Metabolic Phenotyping of an Adoptive Transfer Mouse Model of Experimental Colitis and Impact of Dietary Fish Oil Intake

Abstract

Inflammatory bowel diseases are acute and chronic disabling inflammatory disorders with multiple complex etiologies that are not well-defined. Chronic intestinal inflammation has been linked to an energy-deficient state of gut epithelium with alterations in oxidative metabolism. Plasma-, urine-, stool-, and liver-specific metabonomic analyses are reported in a naïve T cell adoptive transfer (AT) experimental model of colitis, which evaluated the impact of long-chain n-3 polyunsaturated fatty acid (PUFA)-enriched diet. Metabolic profiles of AT animals and their controls under chow diet or fish oil supplementation were compared to describe the (i) consequences of inflammatory processes and (ii) the differential impact of n-3 fatty acids. Inflammation was associated with higher glycoprotein levels (related to acute-phase response) and remodeling of PUFAs. Low triglyceride levels and enhanced PUFA levels in the liver suggest activation of lipolytic pathways that could lead to the observed increase of phospholipids in the liver (including plasmalogens and sphingomyelins). In parallel, the increase in stool excretion of most amino acids may indicate a protein-losing enteropathy. Fecal content of glutamine was lower in AT mice, a feature exacerbated under fish oil intervention that may reflect a functional relationship between intestinal inflammatory status and glutamine metabolism. The decrease in Krebs cycle intermediates in urine (succinate, α-ketoglutarate) also suggests a reduction in the glutaminolytic pathway at a systemic level. Our data indicate that inflammatory status is related to this overall loss of energy homeostasis.

Effects of Dietary Plant Sterols and Stanol Esters with Low- and High-Fat Diets in Chronic and Acute Models for Experimental Colitis

“…This might explain the differences of the HFD-induced reduced inflammation we observe between the two models. There are also discrepancies in the effectiveness of dietary intervention in colitis models using other dietary lipids [ 19 ]. Inconsistent findings of the effect of omega-3 fatty acids in different colitis models demonstrate that we need to study the effects of plant sterol or stanol in more depth.…”

“…Inconsistent findings of the effect of omega-3 fatty acids in different colitis models demonstrate that we need to study the effects of plant sterol or stanol in more depth. Metabolomic analysis could help to get insights in possible molecular processes [ 19 ].…”

Urinary Metabolic Phenotyping Reveals Differences in the Metabolic Status of Healthy and Inflammatory Bowel Disease (IBD) Children in Relation to Growth and Disease Activity

“…Both NMR and MS methods generate high density data, from which meaningful biological information are recovered using multivariate data analytical approaches [17,18]. Metabonomics has already begun to contribute to the field by generating key metabolic insights [1,19,20,21]. In the context of the study of pediatric subjects, metabonomics offers a unique opportunity to capture metabolic fingerprints of an individual using minimally invasive samples, such as blood spots or urine.…”

Translational Potential of Metabolomics on Animal Models of Inflammatory Bowel Disease—A Systematic Critical Review

“…Many metabolites were found in several different sample types in both humans and animals, but not necessarily the same. For example, alanine was increased in serum [24] and feces [4,25] from humans and in colon [17] and plasma [26] from mice, but it was decreased in urine [43] and colon [35,36] in humans and serum [16] and urine [38] in animals, illustrating the differences observed for many metabolites (Supplementary Table S9). The highest similarity to human studies was observed with the acute DSS mouse model ( Supplementary Table S9).…”