**7. Metabolomics in psoriasis**

Metabolites/biochemical intermediates/end-products, unique chemical fingerprints of proteomic or cellular metabolic pathways, are viewed as keystones of life as they provide vital communication signals that are necessary to sustain life. Metabolomics, a systematic study of the global metabolite profile in a biological system, i.e., cell, tissue, organ, or organism, provides an "instantaneous snapshot"/ direct "functional readout of the physiological state", capturing the metabolic perturbations driving physiological and disease states. The metabolome, highly dynamic like transcriptome and proteome, and a rapid indicator of biological status, refer to the complete set of diverse small-molecules (<1500 Da) such as sugars, nucleotides, amino acids and lipids in any biological system.

A large number of psoriatic disease-related metabolomic studies have been carried out in the recent past to identify metabolomic biomarkers associated with psoriatic disease [95]. The majority of studies have focused on identifying a metabolic profile that can be used for diagnosis of psoriasis and/or psoriatic arthritis while others have explored correlating the metabolome with different dimensions of psoriatic disease activity to improve clinical management. A variety of biological samples including peripheral blood (whole blood, plasma, serum, peripheral blood mononuclear cells), urine, and skin tissue (uninvolved skin, psoriatic skin, and corticosteroid treated psoriatic skin) have been researched in these metabolomic studies, revealing alterations predominantly in pathways associated with lipid and amino acid metabolism. To get more meaningful information, a few study-groups have compared metabolite concentrations in different biological milieu by examining metabolomes across multiple

sample matrices. A variety of metabolites in the eicosapentaenoic, docosahexaenoic and arachidonic acid pathways are elevated in both the skin and the peripheral blood of psoriatic patients [96, 97]. Plasma and psoriatic skin choline levels correlated positively while citrulline levels across both sample matrices correlated negatively with disease activity scores [98].

A step further, Tarentini et al. integrated results of metabolomic profiling and cytokine/chemokines profiling from lesional skin and serum of psoriatic patients and identified immuno-metabolic clusters indicating biochemical pathways associated with the initial phases of psoriasis development, thus hinting at putative biomarkers of new-onset psoriasis [99].
