The microbiome constitutes the constellation of bacteria, archaea, fungi and viruses that inhabit the human body and play an essential for human health. Our team investigates factors that shape the microbiome, individual composition and stability of microbiome, its functional properties and relation to host and environmental factors, and its role in health.
Our research was initiated in 2016 by prof. dr. C. Wijmenga and prof. dr. Marten Hofker, and since then, we published numerous studies including several landmark papers in journals like Nature, Science, Cell, Nature Genetics, Science Translational Medicine and Gut. In these studies, we quantified inter-individual variation in microbial composition and functional properties and assessed to what extent microbial differences can be linked to intrinsic and exogenous factors, as well as host genetics. Our studies established microbial associations with cardio-metabolic traits, inflammatory bowel diseases, irritable bowel syndrome, cytokine production and other phenotypes. We also disentangled the effect of disease and medication on the gut microbiome and showed that the usage of non-antibiotic drugs can also affect our gut microbiome, such as proton pump inhibitors, anti-diabetics and laxatives. Furthermore, we have demonstrated that the gut microbiome itself is a complex trait that can be affected by host genetics, environmental factors and their interactions. Though some bacteria species are heritable, environmental factors dominate over genetics in shaping our gut microbiome, in particular dietary factors. Along with adult samples, we are investigating the microbiome during pregnancy and early life in the Lifelines-NEXT cohort: a collection of 1500 mothers and babies. We also explore the non-bacterial communities of the gut, including gut virome. Functional studies include culturing and characterization of specific bacterial strains. Our results are critical for the field for designing rational microbiota directed prevention and therapies.
While the research in last years had a strong focus on systems biology and multi-omics data analyses, the work is now extended with functional validation in model systems and wet-lab experiments.
Projects showcase
The Dutch Microbiome Project
The goal of the Dutch Microbiome Project is to investigate the interactions between microbiome, host, environment and human health. To achieve this goal, we are collaborating with Lifelines biobank to collect and analyze gut microbiome samples in ~10,000 participants from the Northern Netherlands at 5-year time intervals. Our first results of microbiome and microbiome-genetics studies are now available on the bioRxiv, and we are recently started microbiome and data collection for the first longitudinal follow-up study. Our data and results are available on the EGA and our DMP website.
Lifelines NEXT
Lifelines NEXT is a birth cohort designed to study the effects of intrinsic and extrinsic determinants on health and disease in a four-generation design. Approximately 1,500 pregnant women living in the Northern Netherlands are longitudinally followed starting at the third month of pregnancy. The collection of biomaterial and phenotypic data from mothers and their infants continues during the first year of life. The primary objective of Lifelines NEXT is to investigate the effects of pre-conceptional and early life factors on the health of infants and their mothers. Our main focus lies in the study of the interactions between gut, breastmilk, oral and vaginal microbiome and virome along with (epi)genetic, environmental and lifestyle factors. This study incorporating many multi-comic layers is a collaboration between the Departments of Genetics, Obstetrics & Gynecology, Pediatrics from the UMCG and Lifelines.
1000 IBD
The 1000IBD project is aimed at identification of novel treatments and therapies for inflammatory bowel diseases. To achieve this, we are investigating multiple ‘omics layers in ~1000 UMCG IBD patients.
1000IBD cohort was used in large number of research projects and some of our results include identification and quantification of dysbiosis in patients with IBD, quantification of changes in gut microbial pathways during flare-ups of IBD, models for microbiome-based diagnostics of IBD, identification of links between host exonic variants and microbiome and quantification of effect of diet to microbiome in IBD patients.
The first release of 1000IBD data is available on EGA and our dedicated 1000IBD website, and we are currently performing data collection for long-term follow-up of these patients
Lifelines-DEEP
Lifelines-DEEP has been the first multi-omics cohort built within Lifelines in 1,500 adults, initiated in 2012 and used in over 100 publications. The cohort was used to investigate relationship between environment, health, lifestyle and diverse -omics layers to explore how the genetic risk factors for disease affect gene expression, methylation, protein levels and the gut microbiome.
Current activities revolve around increasing the molecular breadth and depth, permitting further investigation
of different relationships between molecular layers.
Gut-on-a-chip
As a member of the NWO-funded Netherlands Organ-on-Chip Initiative (NOCI), we combine stem cells (iPSCs) with organ-on-chip technology. The stem-cell-derived intestinal epithelial cells (IECs) are cultivated in an Intestine-Chip, a microfabricated device with two compartments separated by a microporous membrane. The compartments can be perfused with fresh medium and flanking vacuum chambers are used to mimic peristaltic motion. Under those conditions, the IECs form a monolayer on the membrane that resembles intestinal villi observed in vivo. This model allows us to study the interaction of factors important for intestinal diseases – for example, interactions of microbiota-related molecules and immune cells.