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Elevated long-chain to very long-chain ceramide ratios emerged as potential biomarkers linked to disease severity across IBD, PSC, and PSC-IBD. 

A study published in June 2025 issue of Scientific Reports explored the distinct roles of circulating ceramide (Cer) species and their unclear links to disease severity in individuals with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC). 

Researchers examined whether the serum levels of Cer and hexosylceramide were linked to disease severity in individuals with IBD and PSC. 

They analyzed serum levels of 8 Cer species and 5 hexosylceramide species in 93 individuals, including 16 healthy controls, 57 individuals with IBD, 7 with PSC, and 13 with PSC-IBD. Lipid quantification was performed using direct flow injection analysis coupled with a triple quadrupole mass spectrometer to determine the concentrations of each lipid species. 

The results showed that individuals with IBD had elevated levels of Cer [18:1; O2/16:0] and [18:1; O2/18:0] compared to healthy controls. The long-chain (LC) to very long-chain (LC/VLC) Cer ratio was higher in the IBD group and showed a positive correlation with C-reactive protein and fecal calprotectin. No associations were found between Cer or hexosylceramide concentrations and stool consistency, disease localization, or extra-intestinal manifestations. In individuals with PSC and those with PSC-IBD, the LC/VLC Cer ratio also increased, largely due to a reduction in VLC Cer. In the PSC-IBD group, this ratio was positively correlated with markers of cholestasis. Additionally, serum hexosylceramide [18:1; O2/16:0] and [24:1] levels were notably elevated in PSC. 

Investigators concluded that an imbalanced LC to VLC Cer ratio was linked to disease severity in IBD, PSC, and their overlap, supporting its potential as a biomarker. 

Source: nature.com/articles/s41598-025-07308-8