This paper summarises the occurrence in foods and beverages of the cinnamic acids, their associated conjugates and transformation products. Quantitative data are lacking for some commodities known to contain them, but it is clear that for many people coffee will be the major source. The daily dietary intake of total cinnamates may vary substantially from almost zero to perhaps close to 1 g. The data relating to their absorption and metabolism are presented along with a consideration of their possible in vivo effects. Data for true bioavailability are incomplete: in particular it is not clear whether availability differs markedly with the form of the conjugate, and whether as a consequence some dietary sources may be superior to others.

Chlorogenic acids and other cinnamates - nature, occurrence, dietary burden, absorption and metabolism

Chlorogenic acid, the ester of caffeic acid with quinic acid, is one of the most abundant polyphenols in the human diet with coffee, fruits and vegetables as its major sources. Its antioxidant and anticarcinogenic properties have been well established in animal studies. However, little is known about its gut absorption and metabolism. In the present work, four groups of rats (n = 8) were fed a diet supplemented with chlorogenic, caffeic or quinic acids (250 micromol/d) or an unsupplemented diet for 8 d. Parent compounds and their metabolites were estimated in urine (24-h collection) and plasma by HPLC-electrospray ionization-tandem mass spectrometry. Significant differences in their levels were observed among the groups. The recovery of chlorogenic acid in urine was low (0.8%, mol/mol), and the total urinary excretion of caffeic acid liberated by hydrolysis of chlorogenic acid and its tissular methylated metabolites (ferulic and isoferulic acids) did not account for >0.5% (mol/mol) of the dose ingested. On the other hand, the metabolites of microbial origin, namely, m-coumaric acid and derivatives of phenylpropionic, benzoic and hippuric acids, represented the major compounds in both urine and plasma. Hippuric acid largely originated from the transformation of the quinic acid moiety, and all other metabolites from the caffeic acid moiety. These microbial metabolites accounted for 57.4% (mol/mol) of the chlorogenic acid intake. Such a high abundance of microbial metabolites shows that the bioavailability of chlorogenic acid depends largely on its metabolism by the gut microflora. Their potential importance in explaining the biological effects of dietary polyphenols is emphasized.

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Chlorogenic Acid Bioavailability Largely Depends on Its Metabolism by the Gut Microflora in Rats

Strategies such as genomics, proteomics and metabonomics are being applied with increasing frequency in the pharmaceutical industry. For each of these approaches, toxicological response can be measured by terms of deviation from control or baseline status. However, in order to accurately define drug-induced response, it is necessary to characterize the normal degree of physiological variation in the absence of stimuli. Here, 1H NMR spectroscopic-based analyses of the metabolic composition of urine in experimental animals under various normal physiological conditions are reviewed. In particular, the effects of inter-animal and diurnal variation, gender, age, diet, species, strain, hormonal status and stress on the biochemical composition of urine are explored. Pattern recognition methods facilitate the comparison of urine NMR spectra over a given time-course, enabling the establishment of changes in profile and highlighting the dynamic metabolic status of an organism. Thus metabonomic approaches based on information-rich spectroscopic data sets can be used to evaluate normal physiological variation and for investigation of drug safety issues.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/nbm.935

NMR‐based metabonomic approaches for evaluating physiological influences on biofluid composition

The transgenomic metabolic effects of exposure to either Lactobacillus paracasei or Lactobacillus rhamnosus probiotics have been measured and mapped in humanized extended genome mice (germ-free mice colonized with human baby flora). Statistical analysis of the compartmental fluctuations in diverse metabolic compartments, including biofluids, tissue and cecal short-chain fatty acids (SCFAs) in relation to microbial population modulation generated a novel top-down systems biology view of the host response to probiotic intervention. Probiotic exposure exerted microbiome modification and resulted in altered hepatic lipid metabolism coupled with lowered plasma lipoprotein levels and apparent stimulated glycolysis. Probiotic treatments also altered a diverse range of pathways outcomes, including amino-acid metabolism, methylamines and SCFAs. The novel application of hierarchical-principal component analysis allowed visualization of multicompartmental transgenomic metabolic interactions that could also be resolved at the compartment and pathway level. These integrated system investigations demonstrate the potential of metabolic profiling as a top-down systems biology driver for investigating the mechanistic basis of probiotic action and the therapeutic surveillance of the gut microbial activity related to dietary supplementation of probiotics.

https://www.embopress.org/doi/pdf/10.1038/msb4100190

Probiotic modulation of symbiotic gut microbial–host metabolic interactions in a humanized microbiome mouse model

The absorption of dietary phenols, polyphenols and tannins (PPT) is an essential step for biological activity and effects on health. Although a proportion of these dietary bioactive compounds are absorbed intact, depending on their chemical structure and the nature of any attached moiety (e.g. sugar, organic acid), substantial amounts of lower molecular weight catabolites are absorbed after biotransformation by the colon microflora. The main products in the colon are (a) benzoic acids (C6-C1), especially benzoic acid and protocatechuic acid; (b) phenylacetic acids (C6-C2), especially phenylacetic acid per se; (c) phenylpropionic acids (C6-C3), where the latter are almost entirely in the dihydro form, notably dihydrocaffeic acid, dihydroferulic acid, phenylpropionic acid and 3-(3'-hydroxyphenyl)-propionic acid. As a result of this biotransformation, some of these compounds can each reach mm concentrations in faecal water. Many of these catabolites are efficiently absorbed in the colon, appear in the blood and are ultimately excreted in the urine. In the case of certain polyphenols, such as anthocyanins, these catabolites are major products in vivo; protocatechuic acid is reported to represent a substantial amount of the ingested dose of cyanidin-3-O-glucoside. The major catabolites of berries, and especially blackcurrants, are predicted based on compositional data for polyphenols from berries and other sources. Since microbial catabolites may be present at many sites of the body in higher concentration than the parent compound, it is proposed that at least a part of the biological activities ascribed to berry polyphenols and other PPT are due to their colonic catabolites.

/pdf/colonic-metabolites-of-berry-polyphenols-the-missing-link-to-ffjh4fg43b.pdf

Colonic metabolites of berry polyphenols: the missing link to biological activity?

Purified tribulin, an endogenous monoamine oxidase (MAO) inhibitor, has been identified by direct probe insertion mass spectrometry as the indole-2,3-dione, isatin. A gas chromatographic-mass spectrometric assay for isatin has been developed and used to measure its relatively high concentrations in unpurified human urine, and in rat heart and brain. Isatin is a known compound with a broad range of biological activity; this is the first report of its presence in the animal body. Isatin is a potent inhibitor of MAO, particularly of MAO B (IC50, 3 microM), and also binds to central benzodiazepine receptors (IC50 against clonazepam, 123 microM).

Isatin: Identity with the Purified Endogenous Monoamine Oxidase Inhibitor Tribulin

Gut flora and the origin of some urinary aromatic phenolic compounds

Inhibitory potency of some isatin analogues on human monoamine oxidase A and B.

Isatin (indole-2,3-dione) in urine and tissues. Detection and determination by gas chromatography-mass spectrometry.

This study was carried out to explore the value of the tyramine conjugation test, an established trait marker for 'endogenous unipolar depression', in patients with chronic idiopathic temporomandibular joint and orofacial pain. Our results show that the pain patients excrete significantly lower amounts of tyramine sulphate than controls (P < 0.0004). Psychiatric assessment by the structured clinical interview for the diagnosis of mental disorders according to DSM-III-R revealed that 48% of the patients had a history of depression and 10% were currently depressed. However, the never-depressed group of patients had the lowest tyramine sulphate excretion values. These findings suggest that a common biological abnormality underlies the pathogenesis of both chronic idiopathic facial pain and depression.

B.L. Goodwin

Papers

Isatin: Identity with the Purified Endogenous Monoamine Oxidase Inhibitor Tribulin

Gut flora and the origin of some urinary aromatic phenolic compounds

Inhibitory potency of some isatin analogues on human monoamine oxidase A and B.

Isatin (indole-2,3-dione) in urine and tissues. Detection and determination by gas chromatography-mass spectrometry.

Tyramine conjugation deficit in patients with chronic idiopathic temporomandibular joint and orofacial pain.