Multiplatform serum metabolic phenotyping combined with pathway mapping to identify biochemical differences in smokers

Aim: Determining perturbed biochemical functions associated with tobacco smoking should be helpful for establishing causal relationships between exposure and adverse events. Results: A multiplatform comparison of serum of smokers (n = 55) and never-smokers (n = 57) using nuclear magnetic resonance spectroscopy, UPLC–MS and statistical modeling revealed clustering of the classes, distinguished by metabolic biomarkers. The identified metabolites were subjected to metabolic pathway enrichment, modeling adverse biological events using available databases. Perturbation of metabolites involved in chronic obstructive pulmonary disease, cardiovascular diseases and cancer were identified and discussed. Conclusion: Combining multiplatform metabolic phenotyping with knowledge-based mapping gives mechanistic insights into disease development, which can be applied to next-generation tobacco and nicotine products for comparative risk assessment

The microbial-mammalian metabolic axis: a critical symbiotic relationship

PURPOSE OF REVIEW: The microbial-mammalian symbiosis plays a critical role in metabolic health. Microbial metabolites emerge as key messengers in the complex communication between the gut microbiota and their host. These chemical signals are mainly derived from nutritional precursors, which also are in turn also able to modify gut microbiota population. Recent advances in the characterization of the gut microbiome and the mechanisms involved in this symbiosis allow the development of nutritional interventions. This review covers the latest findings on the microbial-mammalian metabolic axis as a critical symbiotic relationship particularly relevant to clinical nutrition. RECENT FINDINGS: The modulation of host metabolism by metabolites derived from the gut microbiota highlights the importance of gut microbiota in disease prevention and causation. The composition of microbial populations in our gut ecosystem is a critical pathophysiological factor, mainly regulated by diet, but also by the host’s characteristics (e.g. genetics, circadian clock, immune system, age). Tailored interventions, including dietary changes, the use of antibiotics, prebiotic and probiotic supplementation and faecal transplantation are promising strategies to manipulate microbial ecology. SUMMARY: The microbiota is now considered as an easily reachable target to prevent and treat related diseases. Recent findings in both mechanisms of its interactions with host metabolism and in strategies to modify gut microbiota will allow us to develop more effective treatments especially in metabolic diseases

Comparison of four 31P single-voxel MRS sequences in the human brain at 9.4 T

Purpose: In this study, different single-voxel localization sequences were implemented and systematically compared for the first time for phosphorous MRS (31 P-MRS) in the human brain at 9.4 T. Methods: Two multishot sequences, image-selected in vivo spectroscopy (ISIS) and a conventional slice-selective excitation combined with localization by adiabatic selective refocusing (semiLASER) variant of the spin-echo full intensity-acquired localized spectroscopy (SPECIAL-semiLASER), and two single-shot sequences, semiLASER and stimulated echo acquisition mode (STEAM), were implemented and optimized for 31 P-MRS in the human brain at 9.4 T. Pulses and coil setup were optimized, localization accuracy was tested in phantom experiments, and absolute SNR of the sequences was compared in vivo. The SNR per unit time (SNR/t) was derived and compared for all four sequences and verified experimentally for ISIS in two different voxel sizes (3 × 3 × 3 cm3 , 5 × 5 × 5 cm3 , 10-minute measurement time). Metabolite signals obtained with ISIS were quantified. The possible spectral quality in vivo acquired in clinically feasible time (3:30 minutes, 3 × 3 × 3 cm3 ) was explored for two different coil setups. Results: All evaluated sequences performed with good localization accuracy in phantom experiments and provided well-resolved spectra in vivo. However, ISIS has the lowest chemical shift displacement error, the best localization accuracy, the highest SNR/t for most metabolites, provides metabolite concentrations comparable to literature values, and is the only one of the sequences that allows for the detection of the whole 31 P spectrum, including β-adenosine triphosphate, with the used setup. The SNR/t of STEAM is comparable to the SNR/t of ISIS. The semiLASER and SPECIAL-semiLASER sequences provide good results for metabolites with long T2 . Conclusion: At 9.4 T, high-quality single-voxel localized 31 P-MRS can be performed in the human brain with different localization methods, each with inherent characteristics suitable for different research issues

Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease

Aims: To characterise serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). Methods and Results: We used untargeted one-dimensional (1D) serum metabolic profiling by proton (1H) nuclear magnetic resonance (NMR) spectroscopy among 3,867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3,569 participants from the Rotterdam and LOLIPOP Studies. Atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-media thickness (IMT). We used multivariable linear regression to evaluate associations between NMR features and atherosclerosis accounting for multiplicity of comparisons. We then examined associations between metabolites associated with atherosclerosis and incident CVD available in MESA and Rotterdam and explored molecular networks through bioinformatics analyses. Overall, 30 NMR measured metabolites were associated with CAC and/or IMT, P =1.3x10-14 to 6.5x10-6 (discovery), P =4.2x10-14 to 4.4x10-2 (replication). These associations were substantially attenuated after adjustment for conventional cardiovascular risk factors. Metabolites associated with atherosclerosis revealed disturbances in lipid and carbohydrate metabolism, branched-chain and aromatic amino acid metabolism, as well as oxidative stress and inflammatory pathways. Analyses of incident CVD events showed inverse associations with creatine, creatinine and phenylalanine, and direct associations with mannose, acetaminophen-glucuronide and lactate as well as apolipoprotein B (P <0.05). Conclusion: Metabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclerosis