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P009 Lipid biomarkers to diagnose Crohn’s disease using metabonomic profiling approach in serum and faeces.

N. S. Ding*1, 2, M. Sarafian1, 2, R. Misra1, P. Hendy1, L. Penez1, E. Holmes2, A. Hart1

1St Mark’s Hospital, IBD, London, United Kingdom, 2Imperial College London, Department of Surgery and Cancer, London, United Kingdom

Background

Inflammatory bowel disease (IBD) is influenced by environmental and genetic factors that alter the gut microbiota. The human gut microbiota is involved in the maintenance of its host physiological functions and imbalance in the microbial population and its metabolic signatures may lead to disease activity and phenotype. We investigate the variations occurring in lipid metabolism between Crohn’s disease (CD) vs controls in serum and faeces by profiling using a metabonomic approach.1

Methods

Serum and faeces were collected from moderate-to-severe Crohn’s disease patients before commencement of anti-TNF.

Sample preparation: Protein precipitation with isopropanol was implemented on serum and faeces samples and prepared by biphasic extraction.

Lipid profiling: The method was performed on Waters Acquity UPLCTM combined with Waters Q-Tof PremierTM mass spectrometer.2

Data processing: OPLS-DA was carried out on the XCMS extracted intensities using SIMCA P+v13 and Matlab.

Lipids annotation was derived by searching m/z against online databases (METLIN, Lipidmaps and HMDB).

Results

Multivariate analyses between healthy and CD patients were performed to characterise lipid profile differences. Significant separation was observed in both serum and faeces between the 2 groups (Figure 1). Lipid metabolism is affected in CD patients compared with healthy controls.

Figure 1. OPLS-DA models of lipid profiles from serum and faeces samples of healthy and CD patients.

Correlation analysis showed that several triglyceride (TG) species were significantly associated with CD. TGs with medium-to-long chain fatty acid length and with saturations were identified at increased levels in CD patients (Figure 2). TGs with saturated fatty acids were prominent in faeces compare to serum. Moreover, TGs found in faeces were in higher concentration than in serum.

Figure 2. Biomarkers identified from correlation of lipid profiles of healthy vs CD in serum and faeces.

Conclusion

Our metabonomic study showed profound variations in both serum and faeces of CD patients. These results highlight the association between the gut microbiota and mucosal barrier function that has downstream effect on lipid metabolism and inflammation in IBD. This metabonomic approach offers potential insights into the pathophysiology and diagnosis of CD. Larger sample size with long-term lipid profiles is needed to validate the underlying mechanisms in IBD.

References

[1] Nicholson JK, Lindon JC, Holmes E. ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 1999;29(11):1181–89.

[2] Isaac G, Mc Donald S, Astaritra G. (2011), Lipid separation using UPLC with charged surface hybrid technology.