Biology subjects

Skurk, T.

Publications and source records attributed to Skurk, T..

5 recordsLinked to original sources

bioRxiv2024

Dietary fiber intervention modulates the formation of the cardiovascular risk factor trimethylamine-N-oxide after beef consumption

The gut-microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) has emerged as a potential risk factor for cardiovascular disease (CVD). Conversely, dietary fiber has been associated with a reduced risk of CVD and been proposed to exhibit beneficial effects on gut health. Considering these associations, we conducted an intervention study to investigate the influence of fiber supplementation on intestinal TMAO formation and its response after beef consumption. Our randomized, double blind, pilot study MEATMARK included thirteen volunteers who underwent a dietary fiber and placebo intervention over two weeks. We assessed the effect of fiber supplementation on the gut microbiota and expression of the enzyme cutC, a key enzyme for microbial TMA formation, a precursor for TMAO. We measured the TMAO response following beef consumption after the two-week intervention. We further investigated the impact of three human single nucleotide polymorphisms (SNPs) in the expression of the hepatic enzyme FMO3 on TMAO plasma levels, as this factor is responsible for the final oxidation step from TMA to TMAO. Our findings indicate that dietary fiber supplementation attenuated TMAO formation after beef intake, particularly in participants with habitual lower daily meat consumption. Furthermore, we observed a significant downregulation of cutC expression in response to the fiber intervention, suggesting a potential mechanism to reduce plasma TMAO. Considering these findings, a high fiber, low meat diet presents a promising dietary strategy for reducing this CVD risk factor. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/602621v1_ufig1.gif" ALT="Figure 1"> View larger version (77K): org.highwire.dtl.DTLVardef@1f8fd4eorg.highwire.dtl.DTLVardef@1be2baborg.highwire.dtl.DTLVardef@24fae8org.highwire.dtl.DTLVardef@1d4cac2_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2023

The gut commensal Blautia maintains colonic mucus function under low fiber consumption through short-chain fatty acid-mediated activation of Ffar2

Beneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the gut bacterial configuration and disturbs this microbe-mucus interaction, but the specific bacteria and microbial metabolites responsible for maintaining mucus function remain poorly understood. By using human-to-mouse microbiota transplantation and ex vivo analysis of colonic mucus function, our proof-of-concept study demonstrates that individuals who increase their daily dietary fiber intake can improve the capacity of their gut microbiota to prevent diet-mediated mucus defects. Mucus growth, a critical feature of intact colonic mucus, correlated with the abundance of the gut commensal Blautia, and supplementation of Blautia coccoides to mice confirmed its mucus-stimulating capacity. Mechanistically, B. coccoides stimulated mucus growth through the production of the short-chain fatty acids propionate and acetate via activation of the short-chain fatty acid receptor Ffar2, which could serve as a new target to restore mucus growth during mucus-associated lifestyle diseases.

microbiology↗

bioRxiv2023

The HuMet Repository: Watching human metabolism at work

The human metabolism constantly responds to stimuli such as food intake, fasting, exercise, and stress, triggering adaptive biochemical processes across multiple metabolic pathways. To understand the role of these processes and disruptions thereof in health and disease, detailed documentation of healthy metabolic responses is needed but still scarce on a time-resolved metabolome-wide level. Here, we present the HuMet Repository, a web-based resource for exploring dynamic metabolic responses to six physiological challenges (exercise, 36 h fasting, oral glucose and lipid loads, mixed meal, cold stress) in healthy subjects. For building this resource, we integrated existing and newly derived metabolomics data measured in blood, urine, and breath samples of 15 young healthy men at up to 56 time points during the six highly standardized challenge tests conducted over four days. The data comprise 1.1 million data points acquired on multiple platforms with temporal profiles of 2,656 metabolites from a broad range of biochemical pathways. By embedding the dataset into an interactive web application, we enable users to easily access, search, filter, analyze, and visualize the time-resolved metabolomic readouts and derived results. Users can put metabolites into their larger context by identifying metabolites with similar trajectories or by visualizing metabolites within holistic metabolic networks to pinpoint pathways of interest. In three showcases, we outline the value of the repository for gaining biological insights and generating hypotheses by analyzing the wash-out of dietary markers, the complementarity of metabolomics platforms in dynamic versus cross-sectional data, and similarities and differences in systemic metabolic responses across challenges. With its comprehensive collection of time-resolved metabolomics data, the HuMet Repository, freely accessible at https://humet.org/, is a reference for normal, healthy responses to metabolic challenges in young males. It will enable researchers with and without computational expertise, to flexibly query the data for their own research into the dynamics of human metabolism.

biochemistry↗

bioRxiv2021

Namco: A microbiome explorer

16S rRNA gene profiling is currently the most widely used technique in microbiome research and allows for studying microbial diversity, taxonomic profiling, phylogenetics, functional and network analysis. While a plethora of tools have been developed for the analysis of 16S rRNA gene data, only a few platforms offer a user-friendly interface and none comprehensively covers the whole analysis pipeline from raw data processing down to complex analysis. We introduce Namco, an R shiny application that offers a streamlined interface and serves as a one-stop solution for microbiome analysis. We demonstrate Namcos capabilities by studying the association between a rich fibre diet and the gut microbiota composition. Namco helped to prove the hypothesis that butyrate-producing bacteria are prompted by fibre-enriched intervention. Namco provides a broad range of features from raw data processing and basic statistics down to machine learning and network analysis, thus covering complex data analysis tasks that are not comprehensively covered elsewhere. Namco is freely available at https://exbio.wzw.tum.de/Namco/. Impact statementAmplicon sequencing is a key technology of microbiome research and has yielded many insights into the complexity and diversity of microbiota. To fully leverage these data, a wide range of tools have been developed for raw data processing, normalization, statistical analysis and visualization. These tools are mostly available as R packages but cannot be easily linked in an automated pipeline due to the heterogeneous characteristics of microbiome data. Instead, user-friendly tools for explorative analysis are needed to give biomedical researchers without experience in scripting languages the possibility to fully exploit their data. Several tools for microbiome data analysis have been proposed in recent years which cover a broad range of functionality but few offer a user-friendly and beginner-friendly interface while covering the entire value whole value chain from raw data processing down to complex analysis. With Namco(https://exbio.wzw.tum.de/namco/), we present a beginner-friendly one-stop solution for microbiome analysis that covers upstream analyses like raw data processing, taxonomic binning and downstream analyses like basic statistics, machine learning and network analysis, among other features.

bioinformatics↗

bioRxiv2019

Characterization of bulk phosphatidylcholine compositions in human plasma using side-chain resolving lipidomics

Kit-based assays, such as AbsoluteIDQ p150, are widely used in large cohort studies and provide a standardized method to quantify blood concentrations of phosphatidylcholines (PCs). Many disease-relevant associations of PCs were reported using this method. However, their interpretation is hampered by lack of functionally relevant information on the detailed fatty acid side chain compositions as only the total number of carbon atoms and double bonds is identified by the kit. To enable more substantiated interpretations, we characterized these PC sums using the side chain resolving Lipidyzer platform, analyzing 223 samples in parallel to the AbsoluteIDQ. Combining these datasets, we estimated the quantitative composition of PC sums and subsequently tested their replication in an independent cohort. We identified major constituents of 28 PC sums, revealing also various unexpected compositions. As an example, PC 16:0_22:5 accounted for more than 50% of the PC sum with in total 38 carbon atoms and 5 double bonds (PC aa 38:5). For 13 PC sums, we found relatively high abundances of odd-chain fatty acids. In conclusion, our study provides insights in PC compositions in human plasma, facilitating interpretation of existing epidemiological datasets and potentially enabling imputation of PC compositions for future meta-analyses of lipidomics data.

epidemiology↗