Targeted Assays

Bile acids are derived from cholesterol and serve an important role in emulsifying and digesting lipids. In addition, their metabolism is intimately involved with the microbiota and they have been shown to exhibit endocrine and metabolic activity via receptors like FXR and TGR5.

The Bile Acid Panel measures all of the major human and rodent primary and secondary bile acids as well as their glycine and taurine conjugates.

7-α-Hydroxy-4-cholesten-3-one (C4) is an intermediate in the biosynthesis of bile acids from cholesterol. The precursor to C4 is 7α-hydroxycholesterol which is produced from cholesterol via the hepatic enzyme, 7α-hydroxylase. 7-α-hydroxylase catalyzes the rate-limiting step in bile acid synthesis and its activity is tightly regulated via the FXR receptor. Measurement of the stable metabolite C4, a product of the next oxidative enzymatic reaction after 7-α-hydroxylase, is reflective of hepatic de-novo bile acid synthesis and FXR receptor activation. Bile acid malabsorption is associated with a variety of gastrointestinal pathologies (e. irritable bowel syndrome, ileal disease) and is characterized by elevated serum C4 levels.

Uremic toxicity is the buildup of toxic analytes that are not able to be adequately filtered by the kidneys due to kidney injury or disease. Indole metabolites of tryptophan, the tyrosine metabolite p-cresol sulfate and 4-ethylphenyl sulfate are a key group of gut microbiota-derived uremic compounds. Their formation is the result of a complex interaction between diet, gut microbiota and host. Increased production of these compounds by the gut microbiota and reduced clearance in kidney disease can lead to toxicity affecting nearly all systems in the body.

Short-chain fatty acids (SCFAs) are produced in the colon by the gut microbiota. They are the end products of anaerobic fermentation of dietary fibers and protein/peptides in the small intestine. Their formation is the result of a complex interaction between diet, gut microbiota and host. SCFAs influence the physiology of the colon serving as energy sources by host cells and the intestinal microbiota as well as participating in different host- signaling mechanisms.

Sebum is a complex mixture of lipids secreted by mature sebocytes onto the surface of skin. Sebum may have antimicrobial, photoprotection and vitamin delivery functions, and changes in the concentration and composition of sebum are related to acne and other skin disorders. Sebum is comprised of an unusual mix of lipid classes that is remarkably different in quantity and quality from lipids found in other organs. Major components are triglycerides, wax esters, squalene and free fatty acids. The fatty acid composition of the complex lipids and the free fatty acid fraction is unique to human skin. Large amounts of the unusual sapienic acid (16:1n10) as well as a variety of odd and branched chain fatty acids are present.

Trimethylamine (TMA) is a metabolite produced by certain gut bacteria from choline, betaine and carnitine found in red meat, eggs, fish and poultry. TMA is converted into TMAO in the liver and elevated plasma levels of TMAO has been linked to increased risk for major adverse cardiovascular events. Ongoing studies aim to determine if TMAO is a mediator of cardiovascular disease or a bystander in the disease process. Since specific gut bacteria play a central role in the production of TMAO, natural product therapeutics aimed at altering gut microbiota composition has gained interest.

The kynurenine pathway is a metabolic pathway leading to the production of nicotinamide adenine dinucleotide (NAD+) from the enzymatic conversion of tryptophan. Immune activation leads to the formation of kynurenine with corresponding loss of tryptophan.

The kynurenine/tryptophan ratio has been used to reflect the activity of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in cellular inflammatory response related to symptoms of depression, schizophrenia, and other neurological disease.