Frederik-Jan Van Schooten at the Breath Biopsy Conference 2022

[34 mins] ADVANCES IN TECHNOLOGIES IN BREATH ANALYSIS: Breath collection in animal models: an optimization and case study on abdominal sepsis

00:00 Introduction 

0:40 Talk

22:58 Q&A

Talk Abstract:

Volatile Organic Compounds (VOCs) are measured in the breath with the aim of using these compounds as the basis for non-invasive diagnostic and monitoring tools in human diseases. During the last decades, many and varying exogenous and endogenous derived VOCs have been proposed as indicators of diseased conditions. However, a clear association of these promising diagnostic VOCs with pathophysiological processes is largely unknown. Together with the lack of validations in larger studies, this hinders its adoption by clinicians and regulatory authorities, and consequently its implementation in clinical practice. To obtain biochemical backup of endogenous VOCs, animal models, along with volatiles emitted by cell and bacterial cultures, are instrumental and may lead to a better understanding of the origin and exhalation kinetics of breath VOC biomarkers. Animal studies are easier to standardize and better equipped to relate specific VOCs more directly to metabolic and pathological processes. However, long-term animal experiments are often limited by invasive breath collection methods and termination of experiments. To overcome this problem, we developed a novel device for non-invasive breath collection in mice using glass nose-only restrainers, eliminating the need of anesthetics [1]. Exhaled air is collected on desorption tubes and analyzed for VOCs by GC-Mass Spec instruments. The device has the potential to facilitate VOC research regarding disrupted metabolism and/or disease pathways.

After optimization of the sampling device, as a first attempt, we studied abdominal sepsis that might be a problem after colorectal cancer surgery because of anastomic leakage, and is a severe condition that requires early and specific antibiotic treatment. We examined in a mouse model whether VOCs in exhaled breath may have potential as early warning signs of abdominal sepsis. For this, we provoked abdominal sepsis in mice with Escherichiae Coli and Enterococcus Faecalis as inducers and sampled exhaled air at specified time points until sepsis occurs. The case study demonstrated specific breath profiles for animals that developed Escherichiae Coli-induced and Enterococcus Faecalis-induced abdominal sepsis. In addition, a time course of the development of abdominal sepsis was observed in the VOC profiles and this provides an opportunity to non-invasively detect the clinical occurrence of abdominal sepsis. However, it remains to be determined whether this finding can be translated to clinical patients undergoing colorectal surgery who are at risk for anastomotic leakage and abdominal sepsis.

Speaker Biography:

Prof Van Schooten studied Biology at the Faculty of Natural Sciences of the Free University in Amsterdam, The Netherlands, and finished with a MSci in Medical Biology in 1985. From 1985, he worked as a staff member at the Netherlands Cancer Research Institute in Amsterdam and based on the research conducted here he obtained his PhD in 1991 at Leiden University. In 1991, he moved to the Faculty of Health, Medicine and Life Sciences at Maastricht University and in 2001 became Full Professor on the chair of Genetic Toxicology.

At Maastricht University, Prof Van Schooten heads the Department of Pharmacology and Toxicology and leads the Division Respiratory & Age-related Health of the NUTRIM School of Nutrition and Translational Research in Metabolism. He has more than 35 years of senior management experience in life sciences research, academic education, heading departments and faculty management, public health policy, and valorization of science. Published over 300 papers in peer-reviewed journals, including 50 with clinical research on breath biomarker discovery and the statistical handling of breath-based data. He obtained numerous grants for research and is external reviewer of Dutch and foreign scientific programs. He teaches in Bachelor and Master educational programs in Molecular Life Sciences, and supervised(s) 50 PhD students. Member of several editorial boards, including Journal of Breath Research and he is Associate Editor of Chemosphere, Elsevier. He was member of the Dutch Health Council and its associated ad hoc committees.

Prof Van Schooten’s research is within the field of molecular epidemiology developing biomarkers as indicators of inflammation, DNA damage and repair, and genetic susceptibility for disease. The aim to better understand disease etiology and to develop opportunities for disease prevention, diagnosis and treatment. An important focus concerns the induction and prevention of chronic diseases (inflammatory diseases and carcinogenesis) focusing on inhalatory exposures (tobacco, vaping, microplastics, air pollution) or oral exposures (food processing mutagens, contaminants,supplements, microplastics), and applying both in vitro and in vivo models. His translational clinical research mainly consists applying a metabolomics approach in exhaled air through measuring volatile organic compounds (VOCs) by GC-TOF-MS for early diagnosis and monitoring therapeutic responses in inflammatory-related diseases of gut, liver and lung.

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