Arachidonic acid levels are elevated in the colonic mucosa of patients with inflammatory bowel disease (IBD). Fecal metabolites are emerging as valuable diagnostic tools for IBD. This study aimed to investigate associations between 31 fecal fatty acids, including arachidonic acid, to identify potential correlations with disease severity. Among the 31 fatty acids analyzed in feces, dihomo-γ-linolenic acid, arachidonic acid, and adrenic acid were significantly increased in patients with IBD compared to controls. In contrast, levels of linoleic acid and γ-linolenic acid, the precursors of arachidonic acid, were similar between both groups. No significant differences in fatty acid levels were observed between patients with Crohn’s disease and ulcerative colitis. Arachidonic acid and adrenic acid levels positively correlated with fecal calprotectin, a clinically established marker of IBD severity, but showed no association with stool consistency or the Gastrointestinal Symptom Rating Scale. This suggests that these fatty acids are linked to disease severity rather than disease-related symptoms. Current IBD-specific medications had no significant impact on the fecal levels of any of the 31 fatty acids. In summary, this study demonstrates elevated fecal levels of dihomo-γ-linolenic acid, arachidonic acid, and adrenic acid in IBD patients. Normal levels of precursor fatty acids suggest that impaired downstream metabolism may contribute to the accumulation of these n-6 polyunsaturated fatty acids.

Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100 calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation. The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during 2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in 63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell counts. While C-reactive protein and procalcitonin are established inflammation markers, they did not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12 levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation. Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic indicator for bacterial and viral infections.

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic immune-mediated pathology associated with the dysregulation of lipid metabolism. The administration of nervonic acid, a very long-chain fatty acid, has been shown to improve colonic inflammation in a mouse model of colitis. Our study aimed to quantify fecal levels of nervonic acid, as well as the very long-chain fatty acids, lignoceric acid, and pentacosanoic acid, to identify associations with IBD activity. Methods: Stool samples were collected from 62 patients with IBD and 17 healthy controls. Nervonic acid, lignoceric acid, and pentacosanoic acid were quantified by gas chromatography coupled with mass spectrometry (GC-MS). Lipid levels, normalized to the dry weight of fecal homogenates, were used for calculations. Results: Patients with IBD exhibited elevated fecal nervonic acid levels compared to healthy controls, with no significant differences observed between ulcerative colitis and Crohn’s disease. A fecal nervonic acid concentration of 0.49 µmol/g distinguished IBD patients from controls, achieving a sensitivity of 71% and a specificity of 82%. Fecal nervonic acid levels showed a positive correlation with both C-reactive protein and fecal calprotectin and increased proportionally with rising fecal calprotectin levels. IBD patients treated with corticosteroids or interleukin-12/23 antibodies had higher levels of fecal nervonic acid than those in other therapies, with no difference in serum C-reactive protein and calprotectin levels between these groups. Conclusions: In summary, this analysis indicates that fecal nervonic acid may emerge as a novel specific biomarker for IBD diagnosis and disease monitoring.

Background and Aims: The K + channel KCNN4 is involved in many inflammatory diseases. Previous work has shown that this channel is involved in epithelial ion transport and intestinal restitution. In inflammatory bowel diseases (IBD) a defective epithelial barrier can lead to typical symptoms like secretory diarrhea and the formation of intestinal ulcers. We compared surgical samples from patients with IBD, diverticulitis and controls without inflammation to determine the potential role of KCNN4 as a diagnostic marker and/or therapeutic target. Methods: mRNA-levels of KCNN4 and a control K + channel were determined in intestinal epithelial cells (IEC) from patients with IBD, diverticulitis and controls. In addition, we performed a Western blot analysis of KCNN4 and a respective control K + channel in IEC from patients with IBD. Furthermore, we determined epithelial barrier integrity by measuring the flux of fluorescent-labeled dextran beads across a cell monolayer upon incubation with interferon-γ. Results: KCNN4 mRNA and protein levels were elevated in IEC from patients with Crohn`s disease (CD) and ulcerative colitis (UC). Of note, KCNN4 was not elevated in non-IBD intestinal inflammatory conditions e.g. diverticulitis. Of clinical relevance, pharmacological KCNN4 channel openers stabilized epithelial barrier function in vitro. Thus, KCNN4 may have a protective role in IBD and constitute a therapeutic target. Conclusions: Our data demonstrate elevated KCNN4 both at mRNA and protein level in IEC specifically from patients with IBD. Therefore, we conclude that KCNN4 could be used as a novel marker for IBD, especially for the establishment of initial diagnosis. Of therapeutic consequence, we show that pharmacological KCNN4 openers stabilize the epithelial barrier. Thus, KCNN4 might be a novel target to diagnose and treat IBD.

Bacterial and fungal superinfections are common in COVID-19, and early diagnosis can enable timely intervention. Serum calprotectin levels increase with bacterial, fungal, and viral infections. This study evaluated serum calprotectin as a diagnostic and prognostic tool for microbial superinfections in COVID-19. Serum samples from adult patients with moderate and severe COVID-19 were collected during hospitalization from 2020 to 2024. Calprotectin levels were measured using an enzyme-linked immunosorbent assay in 63 patients with moderate COVID-19, 60 patients with severe COVID-19, and 34 healthy individuals. Calprotectin serum levels were elevated in patients with moderate COVID-19 compared with controls, and these levels were further increased in the severe cases. Patients with severe COVID-19 and vancomycin-resistant enterococci (VRE) bacteremia had elevated calprotectin levels, but their C-reactive protein and procalcitonin levels were not increased. Fungal superinfections and herpes simplex virus reactivation did not change the calprotectin levels. A calprotectin concentration of 31.29 µg/mL can be used to diagnose VRE bloodstream infection with 60% sensitivity and 96% specificity. These data suggest that serum calprotectin may be a promising biomarker for the early detection of VRE bloodstream infections in patients with COVID-19.

Presepsin, a cleaved peptide of soluble CD14, may become a promising biomarker for assessing disease severity and mortality in coronavirus disease 2019 (COVID-19). Patients with severe COVID-19 frequently develop bacterial and fungal superinfections, as well as herpes simplex virus-1 (HSV-1) reactivation, which may exacerbate disease progression. This study aimed to evaluate the impact of concomitant infections on serum presepsin levels. Serum presepsin levels were measured using an enzyme-linked immunosorbent assay (ELISA) in 63 patients with moderate COVID-19, 60 patients with severe disease, and 49 healthy controls. Correlations with procalcitonin and the presence of superinfections or HSV-1 reactivation were assessed. Consistent with previous studies, serum presepsin levels were the highest in patients with severe COVID-19 (p = 0.002 compared to patients with moderate disease). Within this group, non-survivors exhibited significantly elevated presepsin levels (p = 0.027). A positive correlation between presepsin and procalcitonin was observed in both moderate and severe COVID-19 cases. Patients with bacterial or fungal superinfections showed presepsin levels comparable to those without secondary infections. However, presepsin levels were markedly elevated in patients with HSV-1 reactivation (p = 0.002). After excluding patients with HSV-1 reactivation, presepsin levels no longer differed between moderate and severe COVID-19 cases, though they remained higher than in healthy controls (p < 0.001 for both comparisons). In conclusion, these findings suggest that elevated serum presepsin levels in severe COVID-19 are primarily driven by HSV-1 reactivation rather than bacterial or fungal superinfections.