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Microbes in Health and Disease (MHD)

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Pathogenic bacteria, fungi and viruses represent major threats to human health and wellbeing. Many of these microbes are especially dangerous for very young, frail elderly, immune-compromised or critically ill individuals, as well as patients with particular physiological or dermatological disorders. Notably, healthy individuals are also at risk, and this is most clearly evident in the less affluent regions of our planet where infectious diseases are still a major cause of morbidity and mortality. On the other hand, certain species of the human microbiota have potent health-promoting activities or barrier functions in the prevention of infections caused by pathogenic microbes. This imposes a clear need for fundamental, translational and clinical application-oriented research on the very diverse beneficial and detrimental roles of microbes in human health and disease (MHD). Since the dynamic behavior of biological systems is sustained by complex networks of interactions between their individual components, SyStems Biology approaches are used to integrate the results of interdisciplinary studies on microbes at the molecular, cellular, organism and community levels by theory-based and mathematical modelling. Importantly, pathogenic microbes do not respect national borders, and the MHD program is therefore embedded in a strong network of cross-border and international collaborations.

Scientific and Societal output   Dissertations  

See dissertations of MHD on horafinita.nl

Principal Investigators   Programme Leaders   Description of the Programme  

The MHD program has achieved ‘critical mass’ by bringing together expertise in four research areas of drug research that are key for preventing infections, fighting infections and harnessing the potentially beneficial effects of microbes:

The prevention of infectious diseases is an important integrative element in the research on bacterial, fungal and viral pathogens. This is achieved through pre-clinical and clinical research with the objective of preventing the emergence of highly-resistant microorganisms and new viruses by developing new interventions (prophylactic and otherwise) and drugs, and to validate the influence of measures for infection prevention. 

The bacteriological research addresses the mechanisms that lead to virulence and antibiotic resistance of a variety of dangerous human pathogens, as well as their risk profiles. The investigated pathogens include Staphylococcus aureus, Streptococcus pneumoniae, Porphyromonas gingivalis, mycobacteria, bacteria expressing extended spectrum β-lactamases (ESBL) or carbapenemases (CPE), and highly pathogenic and zoonotic enterohemorrhagic Escherichia coli. This research delivers novel targets for fast diagnostics, innovative preventive or therapeutic interventions with anti-microbial agents, human monoclonal antibodies or vaccines, and compounds that can serve in both therapeutic and diagnostic applications (theragnostics). A fundamental aspect of the bacteriological studies is the analysis of the secretome, which is a major reservoir of compounds that directly interact with the human host thereby influencing health in negative or positive ways. To obtain deeper insights into the roles of the secretome in bacterial fitness, growth, survival and antibiosis, Systems Biology approaches are applied. The transmission dynamics of bacterial pathogens are defined by modern network analyses and mathematical modelling to understand their global distribution and to pinpoint the ost effective intervention possibilities. Transmission and immunological aspects of bacterial colonization are also studied in close collaboration with dermatologists focusing on blistering diseases. Research in oral microbiology is focused on the role of anaerobic bacteria in oral diseases, such as periodontitis, peri-implant infections and endodontic infections, as well as non-oral diseases such as rheumatoid arthritis and the chronic destruction of hard and soft tissues. Related to bacterial infections afflicting less privileged populations, our research addresses tuberculosis and Buruli ulcer in various regions around the world with various partners, including the WHO. In ecological studies the dynamics of the human gut microbiota and interactions between bacteria are investigated, not only in relation to diseases like type I diabetes or Crohn’s disease, but also in response to interventions with antibiotics or prebiotics and probiotics. In this context, the beneficial gut microbe Faecalibacterium prausnitzii is studied as a potential probiotic for the promotion of gut health. 

The virological research addresses viral infections that represent major threats to human health. These include flaviviruses (dengue virus, West Nile virus) and other vector-borne viruses (Chikungunya virus), influenza and other respiratory viruses (respiratory syncytial virus [RSV], rhinovirus), tumor-associated viruses (human papilloma virus [HPV], hepatitis C virus [HCV]), and hepatitis E virus (HEV). The research activities range from unraveling virus-host cell interactions and development of prophylactic and therapeutic vaccines, to cancer immunotherapies and the establishment of new diagnostic tools and studies on virus epidemiology. State-of-the-art technologies (single-virus tracking, siRNA screens, systems immunology approaches, multiplex PCR etc.) are employed to better understand disease pathogenesis, to improve diagnostic possibilities and to identify possible targets for antiviral therapy, new vaccines and improved vaccination modes. This will enable timely diagnosis, and effective prophylaxis and/or therapy of viral infections in the future.

The epidemiological research addresses the behavior of bacterial and viral pathogens with a special focus on transmission, interactions between viruses and bacteria (primary and secondary infections), drug resistance and virulence. Mathematical modelling and network analyses are used to integrate the biological information with transmission dynamics in patient populations and the community. This has yielded predictive models of patho-adaptation and of the local (nosocomial), cross-border and global spreading of infectious diseases.

Mission  

The mission of the 'Microbes in Health and Disease' program is to define the detrimental and beneficial roles of microorganisms in human health and disease, and to exploit this knowledge in the prevention and fight against infectious diseases in order to promote healthy ageing. This will be achieved through the integration of fundamental, translational, clinical application and behavior-oriented drug research.

Relevance to Healthy Ageing  

The MHD research aimed at preventing or treating infectious diseases, and at sustaining or restoring a healthy microbiome, is highly relevant for the UMCG’s overarching theme of 5 healthy ageing. The respective research activities (see 1.2 and 2) target the following challenges: Europe and other developed regions have ageing societies that are increasingly susceptible to bacterial, fungal and viral infectious diseases. At the same time, antibiotic resistance, accelerated by insufficient antibiotic stewardship and drug abuse in veterinary practice, is developing fast and catching up with formerly effective measures to prevent or fight infections. Consequently, completely untreatable microbial infections and conditions like those in the 'pre-antibiotics era' are rapidly emerging, which will have a major impact on healthy ageingin the very near future. In developed countries, untreatable infections form an increasing threat for very young, frail elderly, immune-compromised and critically ill individuals. In less privileged parts of the world the burden of infectious diseases is much higher and here untreatable infections, including multidrug resistant tuberculosis (MDRTB) and viral epidemics, are serious threats, also for healthy individuals.