Microbes, also called microorganisms, are omnipresent in our lives, even if we do not see them. Microorganisms include bacteria, fungi, archaea, protists and viruses, and are among the earliest known life forms. They can be beneficial or harmful to their host, depending on their environment and the properties conferred by their genomic content. Depending on the biological context, we might want to eradicate them, using new antibiotics strategies, or to promote the growth of some of them to harness their biological properties.
Does the microbiota-host crosstalk contribute the metabolic disorders occurring in cancer?
Cancer cachexia regroups a pattern of metabolic disorders occurring in cancer. This complex and highly invalidating disease remains an unmet medical need for which new therapeutic tools are warranted. Prof L. Bindels and her team are currently investigating the role and therapeutic interest of gut microbes, bacterial metabolites and microbiota-targeting foods in cancer cachexia. We combine metabolomics, next-generation sequencing and integrative physiology to dissect the relationship between gut microbes and their host in this specific context. With this project, we aim to deliver innovative nutritional and pharmacological tools that would ultimately provide a better supportive care to cancer patients.
How can we harvest the metabolic potential of the gut microbiota-host crosstalk to tackle obesity, metabolic syndrome, and cardiovascular disease?
Obesity, metabolic disorders and cardiovascular diseases have reached epidemic proportions over the last decade and new innovative tools, both at the preventive and therapeutic levels, are warranted. The gut microbiota plays a key role in energy homeostasis and metabolic regulation. By combining preclinical and clinical studies, Profs. Delzenne, Cani and their teams are dedicating their efforts to the evaluation of the interest and role of the gut microbiota as a therapeutic target to tackle obesity, metabolic syndrome, and cardiovascular disease. Current clinical studies such as Microbes4U and Food4Gut will help answering the key question of the relevance of innovative tools targeting the gut microbiota in obesity.
What are the mechanisms by which the innate immune system, bioactive lipids and the gut microbiota control host metabolism?
Obesity is characterized by cardio-metabolic risk factors (e.g., inflammation, hepatic steatosis, type 2 diabetes). Our pioneering studies have shown that gut microbes contribute to these disorders likely by modulating immunity, but also bioactive lipids production including endocannabinoids. Prof Cani and his team have developed several unique models (e.g., inducible cell specific deletion, pharmacological tools, organoids) targeting key enzymes/receptors linked with the endocannabinoid system, lipid congeners or specific immune response. Our project will allow us to unravel several axis of communication between the gut and peripheral organs such as the brain, the liver, and the adipose tissue and their role on energy, glucose, lipid metabolism, and inflammation.
Which benefits can be conferred by nutrients targeting the gut microbiota?
The nutrition plays a key role in energy homeostasis and, metabolic regulation, namely by influencing the gut microbiota . Projects led by Prof Delzenne and her team aim to investigate the interest of some food ingredients (also known as prebiotics) which specifically target the gut microbiota in metabolic disorders. These projects focus on the understanding of the mechanisms by which nutrients can confer benefits to the host by modulating the gut microbiota activity and composition, thereby promoting the production of bacterial metabolites prone to interact with key host functions (i.e. short chain fatty acids, microbial derived conjugated fatty acids, bile acids).
Is the gut microbiota controlling food intake and food behavior of the host?
The concept of the implication of the gut microbiota in the gut-to-brain axis to control food intake emerged over these last years, however the mechanisms still remain incompletely known. During obesity, the gut-to-brain axis is altered leading to an abnormal increase in energy consumption. Prof Everard and her team are studying the alterations of the gut-to-brain axis to control food intake during obesity and the implication of the gut microbiota in that context. The originality of this work is to investigate how gut microbes are able to control hedonic and reward system in healthy conditions as well as in the physiopathology of obesity.
Which compounds make some plants used in traditional medicine really effective and what are their therapeutic perspectives?
The main objective of our research team is to identify and isolate pharmacologically active products in plants from different countries and validate their traditional uses. We chose to focus particularly on medicinal plants and their constituents with antimicrobial (on Staphylococcus aureus, Pseudomonas aeruginosa, …) and antiparasitic (on Trypanosoma, Plasmodium, Leishmania) activities, as well as compounds inhibiting bacteria/parasites resistance, and to study their targets. These works are especially realized in collaboration with TFAR.
Contact : Joëlle Quetin-Leclercq (GNOS)
How to control the quality of natural products for a standardized activity
The right identification and quality controls of raw materials and plant extracts are crucial to guarantee their efficacy and safety. Quantification of these compounds in biological fluids is also necessary for further studies. Therefore, our team develops and validates methods to separate, identify and quantify active molecules in plant extracts or biological fluids based on different chromatographic techniques (HPTLC-MS, UHPLC-DAD, MS and MRMS, GC-FID, GC-MS). Moreover, the laboratory is officially agreed by the Federal Agency for Medicine and Health Products for the quality control of drugs. Contact : Joëlle Quetin-Leclercq
Is it possible to improve the safety and the efficacy of existing anti-HIV drugs by personalizing the therapeutic arsenal proposed to each patient given his specific genetic and non-genetic profile?
HIV treatment is challenging not only due to the high propensity for drug-drug interaction between antiretrovirals but also due to interactions with other co-administrated drugs, which situation is more the rule than the exception as HIV-infected patients are very frequently poly-medicated. Furthermore, hereditary alterations in metabolism exist and might be responsible, at least partially, for the inter-individual variability observed in the exposure to the drug despite a fixed-dose regimen. This raises the question about the appropriateness of a fixed dose regimen for every patient and highlights the need of identifying PK/PD predictors. This is the project thesis of Gabriel Stillemans (supervisor professors Laure Elens and Vincent Haufroid) that is focusing on the factors affecting the pharmacokinetics of Darunavir a second-generation potent protease inhibitor (PI), approved in 2008 for treatment of naïve patients. The study is entitled “Optimization of Darunavir therapy through population pharmacokinetic modeling, simulations and dosage guidelines.
Fighting bacterial resistance : what do new drugs bring to our arsenal ?
Resistance of bacteria to currently available antibiotics becomes a major problem worldwide, with untreatable infections starting to threaten patients. In this context, the group of cellular and molecular pharmacology (Françoise Van Bambeke and Marie-Paule Mingeot-Leclercq; TFAR) is evaluating new antibiotics or adjuvant therapies (inhibitors of resistance or of virulence) against multi-resistant pathogens and is also deciphering their mechanism of action. Among the new compounds investigated, some of them are antibiotics directed against innovative, unexploited targets (designed and synthesized by the group of medicinal chemistry of Raphaël Frederick) or natural substances extracted from plants used in traditional medicine (collaboration with Joëlle Quetin-Leclercq; pharmacognosy)
How to optimize antibiotic use by means of clinical pharmacy ?
Antibiotic use in the clinics can be optimized through individualized dosing in order to maximize the probability of reaching therapeutic blood levels while at the same time limiting the risks of adverse effects. In the research group on Translational Research from Experimental and Clinical Pharmacology to Treatment Optimization (TFAR), clinical pharmacists are studying antibiotic pharmacokinetics in specific patients’ populations (children, intensive care, hemodialysis) in order to provide guidance for dosing optimization based on therapeutic monitoring coupled to dosing algorithms. They also examine how to rationalize antibiotic use in specific situations (prophylaxis of surgical procedures) and look for risk factors for developing toxicities. This work is performed by PhD students working under the co-supervision of to investigators of the group (O. Dalleur, L. Elens, A. Spinewine, F. Van Bambeke).
Playing with pathogenicity and host response to tackle tolerance and resistance to antibiotics in persistent infections
Beside resistance, tolerance to antibiotics also participates to therapeutic failure. Tolerance is due to the capacity of bacteria to adopt specific lifestyles like intracellular survival or biofilm, which are poorly responsive to antibiotics. It can be explained by a lack of access of the antibiotics to the bacteria localized in these protected niches together with a switch to a dormant phenotype that is not susceptible to antibiotics. The aim of the research performed in the group of Françoise Van Bambeke (cellular and molecular pharmacology; TFAR) is precisely to elucidate why and how bacteria become tolerant to antibiotics in these specific situations and to propose and to test innovative therapeutic strategies in this context. In parallel, strategies aiming at reducing bacterial virulence and at modulating host inflammatory response are also examined.
How do gut microbes contribute to health and diseases ?
Profs Delzenne, Cani and Bindels are co-leading collaborative and interdisciplinary research projects dedicated to unravel the mechanisms linking the gut microbiota and host metabolism in several pathological contexts. Using innovative technologies, they investigate the role of specific bacteria (e.g. Akkermansia, Lactobacillus, Faecalibacterium, Bifidobacterium species), gut peptides, bacterial metabolites and gut microbiota-targeting foods and drugs in several metabolic disorders. Our ultimate goal is to offer a better understanding of the crosstalk between gut microbes and their host in physiological and pathophysiological contexts, in order to pinpoint new therapeutic targets and tools for the treatment of metabolic diseases through the modulation of the gut microbiota.
How can we efficiently deliver vaccines?
Harnessing the immune system to fight cancer is an attractive strategy. Prof V. Préat, Dr G. Vandermeulen, and their team aim at optimizing DNA vaccines to specifically treat tumors. They improve both the vaccine itself, at the molecular point of view, and the systems that allow its delivery, in particular electroporation. Their latest research exploits the properties of viral proteins which are engineered to efficiently present tumor antigens to the immune system. The project aims to provide a potent and versatile nucleic acid-based platform able to target several cancers. In parallel, Prof. R. Vanbever explores the potential of the pulmonary route for the local delivery of vaccine adjuvants.