Within Microbiome Research for Precision Medicine, we apply beyond state-of-the-art techniques to understand host-drug-microbiome interactions
Projects in this research area address acute and chronic pathophysiological processes in different disease areas by integrating metabolic, hormonal, inflammatory and infectious disease aspects in an interdisciplinary approach.
Within the last 15-20 years, a strong interaction between diseases, therapeutics and the human gut microbiome has crystallized whereby several acute and chronic diseases can cause (or can be caused) by disturbances of the gut microbiome, known as dysbiosis. Therapeutics, such as drugs or nutritional supplements, can affect the composition and function of the microbiome both positively and negatively. Specifically, therapeutics can be modulated, activated, inhibited or metabolized by bacteria in the gut which, ultimately, determines their efficacy and safety.
THE MICROBIOME RESEARCH LIFECYCLE
We propose a microbiome research lifecycle which begins with the translation of a clinical problem into an actionable research question that can be answered using clinical data, advanced biomarker identification or assessment (from human samples) and our novel patient-derived microbiome modulation platform which serves as an in vitro model. This process is supported by an extensive biological and technological methodological repertoire which is supplied by CBmed core technologies. The results achieved here will then serve as the basis of rational clinical interventions.
UNDERSTANDING DRUG-DISEASE-MICROBIOME INTERACTION FOR A PERSONALIZED MEDICINE APPROACH
It has become evident in medicine over the past few years that the composition and function of our gut microbiome is important for our health and that drugs have an enormous impact on its composition and function. Indeed, most orally ingested substances including foodstuffs, supplements and drugs will, at some stage, of their passage through the human body encounter the intestinal microbiome. This microbiome with its several hundred bacterial species exerts an impact on the metabolism of drugs and can, thereby, determine the success or failure (side effects) of drug therapies.
DRUGS MODULATE BUGS – BUGS MODULATE DRUGS
Herein, we aim to disentangle the interactive relationships that exist between therapeutics and the human gut microbiome to understand the consequences of dysbiosis on human health and disease. Armed with these novel insights, the development of evidence-driven microbiome modulation strategies designed to either improve the efficacy of therapeutics, prevent microbiome related side effects of drugs and treat diseases becomes possible.
COVID-19 and CBmed: Success out of a difficult situation
When the COVID-19 pandemic hit Austria severely in March of 2020, CBmed was able to quickly adapt to the situation due to its sound financial performance since its inception. Remarkably, in addition to all existing projects remaining successfully and punctually managed, CBmed took concrete steps towards investing in COVID-19 related research to provide urgently needed insights and knowledge to the scientific community and public.
Two research projects related to COVID-19 and the gut microbiome were started. In addition, a project to identify a biomarker of disease severity from routine hospital datasets was launched. We developed a simple point-based score to predict outcomes with a defined number of easily available routine patients´ data (age, oxygen saturation, C-reactive protein and creatinine)- work which was published in the Journal of Hepatology in September 2021. The score has also been validated in a large dataset from the second and third waves of the COVID-19 pandemic.
Method to Determine the State of the Humoral Immune System in Patients with Liver Disease
Bacterial infections are common in liver cirrhosis. They are not easily detected, which can lead to the development of serious complications and even death. There are no routine tests available to predict susceptibility.
A reliable, easy-to-assess, and functional biomarker with the possibility of fully automated handling capable of identifying patients at risk for developing infections has been developed. This biomarker is based on the cell-free (humoral) immune response of the body that can detect and kill pathogens. It utilises the growth tendencies of a specific strain of bacteria in human serum to predict the outcome of a patient. AGRA (Acellular growth retardation ability) predicts the occurence of severe infections in patients with liver cirrhosis, accurately identifies patients at risk of infections, and tracks treatment success (EP17181908.9).
Biomarkers for Clinical Decision Support in Intensive Care
In intensive care, cumulative fluid balance may serve as a biomarker for critical illness. The Medical University of Graz and B. Braun Melsungen AG have collaborated on the development of an in-silico model of intensive care patients’ fluid balance. The model can describe the patients’ behaviour on fluid management over time, and moreover provides a prediction of their response throughout their stay in the intensive care unit. A patent application was filed in 2018 preparing the model for translation into clinical applicability.
Electrochemical Biomarker Detection in Common Metabolic Disorders
The aim of the project was to develop an electrochemical detection system for urine biomarkers, e.g. C-peptide, widely used for diabetes patients and pregnant women. Basic properties of the detection system from corrosion aspects to voltammetry results were established and optimised together with the industry partner. Proof of principle measurements have shown the detection capabilities using chip-based immunoassay at different protein concentrations. A prototype was successfully designed and included urinary collection and detection. Further technological developments are planned and promising biomarkers in urine, including candidates for clinical purposes and for electrochemical detection, have been identified for future applications.
CBmed projects aim to develop easily applicable, targeted, minimally invasive biomarkers for better diagnosis, better therapy monitoring and a more personalized treatment of patients.
Scientific Lead Microbiome Research for Precision Medicine