Molecular biomarkers are valuable tools to predict the disease and determine its course. Several markers have been associated with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); Show more
Molecular biomarkers are valuable tools to predict the disease and determine its course. Several markers have been associated with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); however, none is sufficiently reliable to enable accurate diagnosis. We characterized a broad panel of serum proteins to assess disease-specific biomarker profiles and associate these findings with faecal microbiota composition in newly diagnosed IBD and IBS patients and healthy individuals. The study cohort consisted of 49 newly diagnosed treatment-naïve adult patients (13 Crohn's disease (CD), 13 ulcerative colitis (UC), and 23 IBS) and 12 healthy individuals. Inflammatory and metabolism-related serum proteins were assessed using PEA multiplex panels, while gut microbiota composition was determined by 16 s rRNA gene amplicon sequencing. Serum proteins AXIN1, TNFSF14, RNASE3, EN-RAGE, OSM, ST1A1, CA13 and NADK were identified as markers with the most promising specificity/sensitivity and predictivity between healthy and disease groups, while IL-17A and TNFRSF9 enabled differentiation between IBD and IBS patients. Increased abundance of Enterobacteriaceae was associated with protein markers significantly elevated in IBD/IBS. In contrast, depletion of beneficial taxa like Ruminococcaceae and Verucomicrobiaceae (i.e. Akkermansia muciniphila) was associated with decrease of a set of markers in diseased groups. Differences in the abundance of Turicibacteriaceae were more predictive to discern CD from UC than any of the serum proteins investigated. By using a broad panel of inflammation and metabolism-related proteins, we determined serum markers with significantly different levels in treatment-naïve IBD and IBS patients compared to healthy individuals, as well as between IBD and IBS. KEY MESSAGES : Significant changes in the levels of several serum proteins and abundances of faecal bacterial taxa between study groups were found. Increased levels of AXIN1, TNFSF14, RNASE3, EN-RAGE, OSM, ST1A1, CA13 and NADK characterize both IBD and IBS, while IL-17A and TNFRSF9 differentiate IBD from IBS. Increase of Enterobacteriaceae and depletion of beneficial taxa Ruminococcaceae and Verucomicrobiaceae (i.e. Akkermansia muciniphila) was found in IBD and IBS. Differences in Turicibacteriaceae were more predictive to discern CD from UC than any of the serum proteins investigated. Show less
Traditional transcriptomic studies often overlook the complex heterogeneity of skeletal muscle, as they typically isolate RNA from mixed muscle fibre and cell populations, resulting in an averaged tra Show more
Traditional transcriptomic studies often overlook the complex heterogeneity of skeletal muscle, as they typically isolate RNA from mixed muscle fibre and cell populations, resulting in an averaged transcriptomic profile that obscures fibre type-specific differences. This study assessed the potential of the recently developed Xenium platform for high-resolution spatial transcriptomic analysis of human skeletal muscle histological sections. Human vastus lateralis muscle samples from two individuals were analysed using the Xenium platform and Human Multi-Tissue and Cancer Panel targeting 377 genes complemented by staining of successive sections for Myosin Heavy Chain isoforms to differentiate between type 1 and type 2 muscle fibres. Manual segmentation of muscle fibres allowed accurate comparisons of transcript densities across fibre types and subcellular regions, overcoming limitations in the platform's automated segmentation. The analysis revealed higher transcript density in type 1 fibres, particularly in nuclear and perinuclear areas, and identified 191 out of 377 genes with differential expression between muscle fibres and perimysium. Genes such as PROX1, S100A1, LGR5, ACTA2, and LPL exhibited higher expression in type 1 fibres, whereas PEBP4, CAVIN1, GATM, and PVALB in type 2 fibres. We demonstrated that the Xenium platform is capable of high-resolution spatial in situ transcriptomic analysis of skeletal muscle histological sections. This study demonstrates that, with manual segmentation, the Xenium platform effectively performs fibre type-specific transcriptomic analysis, providing new insights into skeletal muscle biology. Show less