Project description DEENESFRITPL Investigating the complex relationship between gut microbiota and medicinal drugs The gut microbiota is a microbial community involved in developmental, immunological and metabolic functions in human hosts, and it also plays a role in medicinal drug response. The relationship between the gut microbiota and drugs is complex, and long-term exposure to drugs likely drives microbiome evolution. Human cohort studies suggest that non-antibiotic drugs also contribute to the emergence of antimicrobial resistance. The EU-funded DIMEvAR project aims to investigate the impact and consequences of long-term exposure to medicinal drugs on human gut microbiome evolution at the phenotypic and metabolic levels, and to elucidate the underlying molecular mechanisms, including the hypothesis that non-antibiotic drugs induce stress-triggered microbial evolution. Show the project objective Hide the project objective Objective The human gastrointestinal tract harbors trillions of microbes, known as the gut microbiota. This microbial community helps modulating developmental, immunological, and metabolic functions of the human host and it plays an important role in medicinal drug response. Several works showed the bidirectional relationship between the gut microbiota and drugs. Medication modifies microbiome composition both in vitro and in the human gut. Further, commonly used drugs influence the microbiome metabolic functions and increase the abundance of antimicrobial resistance (AMR) genes in human cohort studies, suggesting that non-antibiotic drugs could contribute to the emergence of AMR. At the same time, microbiome-encoded enzymes can metabolize a wide range of medical drugs, participating in both beneficial and adverse effects. Considering that many drugs are used over extended periods of time to treat chronic diseases, long-term exposure to drugs may likely drive microbiome evolution. This could influence and evolve metabolic properties of gut microbes and lead to the emergence of novel AMR.This project aims at better understanding the impact of long-term exposure to medical drugs on human gut microbiome evolution at the phenotypic and metabolic level, the underlying molecular mechanism, and their consequences in vivo. Based on previous data and in analogy to well-understood antibiotics, I hypothesize that non-antibiotic drugs might induce stress-triggered microbial evolution. The project follows three specific objectives: (i) Quantify the impact of drug-induced evolution on microbiome metabolism and antibiotic sensitivity; (ii) Determine the role of bacterial stress responses in microbiome evolution; (iii) Assess drug-induced microbiome evolution using gnotobiotic mouse models. If successful, this work will reveal the molecular mechanisms underlying microbiome-drug interactions and pave the way for their rational modulation to improve current and future drug therapies. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsnatural sciencesbiological sciencesmicrobiologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistancenatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2020 - Individual Fellowships Call for proposal H2020-MSCA-IF-2020 See other projects for this call Funding Scheme MSCA-IF-EF-CAR - CAR – Career Restart panel Coordinator EUROPEAN MOLECULAR BIOLOGY LABORATORY Net EU contribution € 262 209,60 Address Meyerhofstrasse 1 69117 Heidelberg Germany See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 262 209,60
