4OH-Phenylpropionic Acid

Phenylacetic acid (PAA) and phenylpropionic acid (PPA) are products of phenylalanine metabolism caused by intestinal bacteria. High levels of PAA or PPA in urine may result from the dysbiosis of intestinal flora or the decreased metabolism of phenylalanine, such as phenylketonuria (PKU). PAA is also a metabolite of 2-phenylethylamine, and low levels of PAA in urine are considered as a marker of depression. Urinary 4-hydroxybenzoic acid (4-HBA) and 4-hydroxyphenylacetic acid (4-HPAA) represent a considerable percentage of tyrosine intake. 4-HBA is one of the major catechin metabolites after the intake of green tea infusions. In addition, 4-HPAA has been found to be useful in screening for small bowel diseases associated with anaerobic bacterial overgrowth.

3-hydroxyphenylpropionic acid (3-HPPA) is a major metabolite of ingested proanthocyanidins and chlorogenic acid caused by colonic bacteria. High levels of 3-HPPA may indicate the increased intestinal bacterial metabolism of dietary polyphenols. 3,4-dihydroxyphenyl propionic acid (3,4-DHPPA) is produced from dietary quinolones, such as naringin, by various clostridial species, and elevated levels of 3,4-DHPPA may imply Clostridium overgrowth. 3-Indoleacetic acid (IAA) is a breakdown product of tryptophan metabolism produced by the action of gut bacteria, such as Bifidobacterium and Bacteroides. IAA frequently occurs at low levels in urine and has been found in elevated levels in urine of patients with phenylketonuria or diet change. Creatinine is usually produced at a fairly constant rate by muscle tissues and is applied to compensate for the different rates of metabolism between individuals. The kidney has the capacity to regulate amount of fluid within the body, hence the urinary concentration of any compound is dependent on the compound excretion rate and the urinary flow rate. The most common normalization method that urinary creatinine is used for is to adjust for quantitation of urine analyte.

Dihydroxyphenylpropionic Acid (DHPPA), also known as 3,4 dihydroxyphenylpropionic acid, is a byproduct of the fermentation of dietary phenols by several bacteria, including some Clostridia spp. and others. Although once thought to identify the presence of specific dysbiotic bacteria, ongoing research suggests there are several bacterial species potentially involved.

Elevated DHPPA levels may reflect dietary intake of polyphenols. They may also suggest dysbiosis or bacterial overgrowth, increasing dietary polyphenol conversion. 3-Hydroxyphenylacetic Acid and 4-Hydroxyphenylacetic Acid 3-Hydroxyphenylacetic acid and 4-hydroxyphenylacetic acid are produced by the bacterial fermentation of amino acids, much like IAA.

Amino acids that are not digested and absorbed can be metabolized by bacteria in the gut to form these organic acids. Clinicians often use these markers to reflect protein malabsorption or dysbiosis. However, dietary intake of polyphenols such as wine, grapes, green tea, and grape seed extract can also contribute to increased levels.

References:

Lee YT, Huang SQ, Lin CH, Pao LH, Chiu CH. Quantification of Gut Microbiota Dysbiosis-Related Organic Acids in Human Urine Using LC-MS/MS. Molecules. 2022 Aug 23;27(17):5363. doi: 10.3390/molecules27175363. PMID: 36080134; PMCID: PMC9457824.