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.

Primary sclerosing cholangitis (PSC) is a serious liver disease associated with inflammatory bowel disease (IBD). Galectin-3, an inflammatory and fibrotic molecule, has elevated circulating levels in patients with chronic liver disease and inflammatory bowel disease (IBD). This study aims to clarify whether galectin-3 can differentiate between patients with IBD, PSC, and PSC-IBD. Our study measured serum galectin-3 levels in 38 healthy controls, 55 patients with IBD, and 22 patients with PSC (11 patients had underlying IBD and 11 patients did not), alongside the urinary galectin-3 of these patients and 18 controls. Serum and urinary galectin-3 levels in IBD patients were comparable to those in controls. Among IBD patients, those with high fecal calprotectin, indicating severe disease, exhibited lower serum and elevated urinary galectin-3 levels compared to those with low calprotectin levels. Serum galectin-3 levels were inversely correlated with C-reactive protein levels. PSC patients displayed higher serum and urinary galectin-3 levels than IBD patients, with the highest serum levels observed in PSC patients with coexisting IBD. There was no correlation between serum and urinary galectin-3 levels and laboratory indicators of liver injury in both IBD and PSC patients. In conclusion, this study demonstrates that serum and urinary galectin-3 levels can distinguish IBD from PSC patients, and also reveals higher serum galectin-3 levels in PSC-IBD patients compared to those with isolated PSC.

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.

Predicting responses and monitoring the severity of inflammatory bowel disease (IBD) is challenging due to a lack of specific biomarkers. This study identifies urinary hydroxyproline, a marker of collagen turnover elevated in experimental colitis, as independent of conventional biomarkers like creatinine, glomerular filtration rate, C-reactive protein, and fecal calprotectin. Among 71 IBD patients, urinary hydroxyproline levels were significantly higher compared with 36 controls, with an area under the receiver operating characteristic curve of 0.814, highlighting its potential as a diagnostic tool. No significant difference in hydroxyproline levels was observed between the 50 Crohn’s disease and 21 ulcerative colitis patients, nor was there a correlation with kidney function markers, gastrointestinal symptom severity, or stool consistency. Disease localization was not associated with urinary hydroxyproline levels. Interestingly, 14 patients with primary sclerosing cholangitis and IBD also exhibited elevated urinary hydroxyproline levels, comparable to IBD patients but higher than healthy controls. This underscores the role of urinary hydroxyproline as an independent biomarker for IBD diagnosis, without association with disease severity or established markers like fecal calprotectin.

Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy controls. To our knowledge, the correlation between serum LPC species levels and measures of inflammation, as well as their potential as markers for monitoring IBD activity, has not yet been investigated. Methods: Thirteen LPC species, varying in acyl chain length and number of double bonds, were measured in the serum of 16 controls and the serum of 57 patients with IBD. Associations with C-reactive protein (CRP) and fecal calprotectin levels as markers of IBD severity were assessed. Results: Serum levels of LPC species did not differ between the healthy controls and the entire patient cohort. In patients with IBD, serum levels of LPC 16:1, 18:0, 18:3, 20:3, and 20:5, as well as total LPC concentrations, showed inverse correlations with both CRP and fecal calprotectin levels, indicating an association with inflammatory activity. Nine LPC species were significantly reduced in patients with high fecal calprotectin compared to those with low values. LPC species with 22 carbon atoms and 4 to 6 double bonds were not related to disease activity. Stool consistency and gastrointestinal symptoms did not influence serum LPC profiles. Corticosteroid treatment was associated with lower serum LPC 20:3 and 22:5 levels, while mesalazine, anti-TNF, and anti-IL-12/23 therapies had no significant impact on LPC concentrations. There was a strong positive correlation between LPC species containing 15 to 18 carbon atoms and serum cholesterol, triglycerides, and phosphatidylcholine levels. However, there was no correlation with markers of liver disease. Conclusions: Shorter-chain LPC species are reduced in patients with active IBD and reflect underlying hypolipidemia. While these lipid alterations provide insight into IBD-associated metabolic changes, they appear unsuitable as diagnostic or disease monitoring biomarkers.

Background/Objectives: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum cholesterol levels and inflammation, both of which are dysregulated in inflammatory bowel disease (IBD). Free cholesterol (FC) and the various types of cholesteryl ester (CE) have different functions in the body. However, it is not yet known whether these lipids undergo parallel changes in male and female patients with active IBD, nor whether PCSK9 correlates with these lipids and disease severity in either sex. The present study measured the serum levels of PCSK9, FC, and 15 CE species in IBD patients, focusing on the associations of these molecules with sex, each other, and with disease severity. Methods: The serum PCSK9 levels of 80 IBD patients (42 males and 38 females) and 24 controls (12 males and 12 females) were measured by enzyme-linked immunosorbent assay. In addition, FC and 15 CE species levels of 53 randomly selected IBD patients and 16 controls were determined by direct flow injection analysis (FIA) using a high-resolution hybrid quadrupole-orbitrap mass spectrometer (FIA-FTMS). Results: Serum PCSK9 levels in controls and IBD patients were comparable and did not correlate with disease severity in IBD patients. There was no discernible difference in serum PCSK9, FC, and CE levels between patients with Crohn’s disease (CD) and those with ulcerative colitis (UC). FC and almost all CE species decreased in male patients with active IBD but were not related to disease severity in the female patients. The decrease in different CE species in male IBD patients with diarrhea compared to those with normal stool consistency appears to be related to IBD severity. Bile acids regulate serum cholesterol levels, and FC and CE levels were positively correlated with fecal levels of secondary bile acids in the patients with UC but not CD. This association also existed in male UC patients and could not be evaluated in women due to the small sample size. Conclusions: In active IBD, a reduction in FC and almost all CE species was observed only in males, while serum PCSK9 levels remained within normal ranges in both sexes. It can be hypothesized that blocking PCSK9 may further reduce serum cholesterol levels, which may have adverse effects in male patients with active IBD.