Beneficial health effects of polyphenols metabolized by fermentation

Abstract

High daily intake of polyphenol-rich meal in some countries could be regarded as a healthy meal. However, the knowledge about the bioavailability and functionality of the exiting amounts of polyphenol into the large intestine needs to be elucidated, particularly the beneficial health effects and its fermentation characteristics during fermentation. Thus, this review focuses on the influence of polyphenols metabolized by fermentation and elucidates their health attributes. Besides, it also summarized the potential benefits of polyphenols and discussed the need for further research to fully understand the health attributes of polyphenols.

Graphical abstract

Introduction

Polyphenols are naturally occurring plant-based food component and categorically assigned to micronutrients because we need them in small quantities. Besides, the body cannot manufacture them and has to obtain them from food (Scalbert and Williamson, 2000). While polyphenols are mostly found in fruits, vegetables, seeds, and cereals, they are structurally varied in terms of formation (Tomás-Barberán and Espin, 2000; Vinson et al., 2001). Polyphenols are synthesized by plants as a means by which they use to defense against radiation and microbial infection (Haslam, 1998; Scalbert, 1991). Reports have indicated that more than 8000 polyphenols are identified so far and 4000 of which are flavonoids and categorically grouped into four categories, namely, flavonoids, phenolic acids, polyphenolic amides, and other polyphenols (Bravo, 1998; Harborne and Williams, 2000). Depending upon the chemical structure, polyphenols cannot be easily determined its absorbance level in the upper gastrointestinal tract (Cheynier 2005). However, gallic acid and isoflavones are the most well-absorbed phenolic compounds, followed by catechins, flavanones, and quercetin glucosides, but with different kinetics (Manach et al., 2005). The least well-absorbed polyphenols are anthocyanins, galloylated catechins, and proanthocyanidins (Manach et al., 2005). While as, the unabsorbed polyphenols which is accounted for more than 90% exited the small intestine into the large intestine and subsequently fermented by the large intestinal bacteria (Duynhoven et al., 2011; Kawabata et al., 2015). Consequently, this raises questions associated with its health attributes and a certain role by which polyphenols may play in the gut. Accordingly, studies have shown that the derived phytochemicals displayed positive attributes associated with health (Balentine et al., 1999; Kurulich et al., 1999). The findings were highly supported by investigators regarding the biological role of polyphenols in fighting against the degenerative diseases such as cancers, cardiovascular diseases, and neurodegenerative diseases (Duthie and Brown, 1994; Milner, 1994), which leads investigators to intensively investigate the biological role and health attributes of polyphenols. For instance, reports have indicated that polyphenols are potentially high in antioxidants, meaning, polyphenols can potentially reverse the oxidative stress caused by reactive oxygen species—a potential health risk associated with various diseases and disorders such as cardiovascular disease and cancer (Gu et al., 2014; Manach et al., 2004). After exiting the small intestine into the large intestine, the large intestinal bacteria use the polyphenols as a substrate and subsequently modulate the bacterial composition, and depending upon the amount and type, may exert specific response with ameliorative effects, such as the reduction of adipose tissue mRNA levels of tumor necrosis factor-α, interleukin-6 and inducible nitric oxide synthase, ameliorate the metabolic endotoxemia and improve the gut barrier function (Gu et al., 2014). Consequently, polyphenols promote or proliferate the population of healthy and beneficial bacteria and decreased the population of unhealthy bacteria. (Laparra and Sanz, 2010; Marín et al., 2015). Previously, it was reported that polyphenols modulate the microbial composition in the gut with their prebiotic potential and consequently enriched the favorable bacteria (Jiao et al., 2019; Lee et al., 2006; Peng et al., 2019a; 2019b). For example, Bifidobacterium population was increased by green tea polyphenols while reducing the population of harmful bacteria such as Clostridium difficile, Escherichia coli, and Salmonella (Dryden et al., 2006; Lee et al., 2006; Pacheco-Ordaz et al., 2018). Besides, the intestinal putrefactive products such as ammonia, indole, and skatole were reduced by the polyphenols, while the intestinal immunity-related substances (mucin and immunoglobulin A (IgA)) were reportedly been positively affected by the polyphenols (Goto et al., 1999; Taira et al., 2015). Thus, we have reviewed the influence of polyphenols metabolized by fermentation to assess and elucidate their health attributes.

Polyphenol and general health

The increasing interest in polyphenols-related research has led researchers or investigators in the recent past to learn and try to understand their potential health attributes and thus, studies associated with polyphenols have become an increasingly significant area of human nutrition research (Bahadoran et al., 2013; D'Archivio et al., 2007; Goutzourelas et al., 2015; Leopoldini et al., 2011; Martin and Appel, 2010; Sahpazidou et al., 2014). Researchers have also showed that the risk of type 2 diabetes was lowered and this was attributed to polyphenols, by dropping the blood-glucose spike, higher glucose tolerance, and increased insulin sensitivity by preventing the breakdown of starch to simple sugars (Azzini et al., 2017; Kim et al., 2016). Similarly, Grosso et al. (2017) reported that a polyphenol-rich food lowered the chances of getting type 2 diabetes by more than 50%. Additionally, studies have indicated that anthocyanin-rich food could be the most potent antidiabetic polyphenol amongst the many, which can be found in food sources such as berries, currants, grapes, and purple sweet potatoes (Khoo et al., 2017; Xiao and Högger, 2015). The alleviation of chronic diseases such as chronic inflammation and risk factors associated with heart diseases such as lowering of blood pressure and low-density lipoprotein were the attribution associated with the polyphenol’s antioxidant potential (Cheng et al., 2017; Hunter, 2012; Hussain et al., 2016; Potì et al., 2019; Tangney and Rasmussen, 2013). Besides, a lot of studies have linked high polyphenol-rich food consumption in reducing the risk of cancer, which is attributed to the antioxidant and anti-inflammatory effects (Dinu et al., 2017; Madigan and Karhu, 2018; Zhang and Tsao, 2016; Zhou et al., 2016). A meta-analysis study highlighted that a high intake of flavonols and flavones reduced the risk of breast cancer in women (Hui et al., 2013). Furthermore, studies have reported that polyphenols may potentially block the growth and development of cancerous cells which may link to lower the risk of breast and prostate cancers, but more studies are warranted to further elucidate before strong evidenced-based conclusions can be made (Niedzwiecki et al., 2016; Wang et al., 2015; Zhou et al., 2016). Table 1 highlighted some studies regarding polyphenol sources and their mechanism of action.

Table 1.

Polyphenols and mechanism of action

Representative polyphenols	Source	Study	Dosage/dose	Duration	Mechanism of action/health impacts	References
Pterostilbene	Blueberries	Rat injected with AOM	40 μg/g diet/day	45 weeks	Anti-inflammatory activity: decrease in mucosal levels of the proinflammatory cytokines (NF-α, IL-1β and IL-4) and expression of inflammatory markers	Paul et al. (2010)
Resveratrol	Bushy knotweed (Polygonum ramosissimum)	DSS mouse model of colitis	150–300 μg/g diet/day	3 weeks	Anti-inflammatory effect: decrease in IFN-γ and TNF-α secretions, tumor incidence, and multiplicity	Cui et al. (2010)
(-)-epicatechin, ( +)-catechin, and procyanidins	Cocoa	Rat model of AOM-induced colon carcinogenesis	12% cocoa in diet	8 weeks	Anti-inflammatory activity: decrease in the nuclear level of NF-κB and the expression of pro-inflammatory enzyme (cyclo-oxygenase-2)	Rodríguez-Ramiro et al. (2013)
Curcumin	Turmeric	Human colon cancer cells HCT116	5 μM curcumin	indicated time	Biochemical changes to mesenchymal-epithelial transition anti-proliferative activities	Buhrmann et al. (2014)
Hydroxytyrosol	Olive	Colon cancer cell lines	0.2–0.4% olive mill waste water	24–48 h incubation	Anti-inflammatory and anti-proliferative activities: decrease in apoptosis in CRC cells	Bassani et al. (2016)
Proanthocyanidins and anthocyanins	Cranberries	Mouse treated with AOM and DSS	1.5% cranberry diet	22 weeks	Anti-tumor and anti-inflammatory effects: decrease in IL-1β, IL-6, and TNF-α levels, and cell proliferation, apoptosis, angiogenesis and metastasis in the colon	Wu et al. (2018)
Anthocyanins	Cocoplum (Chrysobalanus icaco L.)	HT-29 colorectal adenocarcinoma cells	5–20 μg/mL anthocyanins	4 h incubation	Anti-inflammatory effect: decrease in TNF-α, IL-1β, IL-6 and NF-κB1 levels in decreased the cell proliferation	Venancio et al. (2017)
Phenolic acids and phenolic alcohols	Extra virgin olive oil	Caco-2 cells treated with oxysterols	25 μg/mL olive oil phenolic extract	Pretreatment for 30 min	Anti-inflammatory effect: decrease in H2O2 production, glutathione, IL-6 and IL-8 levels	Serra et al. (2018)

AOM azoxymethane, DSS dextran sulfate sodium

Colonic microbiota and health

The large intestine of humans particularly the distal area is the largest reservoir and diversity of microbiota of approximately 10¹¹–10¹² bacteria per gram of colonic content, and this accounts for approximately 60% of the fecal mass (Eckburget al., 2005; Guinane and Cotter, 2013). The bacterial colonization initially started at birth, and as it developed, it was influenced by a number of factors such as the delivery mode, infant diet, and medication effects (Gronlund et al., 1999). Mountzouris et al. (2002) reported that Bifidobacterium and Enterobacteria were the early colonizers of the large intestine, which may be differed in response to the incidence of infection and breast-to-formula-fed infants. Other studies have also indicated that the colonic microbiota of vaginally born infants was dominated by Atopobium, Lactobacillus, Prevotella, or Sneathia spp. with higher levels of Clostridium spp. while cesarean section infants have increased the levels of skin-associated bacteria such as Corynebacterium, Propionibacterium spp. and Staphylococcus spp. (Dominguez-Bello et al., 2010; Penders et al., 2006; Salminen et al., 2004). The early colonizers or pioneer bacteria are environmentally adapted at an early stage and consequently modulate the gene expression which will create an environment conducive for their increment while inhibiting the introduced bacteria (Xu and Gordon, 2003). On the other hand, chronic conditions such as cardiovascular diseases, colorectal cancer, diabetes, inflammatory bowel diseases, neurological diseases, and obesity are consequences of disturbances (dysbiosis) associated with the diversity and variability of the microbial composition which are linked with the host’s health (Del Rio et al., 2013; Saarela et al., 2002; Vaiserman et al., 2017). Further, other factors that normally influence the composition of microbiota are inactivity, and most importantly diet, hence, by modulating the microbial composition may subsequently trigger the susceptibility to diseases (Sonnenburg and Bäckhed, 2016). Thus, diet could be the most common modulator of colonic microbiota. Previously, studies have indicated that a diet high in dietary fiber is the model diet for healthy colonic microbiota because of its health attributes (Bosscher et al., 2009; Chong, 2014; Gibson et al., 1995). For instance, Bifidobacterium population was selectively increased by inulin while reducing the pathogenic ones (Pompei et al., 2008; van de Wiele et al., 2007). Likewise, the fermentation of complex carbohydrates increases the population of Prevotella spp. which is associated with higher levels of fecal short-chain fatty acid (SCFA) production (De Filippo et al., 2010). Additionally, a study was shown that soluble dietary fiber through microbial fermentation could be more efficiently improve the colonic barrier function by upregulating gene expressions of the gut barrier (Chen et al., 2019).

Polyphenols, colonic microbial interaction and health

As mentioned previously, more than 90% of polyphenols ended up in the large intestine intact in the form of glycosides and become a substrate for colonic microbiota (Kawabata et al., 2019; Mojzer et al., 2016). Besides the ‘prebiotic-like’ function and other health-associated effects of polyphenols, colonic modulation of bacteria and its associated health implications is being intensively investigated recently in an attempt to elucidate on other specific gut microbial species that may provide health benefits to the host. It was reported that the effect of polyphenol depends very much on the type and concentrations (Marsilio and Lanza, 1998; Rozès and Peres, 1998; Salih et al., 2000). For example, tea polyphenols inhibited the pathogenic bacterial growth such as Clostridium perfringens with limited effect on Bifidobacterium and Lactobacillus (Lee et al., 2006). As shown in Table 2, studies were recently reported that polyphenols can modulate the microbial composition with beneficial health attributes. For example, Marques et al. (2018) reported that blackberry anthocyanin-rich extract increases the diversity of the microbial composition. Tzounis et al. (2010) reported that a high-cocoa flavanol group modulates the microbial composition by increasing the population of Bifidobacterium and Lactobacillus. Besides, some studies have been conducted to elucidate the effect of polyphenols on the colonic microbiota and health relationship (Lee et al., 2018; Rodríguez-Daza et al., 2020). Proanthocyanidins in wild blueberry, for example, distinctively shaped the gut microbiota profile and influenced the glucose homeostasis and intestinal phenotypes in high-fat high-sucrose fed mice (Rodríguez-Daza et al., 2020). Similarly, Lee et al. (2018) reported that blueberry supplementation in high-fat-fed-rats influences gut microbiota, inflammation, and insulin resistance. In another study, modulation of microbial composition by chitin–glucan and pomegranate polyphenols improve the endothelial dysfunction (Neyrinck et al., 2019). Besides, a study by Fotschki et al. (2016) showed that anthocyanins in strawberry polyphenolic extract exert a positive response in the rat cecal environment. Similar study was also reported by Peng et al. (2019a; 2019b) which showed that a long-term intake of anthocyanins from Lycium ruthenicum Murray on the organism’s health and colonic microbiota, which could be a potential functional food ingredient. Notably, these studies and many other polyphenol-related studies have demonstrated that polyphenol-microbial interaction can potentially contribute to the host’s health. Table 3 highlighted the polyphenolic compounds and their associated gut health impacts.

Table 2.

Modulation of polyphenols on potentially beneficial and detrimental gut microbiota

Representative polyphenols	Source	Study	Dosage/dose	Duration	F/B	Potentially beneficial bacteria						Potentially detrimental bacteria			References
						Bifidobacteria	Lactobacillus	Akkermansia	Eubacterium	Bacteroides	Blautia	Clostridium	Enterobacter	Enterrococcus
Anthocyanins	Blackberry	In vivo	25 mg/kg body weight/day	17 weeks				↑				↓			Marques et al. (2018)
Catechin	Cocoa	Human	494 mg cocoa flavanols/day	4 week		↑	↑			↑		↓			Tzounis et al. (2010)
Caffeic acid	–	In vitro	10–100 μg/mL	48 h incubation	↑	↑				↑				↓	Parkar et al. (2013)
Chlorogenic acid	–	In vitro	10–100 μg/mL	48 h incubation	↑	↑				↑					Parkar et al. (2013)
Epicatechin	–	In vitro	150 mg/L	48 h incubation					↑		↑				Tzounis et al. (2008)
Chlorogenic and neochlorogenic acids, and rutin	Cherry	Human	8 oz. cherry concentrated juice/day	5 days		↑	↑	↑		↑		↓			Mayta-Apaza et al. (2018)
Catechin, epicatechin, and procyanidin	Red wine	Human	272 mL red wine/day	30 days	↓	↑	↑		↑			↓	↓		Moreno-Indias et al. (2016)
Catechins	Green tea	Human	1 L green tea/day	10 days		↑						↓			Jin et al. (2012)

F/B the ratio of Firmicutes/Bacteroidetes, ↑ Increase, ↓ Decrease

Table 3.

Polyphenol-microbial interactions and health impacts

Polyphenols	Source	Study	Dosage/dose	Duration	Microbial activities	Health impacts	References
Ellagitannins and ellagic acid	Fruits and plants	In vitro, in vivo and human	–	–	Modulation of microbiota	Antiproliferative/anticancer evidence, anti-inflammatory evidence	Larrosa et al. (2010)
Secoisolariciresinol diglucoside (SDG)	Flaxseed	In vivo	0.7–3.0 mg SDG/day	–	–	Antiproliferative/anticancer evidence, anti-inflammatory evidence	Adolphe et al. (2010)
Pinoresinol	–	In vitro	50 μmol/L	4 h incubation	–	Antiproliferative/anticancer evidence, anti-inflammatory evidence	During et al. (2012)
Genistein	Soy	In vitro and in vivo	–	–	–	Antiproliferative/anticancer evidence, anti-inflammatory evidence, cardioprotective	Ganai and Farooqi (2015)
Genistein	Soy	In vitro	30 μmol/L	24 h incubation	–	Antiproliferative/anticancer evidence, anti-inflammatory evidence, cardioprotective	Rahman et al. (2016)
Hesperidin and hesperetin	Citruses	In vitro and in vivo	–	–	–	Antiproliferative/anticancer evidence, anti-inflammatory evidence, cardioprotective, antiulcer, neuroprotective	Parhiz et al. (2015)

Polyphenol and SCFA production

SCFAs (primarily acetate, propionate, and n-butyrate) are produced in the gut by bacterial fermentation of non-digestible carbohydrates and exert several beneficial health effects (Patterson et al., 2014). For example, acetate, which accounts for the highest percentage of SCFAs produced in gut can potentially delay the proliferation of cancerous cells and prevent oxidative damage of the distal colonic cells (Abrahamse et al., 1999; Hague et al., 1995). Propionate, although it’s less studied than other SCFAs, also exert some health benefits to the host. For example, propionate is metabolized in the liver and subsequently used for gluconeogenesis (Wong et al., 2006), while n-butyrate is an important fuel for colonocytes (Robles Alonso and Guarner, 2013). While polyphenol increases the production of SCFA, the mechanism by which polyphenol increased the production of SCFA is not fully understood. However, it could be related with the anaerobic bacteria such as Bifidobacterium, Lactobacillus, and Ruminococcus (Li et al., 2019; Liu et al., 2018; 2019). Additionally, it could be the inhibitory effect of polyphenols towards α-amylase and α-glucosidase in saliva and small intestine, thus, providing colonic microbiota with residual carbohydrates for SCFA production (Henning et al., 2018). Besides, Zhu et al. (2013) reported that while polyphenols influence the microbial composition variations, the microbial conversion of polyphenol affects other pathways including pathways associated with SCFA productions. This was also reported by Larrosa et al. (2009) which states that grape polyphenol increased the population of bifidobacteria and lactobacilli, which can produce SCFA. Whereas, a high acetate level may be correlated with the metabolic activities of bifidobacteria and lactobacilli (Sanz et al., 2005a; 2005b). In another study, fecal microbial metabolism of polyphenols specifically increased the population of Bifidobacterium and simultaneously increase the metabolites, such as 3-hydroxyphenylacetic and 3-hydroxyphenylpropionic acids (Gronlund et al., 1999). Besides, it was also reported that the production of butyrate was correlated with bacterial metabolites (Dominika et al., 2011). Conversely, other authors reported that a high level of polyphenol in the diet may reduce the microbial composition and SCFA level (Kosmala et al., 2014; Negi and Jayaprakasha, 2001; Zduńczyk et al., 2006). Additionally, Etxeberria et al. (2015) and Wallace et al. (2015) reported that while other polyphenols sources may have an effect on SCFA production, boysenberry and trans-resveratrol did not cause any significant changes in SCFA production, particularly due to the different types of polyphenols, experimental model, and complexity of the microbiota.

Polyphenol and putrefactive products

Indigestible proteins enter the large intestine and become substrate for bacterial fermentation. Consequently, the proteolytic bacteria (mainly Bacteroides and Propionibacterium) ferment the indigestible proteins to putrefactive products (ammonia, p-cresol, 4-ethylphenol, indole, phenol, and skatole) (An et al., 2014). For example, p-cresol is an aromatic compound produced as a result of microbial fermentation of L-tyrosine (Macfarlane and Macfarlane, 1997; Windey et al., 2012). Likewise, indole is a microbial fermentation product of tryptophan-rich food such as soy protein (An et al., 2014). Production of putrefactive products in access are considered putative and could pose some serious health issues associated with colon cancer (Windey et al., 2012). Studies have shown that ammonia is detrimental to the host at a higher concentration and can affect the energy metabolism of colonic epithelial cells (Davila et al., 2013; Jing et al., 2020). Similarly, production of p-cresol at a higher concentration is associated with chronic disease development and liver failure (Brocca et al., 2013; Vanholder et al., 2014), while phenol and indole are putrefactive products that are directly associated with the epithelium by stimulating the strength of carcinogenic factors (Ma et al., 2017; Zhao et al., 2019). The production of putrefactive products is in most cases diet-related, and although they are detrimental and considered putative carcinogenic, they can be suppressed or prevented by the choice of diet. For example, diet rich in fruits and vegetables is inversely associated with health risks (Arts and Hollman, 2005; Del Rio et al., 2013; Hertog et al., 1993). Likewise, a polyphenol-rich diet could be a potential remedy for the high production of putrefactive products. In the recent past, studies have shown that polyphenols may reduce or suppress the production of putrefactive products (Jurgoński et al., 2014; Kilua et al., 2020; Yamakoshi et al. 2001). For example, Yamakoshi et al. (2001) reported that grape proanthocyanidin-rich extract significantly increased the fecal number of Bifidobacterium, while reducing the putrefactive bacteria. Similarly, Goto et al. (1999) reported that tea polyphenols positively affect the growth of Bifidobacterium spp. while reducing the putrefactive bacteria like Enterobacteriaceae spp. and Clostridium spp. and subsequently reduced the levels of ammonia and sulfides. In another study, Jurgoński et al. (2014) showed that supplementation with blackcurrant pomace reduced the putrefactive metabolites, similar to a report by Zduńczyk et al. (2006) on the ammonia–nitrogen level. Nagata et al. (2018) also reported that polyphenol-containing adzuki bean extract reduced the ammonia concentration in the rat cecum, while Bilić-Šobot et al. (2016) reported that hydrolysable tannins reduced the intestinal skatole production via lower synthesis of androstenone due to tannins. Therefore, based on studies regarding the positive attributes associated with polyphenol-rich diet, there is a great potential that it could be potentially developed into functional food ingredients for human consumption aiming to alleviate the detrimental effects associated with putrefactive products.

Polyphenol and intestinal immunity-related substances (Mucin and IgA)

Immunity refers to the body's ability to prevent the intrusion of pathogens (e.g. bacteria and viruses) or harmful substances that cause disease such as antigens. Intestinal immunity is associated with the responses by the epithelial to any possible invasion by upregulating the defense mechanisms or signals for immediate protection. This is in response to the constant challenge by the antigens, digestion products, and drugs to the intestinal mucosal lining because the microbial-epithelial crosstalk is such an important component central to the immune system (Belkaid and Harrison, 2017; Chen et al., 2018; Wells et al., 2011). In most cases, diet type is the main factor influencing and determining the immune system. For example, high dietary fiber diet and resistant starch enhances the mucin and IgA secretions via large bowel fermentation (Beukema et al., 2020; Desai et al., 2016; Tanabe et al., 2004). Besides, phenolic compounds are another groups of active compounds associated with the immunomodulatory activity which increases the secretions of mucin and IgA (Nagata et al., 2018; Szliszka and Krol, 2011; Taira et al., 2015).

The gel-like substance of mucus covering the epithelial layer can be regarded as the first line of defense against pathogenic bacterial growth (Johansson and Hansson, 2013; Johansson et al., 2008). Pelaseyed et al. (2014) reported that the key component of the mucus is mucin which is produced by the goblet cells in a single layer in the upper gastrointestinal tract/small intestine and a double layer in the colon. Studies have revealed that mucin secretion by the goblet cells was stimulated by the production of SCFA (Sakata and Setoyama, 1995; Shimotoyodome et al., 2000). Besides, Dohrman et al. (1998) reported that genes of mucin are up-regulated by the derived substances from bacteria such as lipopolysaccharides. Additionally, mucin was up-regulated by the prebiotic treatment (Carasi et al., 2015), which is associated with the type of diet (Beukema et al., 2020; Desai et al., 2016; Szliszka and Krol, 2011; Tanabe et al., 2004). There are many studies that have been conducted to verify that polyphenols are very influential in mucin secretions. For example, Nagata et al. (2018) and Taira et al. (2015) reported that adzuki bean extract and dietary polyphenols enhanced the cecal mucin concentration in rats. Similarly, in another study, ellagic acid and proanthocyanidin supplementation increased the secretion of mucin (Rosillo et al., 2011). Besides, dietary polyphenols may strengthen the viscoelastic modulus of the mucus layer via mucin cross-link, thus, mucus layer stabilization (Georgiades et al., 2014; Guri et al., 2015). Further, it was suggested that polyphenols are immune regulators (Lakhanpal and Rai, 2007), but the mechanism by which polyphenol influences the secretion of mucin is not fully understood. There are reports which could indicate the initiation steps towards its secretion and up-regulation. For example, polyphenols might stimulate the enzymatic activity via microbial modulation, and subsequently reduce the mucin-degrading enzymes and consequently increase the secretion of mucin (Fotschki et al., 2014; Selma et al., 2009).

On the other hand, IgA is a significant immunoglobulin in the body and responsible for mucosal homeostasis playing an important role against antigens (Breedvel and van Egmond, 2019; Mestecky and McGhee, 1987; Mkaddem et al., 2014). It was reported that an average adult produces approximately 3 g of antibodies per day, about two-thirds of this is IgA (Mestecky and McGhee, 1987). IgA is secreted by the plasma cells or mucosal-associated lymphoid tissues as a homogeneous population of cells and released as dimer joined by J-chain in external secretions as the first line of defense preventing accessibility of antigens to the submucosa and circulation (Corthésy, 2010; Mora and Andrian, 2008; Woof and Mestecky, 2005). According to Yazdani et al. (2017), IgA deficiency can lead to the production of anti-IgA antibodies which can weaken the mucosal barrier functions and subsequently expose the body to external pathogens. It was reported that recurrent sino-pulmonary infection is commonly associated with IgA deficiency (Vo Ngoc et al., 2017). Other related studies have shown that IgA deficiency is associated with gastrointestinal infections, allergy and autoimmunity (Aghamohammad et al., 2009; Ballow, 2002). As have been discussed earlier (Chen et al., 2019; De Filippo et al., 2010; Pompei et al., 2008; Van de Wiele et al., 2007), diet is the key influencer of colonic microbiota, and because of that, it influences the up-regulation of IgA responses and consequently selects for a microbiota composition in a reciprocal positive feedback loop for the host’s mucosal homeostasis (Kawamoto et al., 2014). Recently, the focus of investigation to elucidate the modulatory effects and fermentation characteristics was on polyphenols. Many of these studies have reported that polyphenols can up-regulate the level of IgA. For example, according to Taira et al. (2015), Aronia, Bilberry, and Haskap markedly elevated the amount of fecal IgA as an intestinal barrier function and ameliorated the disturbance in gut microbiota caused by a high-fat diet in rats. Likewise, Okazaki et al. (2010) reported that consumption of curcumin elevates fecal IgA, an index of intestinal immune function in rats fed a high-fat diet. Similarly, grape pomace supplementation increased the level of IgA in pigs (Williams et al., 2017). In another study, Peng et al. (2019a) reported that the cecal IgA content of mice was increased after anthocyanin intervention and a polyphenol-rich cocoa diet improved the barrier integrity and prevents intestinal inflammation in diabetic rats (Alvarez-Cilleros et al., 2020).

Therefore, this study highlights that polyphenols metabolized by fermentation do improve the fermentation characteristics and confer beneficial health attributes to the host, which suggests that the inclusion of polyphenols in the diet reduces the chances of pathogenic bacterial growth while increasing the growth of beneficial bacteria.

Declarations

Conflict of interest

No potential conflict of interest was reported by the authors.