Past, Present, and Future of Metabolomic Studies in Feline Chronic Enteropathy

Omics research encompasses multiple biological layers, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, all of which shape an organism’s phenotype.

Metabolomics refers to the comprehensive analysis of metabolites - small molecules produced as intermediates or end products of metabolic pathways. The metabolome represents the complete set of metabolites within a biological sample, reflecting interactions at the cellular, organ, or organismal level.

Metabolomic approaches include untargeted and targeted strategies. Untargeted metabolomics can identify thousands of metabolites without prior knowledge, aiding in novel biomarker discovery. These experiments are considered hypothesis-generating. However, they provide only relative quantification due to the absence of reference standards. Targeted metabolomics, in contrast, focuses on known metabolites, allowing for absolute quantification and validation of prior findings but lacking exploratory potential for new biomarkers.

Several metabolomic studies in feline chronic enteropathy (CE) have identified novel biomarker candidates with potential diagnostic, prognostic, or therapeutic relevance. Key metabolites of interest include amino acids, vitamins (A, B, D, E), tryptophan and its derivatives, sphingolipids, and arachidonic acid.

Tryptophan and its microbial indole catabolites (MICTs) serve as anti-inflammatory mediators essential for intestinal homeostasis. Cats with CE show reduced serum levels of tryptophan and MICTs, which regulate immune functions and enhance mucosal integrity via aryl-hydrocarbon (AhR) and pregnane-X (PXR) receptors. Dysbiosis-driven depletion of MICTs may perpetuate mucosal inflammation and increase intestinal permeability.

Certain urinary metabolites have shown predictive value in identifying diet-responsive CE cases. However, even when clinical disease improves, metabolic alterations persist, mirroring findings in other species with inflammatory bowel disease. The prognostic significance of these persistent changes remains unclear.

While feline CE shares metabolic disturbances with other species, identified markers lack specificity for distinguishing CE subtypes (e.g., food-responsive, IBD, low-grade intestinal T-cell lymphoma). Today, no definitive diagnostic biomarkers exist, but several promising candidates warrant further investigation, including potential therapeutic targets.