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Zwinderman, A. H.

Publications and source records attributed to Zwinderman, A. H..

5 recordsLinked to original sources

Ethnic differences in gut microbiota composition and functional capacity persist over six years in the HELIUS multi-ethnic longitudinal cohort

Background: Ethnic minority groups in Western Europe carry a disproportionate cardiometabolic disease burden not fully explained by conventional risk factors, and their gut microbiomes differ markedly from those of European-origin populations. Whether these differences persist over time has not been examined prospectively. Results: We followed 1,903 participants from six ethnic groups in the HELIUS cohort over 6 years, using faecal 16S rRNA sequencing across all groups and shotgun metagenomics in a matched Dutch and South-Asian Surinamese subset (N = 238 per group). The extent of microbiota compositional change over time differed between ethnic groups: Moroccan participants showed the largest change, while the Dutch and South-Asian Surinamese participants were most stable. Diabetes mellitus and medication use at baseline were associated with greater compositional drift. However, ethnic differences in composition were largely preserved across all six groups (16S: ethnicity R2 0.044 to 0.037; all 15 pairwise contrasts significant at follow-up) and in the shotgun subset (R2 0.047 to 0.037). At the species level, 61 of 78 ethnicity-associated species remained differentially abundant at follow-up. Alistipes putredinis, the species converging most strongly, was absent at baseline in 43% of South-Asian Surinamese participants, and the convergence was consistent with acquisition of this species by this group. At strain level, within-person strain sharing declined with follow-up duration but was similar between ethnic groups. Within hosts, 90% of A. putredinis populations were retained as the same or a closely related lineage, and within the retained subset, microdiversity increased in both groups. Ethnic differences in functional profiles persisted to a similar extent as those in composition, with limited convergence in fibre-degrading enzyme families (GH5_37, GH26). The total antibiotic resistance gene (ARG) burden in the gut microbiome declined similarly in both groups over time. Dutch participants showed higher baseline ARG diversity that converged toward South-Asian Surinamese levels, while class-level differences were predominantly stable. Conclusions: Six years of follow-up in a shared urban environment narrowed ethnic differences in the gut microbiome only modestly; assuming exponential decline, the observed change corresponds to a half-life of roughly two decades.

microbiology↗

Phylogeny and disease links of a widespread and ancient gut phage lineage

Viruses are a core component of the human microbiome, impacting health and disease through interactions with gut bacteria1 and the immune system2. Most viruses in the human microbiome are bacteriophages, which exclusively infect bacteria. Individual gut bacteriophages can affect bacterial bile acid deconjugation3, and can alter their infection strategy based on dietary content4. Up to recently, most studies of the gut virome have focused on low taxonomic scales (e.g., viral operational taxonomic units), hampering population-level analyses. We previously identified the expansive and widespread Candidatus Heliusviridae bacteriophage family in a cohort with inhabitants of Amsterdam, the Netherlands. Here, we study their biodiversity and evolution in a wide variety of human populations. With a detailed phylogeny based on sequences from six viral genome databases, we now propose the Candidatus order Heliusvirales to accommodate these viruses. We identify Ca. Heliusvirales viruses in 80% of 5,441 individuals across 39 studies, and also in nine out of thirteen analyzed metagenomes from ancient humans that lived in Europe and North America between 1,000 and 5,000 years ago. We show that a large Ca. Heliusvirales lineage has diversified starting at the appearance of Homo sapiens some 200,000-300,000 years ago. Ancient peoples and modern hunter-gatherers further have distinct Ca. Heliusvirales populations that are characterized by lower richness than modern urbanized people. Within urbanized people, those suffering from type 1 and type 2 diabetes, as well as inflammatory bowel disease, have higher Ca. Heliusvirales richness than healthy controls. We thus conclude that these ancient core members of the human gut virome have thrived with increasingly westernized lifestyles of the human population.

microbiology↗

Members of a highly widespread bacteriophage family are hallmarks of metabolic syndrome gut microbiomes

There is significant interest in altering the course of cardiometabolic disease development via the gut microbiome. Nevertheless, the highly abundant phage members -which impact gut bacteria- of the complex gut ecosystem remain understudied. Here, we characterized gut phageome changes associated with metabolic syndrome (MetS), a highly prevalent clinical condition preceding cardiometabolic disease. MetS gut phageome populations exhibited decreased richness and diversity, but larger inter-individual variation. These populations were enriched in phages infecting Bacteroidaceae and depleted in those infecting Ruminococcaeae. Differential abundance analysis identified eighteen viral clusters (VCs) as significantly associated with either MetS or healthy phageomes. Among these are a MetS-associated Roseburia VC that is related to healthy control-associated Faecalibacterium and Oscillibacter VCs. Further analysis of these VCs revealed the Candidatus Heliusviridae, a highly widespread gut phage lineage found in 90+% of the participants. The identification of the temperate Ca. Heliusviridae provides a novel starting point to a better understanding of the effect that phages have on their bacterial hosts and the role that this plays in MetS.

microbiology↗

Predicting biological age based on the BBMRI-NL 1H-NMR metabolomics repository

The blood metabolome incorporates cues from the environment as well as the hosts genetic background, potentially offering a holistic view of an individuals health status. We have compiled a vast resource of 1H-NMR metabolomics and phenotypic data encompassing over 25,000 samples derived from 26 community and hospital-based cohorts. Using this resource, we constructed a metabolomics-based age predictor (metaboAge) to calculate an individuals biological age. Exploration in independent cohorts demonstrates that being judged older by ones metabolome, as compared to ones chronological age, confers an increased risk on future cardiovascular disease, mortality and functionality in older individuals. A web-based tool for calculating metaboAge (metaboage.researchlumc.nl) allows easy incorporation in other epidemiological studies. Access to data can be requested at bbmri.nl/samples-images-data. In summary, we present a vast resource of metabolomics data and illustrate its merit by constructing a metabolomics-based score for biological age that captures aspects of current and future cardio-metabolic health.

epidemiology↗

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, and identified variants in CCDC33 associated with susceptibility. Pneumococcal variation explained a large amount of invasive potential, but serotype explained only half of this variation. Newly developed methods identified pneumococcal genes involved in invasiveness including pspC and zmpD, and allowed a human-bacteria interaction analysis, finding associations between pneumococcal lineage and STK32C.

genomics↗