Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

TLDR: While it is clear that the composition of the human gut microbiota can be modulated in vivo by supplementation with some (poly)phenol‐rich commodities, such modulation is definitely not an inevitable consequence of supplementation and it is not clear whether the modulation is sustained when supplementation ceases.

About: This article is published in Biochemical Pharmacology.The article was published on 2017-09-01 and is currently open access. It has received 227 citations till now.

Figures

Table 1: Comparison of plasma and colon catabolite concentrations in volunteers compared to concentrations shown to be effective in in vitro

Figure 8: Possible catabolic routes from hesperetin to hydroxyphenylhydracrylic acids.

Figure 6. Appearance of microbial metabolites in the plasma and urine from volunteers (n=22) after consumption of mixed berry fruits. Top panel: Plasma catechol-O-sulfate (ﾐ) and 1-methyl-pyrogallol-O-sulfate (ズ). Lower panel: Urinary catechol-O-sulfate. Redrawn from [87] and [86]. *, p < 0.05; **, p < 0.01 relative to time zero. Relative quantification is based on peak area corrected for the internal standard.

Figure 7. Measured concentration of 3胡-methoxy-4胡-hydroxy-phenylpropionic acid (DHFA) in plasma after consumption of one cup of coffee (ズ), or calculated after seven cups, one every 120 min (ﾐ). Data on single dose taken from [20] and is the DHFA plasma concentration after consumption of a cup of coffee (3.4 g of instant coffee in 200 ml water) containing 412 mg total chlorogenic acid. Effect of seven doses consumed every 120 min was calculated using simple addition of each time point from the single dose data, without taking into account any change in plasma clearance as a function of plasma concentration.

Figure 2: Diagrammatic illustration of the conversion of three classes of dominant dietary (poly)phenols to a series of common catabolites

Frequently asked questions

Q1. What have the authors contributed in "Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols" ?

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Q2. What have the authors stated for future works in "Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols" ?

Use of physiologically based kinetic ( PBK ) modeling to study interindividual human variation and species differences in plasma concentrations of quercetin and its metabolites, Biochem. Food Chem. 59 ( 6 ) ( 2011 ) 2241-2247. [ 176 ] K. M. Keane, P. G. Bell, J. K. Lodge, C. L. Constantinou, S. E. Jenkinson, R. Bass, G. Howatson, Phytochemical uptake following human consumption of Montmorency tart cherry ( L. Prunus cerasus ) and influence of phenolic acids on vascular smooth muscle cells in vitro, Eur. J. Nutr. 55 ( 4 ) ( 2016 ) 1695-1705. [ 177 ] M. Hidalgo, S. Martin-Santamaria, I. Recio, C. Sanchez-Moreno, B. de Pascual-Teresa, G. Rimbach, S. de Pascual-Teresa, Potential anti-inflammatory, anti-adhesive, anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of anthocyanins and their gut metabolites, Genes Nutr. 7 ( 2 ) ( 2012 ) 295-306. [ 178 ] M. Tognolini, C. Giorgio, M. Hassan, I, E. Barocelli, L. Calani, E. Reynaud, O. Dangles, G. Borges, A. Crozier, F. Brighenti, R. D. Del, Perturbation of the EphA2-EphrinA1 system in human prostate cancer cells by colonic ( poly ) phenol catabolites, J. Agric. The catabolites above might be absorbed and subject to mammalian metabolism ( glucuronidation, sulfation, methylation, hydrogenation, dehydrogenation, -oxidation ) and / or further microbiota catabolism ( hydrogenation, -oxidation, de-methoxylation, de-hydroxylation ) HO O OH OH HO O OH HO O OH OH HO O OH OH OH HO O OH HO O A selection of catabolites that are common to these substrates, found in plasma and / or urine as drawn or as conjugates ( glucuronidation, sulfation, methylation or glycination ) 0 100 200 300 400 500 0. 0 0. 5 p la s m a h e s p e re ti n ( M ) time ( min ) 0 100 200 300 400 500 0. 0 0. 5 p la s m a h e s p e re ti n ( M ) time ( min ) 0 100 200 300 400 500 600 0. 0 0. 5 1. 0 1. 5 2. 0 p la s m a h e s p e re ti n ( M ) time ( min ) 0 100 200 300 400 500 600 0. 0 0. 5 1. 0 1. 5 2. 0 p la s m a h e s p e re ti n ( M ) time ( min ) A B C D O O OH HO OHHO HO OH OHHO HO HO O OH OH OH OHO OH OH OH OH OHO OH OH OH OH OHO OH OH OH OH Specimen Proanthocyanidin Specimen Thearubigin A C B A A C C B A A C C B B 0h 0-2h 2-4h 4-8h 8-24h 0 10000 20000 30000 re la ti v e a m o u n t urine collection time * * * O OCH3 OH OOH HO HO OCH3 OH O HO HO OH O HO OCH3 OH O HO OCH3 OH O HO Ring scission Hydratase P450 acid 0. 02 µM, range 0. 006– 0. 08 µM [ 176 ] µM ely challenge d HUVECs producti on Gallic acid 1. 2 ± 1. 0 µM [ 82 ] 

Q3. How long does hesperetin take to be absorbed?

When hesperidin is consumed orally, hesperetin (conjugates of sulfate and glucuronide) appear in the plasma with a Tmax of 4-6 h. 

Q4. What is the role of phenols in the metabolisation of fatty acids?

It has also been demonstrated in vitro that the exposure to (poly)phenols modulates the ability of the microbiota to metabolise fructo-oligosaccharides and to generate short chain fatty acids [138, 139]. 

Q5. What are the likely substrates to dominate the microbial catabolites?

The catabolites most likely to dominate are the C6 phenols, C6–C1, C6– C2 and C6–C3 dihydro acids derived from chlorogenic acids/cinnamates, and most flavonoids including black tea thearubigins and theaflavins (see Figs. 2 and 5). 

Q6. What are the requirements for future investigations?

Future investigations must address the minimum effective dose of potentially prebiotic substrates, determine what percentage of the population are susceptible, whether susceptibility can be induced, and how long any associated benefits persist, especially if the supplementation is subsequently curtailed. 

Q7. What is the way to detect purely chemical transformations?

Some dietary (poly)phenols are unstable under the conditions employed for in vitro fermentations, and it is important to use an uninoculated control to detect purely chemical transformations. 

Q8. How did the consumption of dates affect the gut microbiota?

The consumption of seven dates per day by 22 volunteers for 21 days also did not alter the composition of the faecal microbiota, but stool ammonia was significantly lowered [112]. 

Q9. What is the approach to estimating the rate of clearance from plasma?

This approach assumes that the rate of clearance from plasma does not change with dose, and would only be true if clearance was saturated, and thus the estimate obtained is on the high side. 

Q10. What is the effect of coffee on the absorption of chlorogenic acids?

Having breakfast with coffee somewhat affected the timing of absorption, but not the overall amount absorbed [25], and non-dairy creamer, but not milk, has the same effect [26] and so the overall effect of food or beverages on the absorption and metabolism of chlorogenic acids appears to be minimal despite some reports to the contrary [27].