individual human patients in Cameroon and Uganda and three captive non-human primates suggest this newly recognized species, T. incognita, is distributed beyond Cote dIvoire and has zoonotic potential. Further work is needed to assess the impact of this Trichuris species on soil transmitted helminth control programs.

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↗

bioRxiv2021

Mega- and meta-analyses of fecal metagenomic studies assessing response to immune checkpoint inhibitors

PurposeGut microbiota have been associated with response to immune checkpoint inhibitors (ICI) including anti-PD-1 and anti-CTLA-4 antibodies. However, inter-study difference in design, patient cohorts and data analysis pose challenges to identifying species consistently associated with response to ICI or lack thereof. Experimental DesignWe uniformly processed and analyzed data from three studies of microbial metagenomes in cancer immunotherapy response (four distinct data sets) to identify species consistently associated with response or non-response (n=190 patient samples). Metagenomic data were processed and analyzed using Metaphlan v2.0. Meta- and mega-analyses were performed using a two-part modelling approach of species present in at least 20% of samples to account for both prevalence and relative abundance differences between responders/non-responders. ResultsMeta- and mega-analyses identified five species that were concordantly significantly different between responders and non-responders. Amongst them, Bacteroides thetaiotaomicron and Clostridium bolteae relative abundance (RA) were independently predictive of non-response to immunotherapy when data sets were combined and analyzed using mega-analyses (AUC 0.59 95% CI 0.51-0.68 and AUC 0.61 95% CI 0.52-0.69, respectively). ConclusionsMeta- and mega-analysis of published metagenomic studies identified bacterial species both positively and negatively associated with immunotherapy responsiveness across four published cohorts.

microbiology↗