History & Evolution 2007: atmospheric fingerprinting of pinene enantiomers | 2010: pinenes considered as renewable alternative to fuel | 2014: engineering of pinene-producing E. coli. As one of the metabolites responsible for the smell of conifers (Schreiner et al. 2018), alpha-pinene is a fitting choice for our festive Metabolite of the month. This chiral molecule has two enantiomers that are found in varying proportions in different plants, as does its isomer, beta-pinene (Stephanou 2007). Pinenes are unsaturated monoterpenes characterized by two rings fused to each other, making them qu ..read more

In our recent white paper, “Chronic diseases have a common origin”, we argue that many chronic diseases share key components in their pathophysiology. Notably, non-alcoholic fatty liver disease (NAFLD) is not only prevalent in many of those diseases, but also contributes to their development. This suggests that treating NAFLD could be an effective chemopreventive strategy for those diseases. NAFLD, characterized by a build-up of fat in the liver. It is generally considered a fairly benign disorder with little impact on health outcomes or quality of life in the short term. However, it is clearl ..read more

PubMed alerts are a great way to stay in the loop with the latest research developments in metabolomics and other -omics technologies. Recently, I was thrilled to discover a new paper on investigative toxicology that mentioned metabolomics. I fully expected it to talk glowingly about the potential of metabolomics to transform toxicology. However, the publication presented more of a mixed bag. Based on surveys with toxicologists in big pharma companies in 2015 and 2020, the authors found wide-ranging perceptions of the potential impact of metabolomics: in 2020, more than one in five respondents ..read more

How metabolomics can help to reduce costs in drug development The pharmaceutical industry is one of the largest sectors of the global economy, creating drug revenues of more than $1,000 billion in 2020 alone (Mullard 2022). Research and development (R&D) investments range from $0.9 billion to $2.8 billion for each new drug, with costs expected to rise over time (Simoens et al. 2021). The high costs of failure throughout the drug development process are a significant issue, especially given the extremely low approval rate: only 9% in phase 1 and just 46% even in phase 3 clinical trials (Fog ..read more

Identification of biomarkers to diagnose diseases and find adverse drug reactions by metabolomics A common problem with today’s pharmaceutical therapies is that the patient´s reaction to a drug is often unpredictable. They may respond poorly or experience adverse effects. Precision medicine aims to pinpoint the drug with the greatest therapeutic benefit and fewest side effects for an individual patient. One route to precision medicine is through the metabolome. It reflects all biochemical processes in an organism, from the genomic level to the proteomic level, plus environmental factors. This ..read more

Association of proton pump inhibitor use with endothelial function and metabolites of the nitric oxide pathway: A cross-sectional study Long-term intake of proton pump inhibitors (PPIs) has been associated with elevated risk of cardiovascular events. Nevertheless, they are still widely used to treat increased gastric-acid production, even without medical supervision. Demonstrating and understanding a causal link between PPIs and cardiovascular risk could help to inform regulatory decisions around the safe use of PPIs in future. It has been suggested that PPIs block the enzyme activity of dime ..read more

Mitochondrial Regulation of the 26S Proteasome The more we understand about cell biology, the more we can improve pharmacological treatments. In this study, researchers from several German institutions investigated the link between mitochondrial respiration and proteasomal degradation mechanisms, with important implications for cancer drugs. Applying state-of-the-art molecular biology techniques including phosphoproteomics and metabolomics, these findings demonstrate the role of aspartate and pyruvate at the crossroads of these molecular pathways. Mitochondrial mutations in respiratory complex ..read more

Why do we need to understand the role of metabolism? It’s well known that only 20–30 % of patients experience a long-term benefit from immunotherapy, but the high rate of adverse events in immunotherapies is also a matter of intense research and scientific debate. Biomarkers that can stratify patients and identify whether they are at risk for severe toxicities are an important medical need. Here, I make the case for metabolomics as a tool for discovering such biomarkers. Earlier this month, Eschweiler and colleagues reported on a failed phase II trial for a phosphoinositide 3-kinase delta (PI3 ..read more

Non-response, loss of response and the need for stratification Resistance to available drug therapies represents a major problem in pharmaceutical therapy. The issue affects a broad field of indications including (but not limited to) diabetes, depression and multiple sclerosis (Schork 2015). Non-response is not just an issue in clinical care, but is also a major obstacle in clinical trials for new pharmaceuticals, and may help explain why 50% to 80% of clinical development programs are discontinued at each stage of clinical trial (Pammolli et al. 2020). In some disease groups, such as neurodeg ..read more

Elucidating the relations between gut bacterial composition and the plasma and fecal metabolomes of antibiotic treated wistar rats The gut microbiome influences many key functions within an organism. When a drug is administered, this can have a substantial impact not only on the individual’s health status and the immune system, but on the gut bacterial community in their microbiome. Antibiotics result in particularly significant alterations in the composition of the gut microbiome. In order to better understand the correlation between antibiotics, the microbiome, and the fecal or plasma metabo ..read more