Reply to Letter to the Editor of Dr. Sitkin et al., Regarding “Altered Sphingolipid Metabolism and its Interaction With the Intestinal Microbiome is Another Key to the Pathogenesis of Inflammatory Bowel Disease”

Extract

We thank Dr. Sitkin and colleagues for the knowledgeable comments on our article “Untargeted Metabolomics and Inflammatory Markers Profiling in Children With Crohn's Disease and Ulcerative Colitis—A Preliminary Study.” We appreciate their interest in our study, which has for the first time shown significant alteration of lactosylceramide 18:0/16:0 (LacCer 18:0/16:0) in the serum of children with inflammatory bowel disease (IBD), especially with Crohn's disease (CD). We agree that the current results indicating the involvement of LacCer in the mechanism of inflammation constitute an important point for future studies on the pathogenesis of IBD.^{1, 2} We have read carefully the authors' proposed points for future investigations, concerning sphingolipids and ceramides, to discover the metabolic pathways involved in IBD. Promising results were obtained by Bazarganipour et al., showing the increased concentrations of C16:0- and C24:0-lactosyl-ceramide (LacCer) in inflamed colon tissue of adult patients with ulcerative colitis in comparison with control tissue; however, no difference in LacCer level was found in blood between groups, probably due to an anti-inflammatory therapy reported in the study group, which could have affected the results.³ The proper selection of the study group for metabolite determination is extremely important. Recent discoveries in lipidomic and metabolomic profiling have provided opportunities to determine the metabolic pathways of IBD; however, due to the high genetic and phenotypic heterogeneity of IBD, we should try to integrate the achievements gained so far from all “omics” strategies (metabolomics, lipidomics, proteomics, transcriptomics, and genomics) to elucidate the cellular and metabolic processes related to disease etiology, diagnosis, treatment, and prevention.