Prof. Dennis Sandris Nielsen
University of Copenhagen
Department of Food Science
Professor Dennis Sandris Nielsen obtained his PhD from the Royal Veterinary and Agricultural University, Denmark, in 2006. After a post doc period at Department of Food Science, University of Copenhagen, he was appointed Associate Professor in 2010 and Professor 2017 the same place, where he is now heading the research group “Microbial diversity and function in gut and food”. During his entire research career focus has been on understanding microbial behavior in complex environments. Particular focus has been on fermented foods as well as understanding the association between the mammalian gut microbiome, health and disease and how GM is influenced by diet, bacteriophages, pre- and probiotics (in vivo and in vitro). After publishing his first paper in 2003, he has now published 211 papers in international, peer-reviewed journals.
The human gut microbiome and its influence on drug efficacy
The human gastro-intestinal tract is home to trillions of microorganisms. These microbes are collectively referred to as the gut microbiome (GM). The majority of these microbes reside in the colon. Bacteria are the main constituent of this complex community, but also archaea, unicellular eukaryotes and viruses (especially viruses having bacteria as their hosts, so-called bacteriophages) are important members of the GM. During the last 2 decades it has become increasingly clear, that GM imbalances (dysbiosis) are an important part of disease etiology of a long list of diseases ranging from obesity and type 2 diabetes over autoimmune diseases like asthma and type 1 diabetes to colon cancer.
The GM is key to human metabolism, as it provides energy and bioactives from otherwise indigestible parts of the diet such as fibers and indigestible carbohydrates. Interestingly, it has also during recent years been found, that the GM play pivotal roles in the efficacy of some orally delivered drugs. In some cases a prodrug is activated by gut microbial activity (examples include the antimicrobial compound prontosil and the anti-inflammatory drug sulfasalazine);
in other cases the active drug is inactivated by GM (e.g. the cardiac drug digoxin) and in some cases the GM even converts drugs into toxic compounds, as seen for some NSAIDs like ketoprofen, which following glucuronidation in the liver are excreted into the gut lumen, where microbial glucoronidases will produce toxic break-down products damaging the epithelial enterocytes. Further, during recent years it has been found, that the efficacy of certain anti-carcinogenic drugs against colorectal cancer is dependent on the GM composition of the patient.
Importantly, studies indicate, that via GM manipulation it is possible to enhance drug efficacy and safety. It is thus essential to understand GM-drug interactions to ensure optimal drug delivery and efficacy but also to avoid side-effects.