Development of a Global Metabo-Lipid-Prote-omics Workflow to Compare Healthy Proximal and Distal Colonic Epithelium in Mice

A multimetabo-lipid-prote-omics workflow was developed
to characterize
the molecular interplay within proximal (PC) and distal (DC) colonic
epithelium of healthy mice. This multiomics data set lays the foundation
to better understand the two tissue types and can be used to study,
for example, colon-related diseases like colorectal cancer or inflammatory
bowel disease. First, the methyl tert-butyl ether
extraction method was optimized, so that from a single tissue biopsy
>350 reference-matched metabolites, >1850 reference-matched
lipids,
and >4500 proteins were detected by using targeted and untargeted
metabolomics, untargeted lipidomics, and proteomics. Next, each omics-data
set was analyzed individually and then merged with the additional
omics disciplines to generate a deep understanding of the underlying
complex regulatory network within the colon. Our data demonstrates,
for example, differences in mucin formation, detected on substrate
level as well as on enzyme level, and altered lipid metabolism by
the detection of phospholipases hydrolyzing sphingomyelins to ceramides.
In conclusion, the combination of the three mass spectrometry-based
omics techniques can better entangle the functional and regional differences
between PC and DC tissue compared to each single omics technique.