Phenolic compounds show reciprocal relationship

Phenolic compounds show reciprocal relationship with colonic microflora. Phenolic compounds are able to improve colonic health and modulate microbiota diversity with prebiotic and antimicrobial functions, while colonic bacterial enzymes catalyze deconjugation, dehydroxylation, and convert phenolic compounds in a complex mixture of simple phenolic acids which can also enter into the circulatory system (Ozdal et al., 2016, Velderrain-Rodriguez et al., 2014). After deconjugation, microbial metabolites are absorbed from the colon and transformated by the human cell enzymes into phase II conjugates resulting in their glucuronidated and sulfated derivatives. Through enterohepatic recirculation, the liver excretes conjugated compounds as components of bile into the intestine, and microbial enzymes regenerate the deconjugated compounds before being reabsorbed (Selma, Espín, & Tomás-Barberán, 2009). It is better to remind that phenolic compounds conversion depends several factors such as individual differences in microbiota, chemical structure of phenolic compounds, and co-consumed foods effects on interaction between phenolic compound and microbiota. Different types of phenolic compounds are degraded to different types of metabolites (simple phenolic compounds) derived from A and B rings after C ring degradation. For example, as a flavonol, quercetin is degraded to 2-(3,4-dihydroxyphenyl)acetic acid, 2-(3-hydroxyphenyl)acetic acid, and 3,4-dihydroxybenzoic imidazole sale from the B ring, whereas phloroglucinol, 3-(3,4-dihydroxyphenyl)propionic acid, and 3-(3-hydroxyphenyl) propionic acid are produced from the A ring (Selma et al., 2009). The flavanone degradation pathway is also similar to that observed in flavonols and other flavonoids, including procyanidins (Rechner et al., 2004). On the other hand, the colonic degradation products of flavan-3-ols (catechins) are not same as those from other flavonoids as flavan-3-ols does not include a carbonyl group or double bound in the 2–3 positions. Unlike these phenolic compounds, antocyanins are rarely metabolized by colonic microbiota as anthocyanin glycosides are more stable. The basic ring structure of isoflavones is also different from other flavonoids and the metabolites from colonic degradation consist p-ethylphenol and 4-hydroxyphenyl-2-propionic acid, O-demethylangolensin and equol. It was reported that equol showed higher antioxidant activity than isoflavones due to the greater flexibility for conformational changes, enabling it to penetrate more easily into the interior of the membrane to prevent oxidative damage in situ than some of the other isoflavonoids that are more rigid in structure (Selma et al., 2009, Yuan et al., 2007). It is obvious that gut microbiota metabolism regulate the health effects of dietary phenolics by altering their absorption, bioavailability, and biological activity. On the other side, it is also crucial to understand the inhibitory or stimulatory effect of phenolic compounds on beneficial or pathogenic bacteria, and their ratio in the gut. There are several studies investigating the phenolic compounds effects on gut microbiota (Duda-Chodak, 2012, Etxeberria et al., 2015, Kawabata et al., 2013). Duda-Chodak (2012) analyzed the different types of flavonoids effects on six pathogenic and beneficial bacterial species commonly found in gut microflora. They reported that quercetin, rutin, naringenin, and hesperetin showed inhibitory effects on all analyzed bacterial species (pathogenic and probiotic microorganisms). Parkar, Stevenson, and Skinner (2008) also showed that all tested phenolic compounds, except rutin, were effective on pathogenic strains in gut microbiota, whereas probiotic lactobacillus strains were relatively unaffected. In another study, it was concluded that catechin incubation with selected microbiota resulted in a significant increase in the growth of the Clostridium coccoides-Eubacterium rectale group, Bifidobacterium spp., and Escherichia coli, while a significant inhibitory effect on the growth of the Clostridium histolyticum group (Tzounis et al., 2008). It is obvious that the decrease in growth of pathogenic strains is related to the antimicrobial effects of phenolic compounds. The increase of the probiotic strains could be related to its capacity to metabolize these flavonoid compounds for stimulating their growth. Generally, flavonols, isoflavones and glycosides were found to have a low antibacterial activity and phenolic acids were intermediate. The tested flavanone and flavanol had high antibacterial activity (Parkar et al., 2008). However, there was no noticeable relationship between structure and activity as well as mechanistic explanation about the inhibitory or prebiotic activity of phenolic compounds. More studies considering the inter-individual differences in gut microbiota combination with in vitro and in vivo methods should also be performed to elucidate the interaction between gut microbiota and phenolic compounds mechanistically. Even so, latest studies emphasized that the regular consumption of phenolic compound–rich foods in a diet may beneficially balance the gut microbiota and exert beneficial health effects related to inflammation and obesity. The concept of the ‘three P's for gut health,’ that includes probiotics, prebiotics, and phenolic compounds, has been recently created, and it promotes phenolic compounds to the same biological level of prebiotics (Espín et al., 2017, Marchesi et al., 2015). Firstly, the high number of studies has highlighted that phenolic compounds have biological effects against colon cancer, cell proliferation, intestinal inflammation. However, recent insights also indicated that high intake of phenolic compounds from different sources regulated some cardiovascular diseases risk factors and brain function through the modulation of microbial populations and activities (Martín-Peláez et al., 2017). One of the issues that emerges from these findings is that antioxidants bound to dietary fiber reaches the colon without being digested in the small intestine and they play a major role in the reduction of local oxidative stress and in modifying the microbiota composition as mentioned below. They have also come into prominence with their continuous presence in a relatively low concentration that is providing a greater potential benefit for the body's defense than the peak of plasma antioxidant concentration observed immediately after the ingestion of a food rich in free phenolic compounds (Vitaglione, Napolitano, & Fogliano, 2008).