Biology subjects

van Mil, S.

Publications and source records attributed to van Mil, S..

3 recordsLinked to original sources

bioRxiv2025

Development of a metabolic signature of post-weaning diarrhoea in pigs

In the agricultural sector, antibiotics have been used to improve swine growth performance. This application is banned nowadays, due to increased risk of antibiotic resistance. In piglets this results in a higher prevalence of post-weaning diarrhoea, deteriorating both animal health and performance. Our goal was to find a metabolite signature separating piglets with low faecal consistency score (FCS) from piglets with normal faecal consistency and determine which pathways were enriched in this signature. By using direct infusion mass spectrometry on blood spots, we built machine learning (ML) models that aimed to differentiate between low and normal FCS. To test the general predictive capability of these models, we applied a Leave-One-Country-Out (LOCO) strategy for cross validation. Our second approach after LOCO was finding the optimal number of features to include in a feature-reduced model. To determine the order in which features were to be eliminated, we ranked them based on a combination of t-test and fold-change significance scores. Enrichment analysis using mummichog was used to gain insights into the final signature set of m/z values found using this ranking and ML models. Models trained both using all countries and leaving out specific countries from training showed a limited ability to predict FCS category. Furthermore, the LOCO results were mixed, with some countries showing a predictive signal present in the data, but others with predictive capability that was no better than random. Signature analysis using t-test and fold-change results did not result in any KEGG pathways that were enriched in this signature as compared to random. Using these methods, we could predict the FCS category to a limited degree. Although no common signature for low faecal consistency could be determined using this method, given that some countries showed more reliable LOCO results, further analysis into specifically the samples from those countries could be a valuable next step. No metabolite signature enriched in changes to KEGG pathways was found in the data using the combined t-test and fold-change analysis ranking method. We have shared the data with the community through the MetaboLights repository.

bioinformatics↗

bioRxiv2023

Dietary cystine restriction increases the proliferative capacity of the small intestine of mice

Over 88 million people are currently estimated to have adopted towards a vegan or vegetarian diet. Cysteine is a semi-essential amino acid, which availability is largely dependent on dietary intake of meat, eggs and whole grains. Vegan/vegetarian diets are therefore inherently low in cysteine concentrations. Sufficient uptake of cysteine is crucial, as it serves as substrate for protein synthesis and conversion to taurine and glutathione. In this study, we therefore investigate the effect of low dietary cystine, the oxidized derivative of cysteine, on intestinal epithelial layer function. Mice (8/group) received a high fat diet with normal or low cystine concentration for 2 weeks. We observed no changes in plasma methionine, cysteine, taurine or glutathione levels after 2 weeks. Stem cell markers as well as the proliferation marker Ki67 were increased upon cystine restriction in the small intestine. In line with this, gene set enrichment analysis indicated enrichment of Wnt signaling in the small intestine of mice on the low cystine diet, indicative of proliferative cells. Increased proliferation was absent in the colon. In the colon, dietary cystine restriction results in an increase in goblet cells, but no significant changes in the thickness of the mucus barrier or in its protective capacity. Also the microbiome was not changed upon dietary restriction. In conclusion, we show that cystine restriction for two weeks does not seem to induce any systemic effects. The increased proliferative capacity and number of goblet cells observed in the intestine may be the effect of starting epithelial damage or a reaction of the epithelium to start enlarging the absorptive capacity.

molecular biology↗

bioRxiv2019

MetaboShiny - interactive processing, analysis and identification of untargeted metabolomics data

Direct infusion untargeted metabolomics, as mass-over-charge values and intensity of ions, allows for rapid insight into a samples metabolic activity. However, analysis is often complicated by the large array of detected m/z values and the difficulty to prioritize important m/z and simultaneously annotate their putative identities. To address this challenge, we developed MetaboShiny, a novel R/RShiny-based metabolomics package featuring data analysis, database- and formula-prediction-based annotation and visualization. To demonstrate this, we reproduce and further explore a MetaboLights metabolomics bioinformatics study on lung cancer patient urine samples. MetaboShiny enables rapid and rigorous analysis and interpretation of direct infusion untargeted metabolomics data.

bioinformatics↗