Biology subjects

de Jonge, P.

Publications and source records attributed to de Jonge, P..

3 recordsLinked to original sources

bioRxiv2026

Diversity-generating retroelements enable phages to expand their host range in the human gut.

Diversity-generating retroelements (DGRs) are genetic elements that use error-prone reverse transcription to hypermutate specific target genes, most often the receptor-binding proteins of phages. They are enriched in human gut viruses, where they are hypothesised to enable phages expand their host range. Yet DGR-mediated host-range expansion across bacterial species has so far only been predicted in silico and has not been examined directly within complex microbial communities. To test this hypothesis in situ, we tracked phage-host interactions in the human gut, combining bulk metagenomic, virus-like particle (VLP), and Hi-C sequencing of longitudinal faecal samples collected over a five-week period. This culture-independent approach identified 380 interactions between 97 phages and 76 bacterial hosts. Nearly a third of these phages (31 of 97) encoded a DGR, and DGR-encoding phages were more likely to interact with multiple bacterial species. Moreover, nucleotide diversity in DGR-targeted genes increased with the number of hosts a phage interacted with and was concentrated in the surface-exposed, DGR-targeted variable region of its receptor-binding proteins. Together, these results provide in situ evidence that DGRs enable phages to expand their host range in the human gut.

microbiology↗

bioRxiv2025

Adipose Tissue Inflammation, Oxidative Stress, and Altered Adipogenesis Are Drivers of Dyslipidemia - A Multi-Omics Overview of Dyslipidemia in Obesity

BackgroundObesity is an important risk factor for cardiometabolic disease including dyslipidemia and atherosclerotic cardiovascular disease. While the role of the liver in dyslipidemia is established, the contribution of adipose tissue is less clear. This study aims to clarify the role of adipose tissue in lipid metabolism and its impact on dyslipidemia development. MethodsWe conducted a cross-sectional analysis of 125 patients from the BARIA longitudinal cohort study, consisting of patients with obesity undergoing bariatric surgery. Comprehensive phenotyping with fasting untargeted plasma metabolomics and lipid, lipoprotein, adipokine, RNA sequencing, and fecal sample shotgun metagenomic analysis was performed. We then compared tissue transcriptomic and plasma metabolites in individuals with and without dyslipidemia, exploring protective and pathogenic mechanisms. ResultsDyslipidemia was present in 43 patients (34.4%), with elevations in triglycerides, ApoB, and reductions in HDL-C and ApoAI. Plasma adipokines were less reliable markers of dyslipidemia: leptin levels were unexpectedly reduced in dyslipidemia, and after adjusting for gender, age, and body weight, adipokines did not differ between patients with and without dyslipidemia. In relation to plasma lipids or dyslipidemia, RNA sequencing identified altered gene expression of liver, jejunum, visceral and subcutaneous adipose tissue. Adipose tissue of patients with dyslipidemia was characterized by gene alterations of 3 pathways: inflammation, oxidative stress, and adipogenesis. Untargeted plasma metabolomics revealed associations of plasma lipids with endocannabinoid-like, secondary bile acid, plasmalogen, butyrate, and sphingolipid metabolites. Gut metagenome analysis in dyslipidemia found only correlation on bacterial order level. ConclusionsThis study provides novel insights into the role of adipose tissue in dyslipidemia of obesity. Our findings highlight the importance of not only visceral, but also subcutaneous adipose tissue in regulating plasma lipids. We found that fasting dyslipidemia associated with adipose tissue inflammation, oxidative stress, and altered adipogenesis, providing new insights into metabolic regulation of plasma lipids beyond hepatic pathways.

systems biology↗

bioRxiv2022

Single cell profiling reveals functional heterogeneity and serial killing in human peripheral and ex vivo-generated CD34+ progenitor derived Natural Killer cells

Increasing evidence suggest that Natural killer (NK) cells are composed of distinct functional subsets. This multi-functional role displayed by NK cells have made them an attractive choice for anti-cancer immunotherapy. A functional NK cell repertoire is generated through cellular education, resulting in heterogeneous NK cell population with distinct capabilities to respond to different stimuli. The application of a high-throughput droplet-based microfluidic platform allows monitoring of NK cell-target cell interactions at single-cell level and in real-time. Through fluorescence-based screening of around 80,000 droplets, with different Effector:Target ratios, a fully automated image analysis allows for the assessment of individual killing events in each droplet over time. We observed a variable response of single NK cells towards different target cells and identified a distinct population of NK cells capable of inducing multiple target lysis, coined as serial killers. To meet the increasing clinical demand for NK cells several sources, such as umbilical cord blood (UCB), have successfully been explored. By assessing the cytotoxic dynamics, we showed that single UCB-derived CD34+ hematopoietic progenitor (HPC)-NK cells display superior anti-tumor cytotoxicity. Additionally, with an integrated analysis of cytotoxicity and cytokine secretion we showed that target cell interactions augmented cytotoxic as well as secretory behavior of NK cells. By providing an in-depth assessment over NK cell functions, this study provides crucial information on diversity and functional characteristics of peripheral blood NK cells and ex vivo-generated HPC-NK cells to develop and improve of NK cell-based cancer immunotherapy.

immunology↗