Composition, distribution, extraction, and identification

Phenolic compounds from mango residues can be classified into phenolic acids, flavonoids, gallates and gallotannins, ellagitannins, and others (benzophenones, xanthones, and lignans) [Ballesteros-Vivas et al., 2019a; De Ancos et al., 2018; Torres-León et al., 2021] as listed in Table 1. These compounds can be found in both free and bound forms [Alañón et al., 2021a; Gómez-Caravaca et al., 2016; Pacheco-Ordaz et al., 2018a]. Generally, the bound compounds are low molecular weight phenolics that may be interacting with macromolecules or cell wall components such as dietary fiber; these can be phenolic acids such as gallic, p-hydroxybenzoic, vanillic, protocatechuic, p-coumaric, ferulic, ellagic, as well as trans and cis-p-coumaric acids [Abbasi et al., 2017; Anaya-Loyola et al., 2020; Hernández-Maldonado et al., 2019]. Gómez-Caravaca et al. [2016] reported ellagic acid as the main bound phenolic in the pulp and peel fruit, as well as the husk and the seed kernel. The authors have remarked that this compound is responsible for 88.7% of the bound phenolics in the peel of mango fruit. Nonetheless, the variation of phenolic composition and biological activities in mango depends on the plant variety or cultivar, its geographic origin, growing conditions, age, fruit harvest time, degree of maturity, processing, and storage conditions [Abdel-Aty et al., 2018; Alañón et al., 2021a; Marcillo-Parra et al., 2021; Sáyago-Ayerdi et al., 2019]. For example, fisetin and mangiferin have been found in higher contents in the mango peel of the cultivar Xiao Tainong compared to other varieties [Abbasi et al., 2017]. It has also been reported that the Keitt mango peel had a significantly higher total phenolic content than the Kent and Osteen varieties; mainly due to the presence of galloyl glucose, 5-galloylquinic acid, digalloylquinic acid, hexagalloyl glucose, and galloyl glucoside [Alañón et al., 2021a]. Moreover, it was reported that green mango peels had about 45% higher content of phenolics than ripe mango. This trend has been associated with the mango ripening process because physiological, biochemical, and molecular changes develop, inducing the degradation, synthesis, or accumulation of phenolic compounds [Alañón et al., 2021b; Hu et al., 2018].

Nowadays, phenolics from natural sources are attracting increased attention for their bioactivities. For that reason, many studies have focused on improving extraction techniques and characterization of phenolic profiles. Due to the vast diversity of phenolic compounds, no common global strategy has been developed to carry out their extraction and identification. They differ in physical and chemical properties, and above all in solubility, which is why the efficiency of their extraction process depends mainly on the solvents and techniques used. Moreover, the source from which they are obtained determines the extraction process since phenolic compounds can interact with other components of the matrix and, as mentioned above, can be present in the tissues in free or bound form [Abbasi et al., 2017; Alañón et al., 2021a; Pacheco-Ordaz et al., 2018a]. Hence, the need arises to develop the optimum and appropriate methods for their proper extraction and purification. Essential factors for optimal extraction, such as pH, time, and temperature, have been considered [Ballesteros-Vivas et al., 2019a; Castañeda-Valbuena et al., 2021; Martínez-Ramos et al., 2020]. However, the most important aspect is the solvent type used (Table 1). The solvents used so far in the case of mango by-products included ethanol (50, 80, 96, and 100%, v/v) [Azhar et al., 2019; Buelvas-Puello et al., 2021; Gómez-Maldonado et al., 2020], methanol (50 and 100%, v/v) [Castro-Vargas et al., 2019; Hoyos-Arbeláez et al., 2018], ethyl acetate [Ballesteros-Vivas et al., 2019a; Torres-León et al., 2021], and hexane [Martínez-Ramos et al., 2020; Torres-León et al., 2021].

Numerous phenolic compounds have been identified and characterized through different approaches. For instance, Ballesteros-Vivas et al. [2019a] identified xanthones, phenolic acids, flavonoids, and gallotannins in mango seed kernels. Different contents of mangiferin were determined, depending on the solvent type and extraction method used, i.e.: 13.27 mg/g when absolute ethanol and pressurized liquid were applied; 13.60 and 12.34 mg/g when kernels were macerated in 50% (v/v) and absolute ethanol, respectively. In turn, Martínez-Ramos et al. [2020] reported that the ethanol-to-acetone ratio of the extraction mixture affected the extraction efficiency of phenolic compounds from mango peel residues during conventional and ultrasound-assisted processes. Furthermore, they showed that the composition of solvent mixtures and ultrasonic power influenced the solvent-solute interaction. On the other hand, Castañeda-Valbuena et al. [2021] established that variations in the solvent-solid ratio and solvent concentration used to obtain mango peel and seed extracts influenced their antioxidant capacity evaluated by different methods (DPPH, ABTS, and FRAP assays). The conventional and new alternative techniques deployed so far for the extraction of phenolic compounds from residues mango include: maceration [Ballesteros-Vivas et al., 2019a; Borrás-Enríquez et al., 2021; Safdar et al., 2017], agitation [El-Kady et al., 2017; Martínez-Ramos et al., 2020], Soxhlet and solvent extraction [Buelvas-Puello et al., 2021; Castro-Vargas et al., 2019; Torres-León et al., 2021], solid-liquid extraction, ultrasound-assisted extraction [Borrás-Enríquez et al., 2021; Castañeda-Valbuena et al., 2021; Lopez-Martinez et al., 2022], microwave-assisted extraction [Martínez-Ramos et al., 2020; Sánchez-Camargo et al., 2021; Torres-León et al., 2017], extraction assisted by fermentation [Torres-León et al., 2021], high hydrostatic pressure [Cádiz-Gurrea et al., 2020; Sánchez-Camargo et al., 2021], extraction with supercritical fluids [Ballesteros-Vivas et al., 2019b; Buelvas-Puello et al., 2021; Sánchez-Camargo et al., 2019], and extraction with pressurized fluids [Santana et al., 2019].

Recent trends in the valorization of agro-industrial wastes are focused on minimizing the environmental impact through the circular economy model. In this context, green techniques are essential to reduce the adverse effects on human health and the environment. Thereby, using green solvents in phenolic extraction provides more environmentally friendly and sustainable processes [Cádiz-Gurrea et al., 2020; Oliver-Simancas et al., 2021]. Ballesteros-Vivas et al. [2019a] proposed the integrated approach of green extraction, based upon sequential pressurized liquid extraction (PLE) to obtain fractions rich in bioactive compounds. The extraction of bioactive components with high antioxidant and antiproliferative capacity from residues of the mango seeds was optimized; the most efficient proved to be the mixture of ethanol/ethyl acetate (50:50, v/v) at 25°C and 1.01 bar, based on Hansen’s solubility parameters (HSP). PLE is an alternative technology to reduce environmental pollution generated by standard extraction methods. This technique allows for higher extraction yields of bioactive compounds with lower solvent consumption and shorter extraction time [Cádiz-Gurrea et al., 2020].

Regarding the identification and quantification (Table 1) of the phenolic compounds of mango residues, various methods based on liquid chromatography (HPLC, UPLC) with detection by UV-Vis detector or DAD were used [Buelvas-Puello et al., 2021; Lopez-Martinez et al., 2022; Sánchez-Camargo et al., 2019]. The techniques combining liquid chromatography with mass spectrometry were also often applied: RPHPLC-ESI-MS [Torres-León et al., 2017, 2021], HPLC-DAD-MS [Hernández-Maldonado et al., 2019], HPLC-DAD-ESI-QTOF-MS [Alañón et al., 2021a, b; Gómez-Caravaca et al., 2016; López-Cobo et al., 2017], [UPLC-DAD-ESI-MS [Navarro et al., 2019], UPLC-ESI-QTOF-MS [Anaya-Loyola et al., 2020; Hu et al., 2018], and LC-QTOF-MS/MS [Ballesteros-Vivas et al., 2019a; Sánchez-Camargo et al., 2021]. Other chromatographic techniques successfully used to identify mango bioactive compounds were HPTLC [Jyotshna et al., 2015] and GC-QTOF-MS [López-Cobo et al., 2017].

Mango agro-industrial wastes contain xanthonoids in the C-glucoside form, such as mangiferin. This polyphenol and some of its derivatives, such as methoxymangiferin and isomangiferin, have been detected in the peel and kernel residues [Alañón et al., 2021a, b; Anaya-Loyola et al., 2020; Marcillo-Parra et al., 2021]. Mangiferin has been reported to possess numerous beneficial properties, such as antioxidant, anti-inflammatory, antiviral, antiparasitic, and antimicrobial activities [Anaya-Loyola et al., 2020; Hernández-Maldonado et al., 2019; Vazquez-Olivo et al., 2019]. Mango residues also contain gallic acid, its numerous derivatives and gallotannins. Gallotannins are hydrolysable tannins with a structure of polymeric chains of gallic acid esterified with glucose. Gallotannins and their derivatives represent 20–28% of the total phenolic content in the mango peel. Overall, they are recognized as mango nutraceutical components for their pharmacological effects and functional properties [Alañón et al., 2021a]. Interestingly, the gallotannins identified in the mango seed kernels were considered as an indicator of the degree of maturation among multiple mango varieties [Alañón et al., 2021b; Torres-León et al., 2021]. Yet, another study with residues of the Ataulfo variety identified 47 phenolic compounds by UPLC-ESI-QTOF MS [Anaya-Loyola et al., 2020]. Of these, 35 were detected in the extractable fraction and 12 in the fraction after acid hydrolysis. The extractable fraction contained gallotannins, such as heptagalloyl hexose, hexagalloyl hexose, pentagalloyl hexose, tetragalloyl hexose, and some gallic acid derivatives (gallic acid hexoside, gallic acid dihexoside, and galloylquinic acid). In contrast, the fraction obtained after hydrolysis contained 59% of ellagic acid and 22.4% of gallic acid, and other phenolics, like rhamnetin, syringic acid, and vanillic acid.

Roles of phenolic compounds from mango wastes in human health promotion and disease prevention

Phenolic compounds exhibit a wide range of bioactivities exerting beneficial effects on health, such as anti-allergenic, hypolipidemic, antidiabetic, antiatherogenic, anti-inflammatory, anti-microbial, antiviral, immunomodulatory, antiproliferative, anticarcinogenic, antioxidant, anti-thrombotic, cardioprotective, and vasodilatory effects, as shown in Table 2. In this context, some mechanisms of their action in preventing or reducing the risk of various chronic diseases have been discovered [Abbasi et al., 2017; Alañón et al., 2021a, b; Kim et al., 2018; Lin et al., 2020].

Bioaccessibility and bioavailability of phenolic compounds

In the case of phenolic compounds, bioaccessibility refers to the phenolic fraction released from the food matrix during gastrointestinal phase digestion and made available for intestinal absorption. In contrast, bioavailability relates to the phenolic fraction or its derivatives that reach the bloodstream by intestinal absorption and become available for body functions at the site of action [Blancas-Benitez et al., 2015; Hernández-Maldonado et al., 2019; Jamar et al., 2017; Peanparkdee & Iwamoto, 2022]. Therefore, the biological contribution of phenolic compounds in the human body depends on numerous factors, such as the host condition, its gut microbiota, and the chemical and structural nature of the molecules. Firstly, the bioaccessibility and bioavailability of different phenolics vary depending on the individual’s physical condition, including digestive/absorptive/metabolic/response capability and effective dose. After ingestion, the release of phenolic compounds begins with the cellular compartmentalization and enzymatic hydrolysis of salivary α-amylases. Then, in the gastric phase, they interact with endogenous enzymes influencing the digestibility of the components of the food matrix, such as starch (α-amylase), lipids (pancreatic lipase), and proteins (pepsin and trypsin) [Peanparkdee & Iwamoto, 2022; Wu et al., 2017]. Then, multiple enzymes endowed with diverse metabolic capacities in the human gut microbiome contribute to the absorption of phenolics by their transformation or degradation [Bento-Silva et al., 2020; Blancas-Benitez et al., 2015; Hernández-Maldonado et al., 2019; Jamar et al., 2017; Pacheco-Ordaz et al., 2018a; Vazquez-Olivo et al., 2019; Velderrain-Rodríguez et al., 2018]. However, it has been reported that up to 65% of anthocyanins present in the diet are not absorbed in the gastrointestinal tract [Tian et al., 2019]. The phenolic compounds’ absorption also depends on their molecular structure, composition (free form or interacting with another component), and the degree of polymerization, which influences their solubility, permeability, and molecular stability.

Many authors have focused on knowing the bioaccessibility and bioavailability of mango phenolic. For instance, Blancas-Benitez et al. [2015] determined the phenolic bioaccessibility in the mango peel using an in vitro digestion system. As a result, a relative bioaccessibility of 43.53% was found. The vanillic acid and hydroxycinnamic acids were accessible for absorption in the small intestine and available to exert beneficial health effects. Hernández-Maldonado et al. [2019] found that 54% of the phenolic compounds in a mango-based bar were absorbed during the gastrointestinal phase, while 46% were hydrolyzed in the colon. Both research results regarding low bioaccessibility could be associated with the instability of the compounds that tend to degrade during intestinal digestion, such as phenolic acids, catechin, quercetin, resveratrol, and rutin [Peanparkdee & Iwamoto, 2022; Tian et al., 2019]. In this same sense, resistant compounds that reach the small intestine have also been observed. For example, Velderrain-Rodríguez et al. [2018] determined the absorption probability of phenolics from the Ataulfo mango peel in enterocytesin. They found a wide range of compounds with different relative absorption rates, such as p-coumaric and 2-hydroxycinnamic acid (89%), ferulic acid (86%), syringic acid (83%), protocatechuic acid (82%), gallic acid (75%), catechin (71%), quercetin (64%), ellagic acid (60%), mangiferin (40%), and rutin (16%). Herein, gallic acid and derivatives showed an absorption percentage higher than 57%, indicating better cell permeability. This result could potentially be associated with the antiproliferative effect reported for gallic acid. In addition, Pacheco-Ordaz et al. [2018a] evaluated the acid and alkaline hydrolysis of Ataulfo mango peel extracts using Caco-2 cell monolayers as a model for intestinal epithelial permeability. They reported gallic acid from an alkaline fraction presented an apparent permeability coefficient of 2.61×10^-6 cm/s compared to the standard of 2.48×10^-6 cm/s. Overall, the results suggest that most phenolic compounds (except for rutin) could be considered bioaccessible at the intestinal level; and some compounds could be even absorbed.

The conjugation of hydroxybenzoic acids limits bioaccessibility and bioavailability of some oligomers, such as gallotannins and ellagotannins formed from gallic acid and ellagic acid, respectively [Bento-Silva et al., 2020; Velderrain-Rodríguez et al., 2018]. Under gastrointestinal phase conditions, these compounds are hydrolyzed to simple molecules, like gallic acid [Anaya-Loyola et al., 2020]. However, branched-chain tannins that are not absorbable in their native form can be hydrolyzed and decarboxylated by microbial enzymes. The resulting metabolites, such as gallic acid and pyrogallol, can be absorbed in the colon [Kim et al., 2018]. In this same sense, mangiferin also is a compound with low absorption and little bioavailability compared to other phenolic components. Thereby, it should form complexes with other molecules to improve its solubility, food release, bioavailability, and other properties [Lin et al., 2020; Velderrain-Rodríguez et al., 2018]. However, compounds such as mangiferin gallate can undergo hydrolysis during gastric digestion, which leads to the mangiferin release [Hernández-Maldonado et al., 2019]. On the contrary, hydroxycinnamic acids and kaempferol require intestinal enzymes for absorption. In this regard, chlorogenic acid is a compound with low intestinal absorption. However, its bioavailability depends also on the metabolism of the gut microbiota. It has even been reported that it promotes the modulation of the colonic microbiota through stimulating the growth of Bifidobacterium spp., Clostridium coccoides, and Eubacterium rectale [Coman & Vodnar, 2020]. Therefore, these scientific works suggest that the mango wastes’ phenolic compounds can be modified not only to enhance their intestinal absorption but also to achieve their profiles enhancing the gut microbiota.

Understanding the bioaccessibility and bioavailability of phenolic compounds is crucial to establishing a functional characterization. For that reason, many researchers have focused on deciphering these mechanisms through different approaches. For instance, a significant effect on the release of phenolic compounds during an in vitro gastrointestinal simulation was observed in a study using a mango product with high total soluble phenolic contents. Herein, gastric digestion showed a release rate of 9% higher than the intestinal phase [Hernández-Maldonado et al., 2019]. These results could be associated with covalent interactions of the phenolic compounds with the polysaccharides of the cell wall [Hernández-Maldonado et al., 2019; Wu et al., 2017]. In addition, glycosidic bonds from polyphenols can be broken down by acid hydrolysis, causing the release of aglycones [Pacheco-Ordaz et al., 2018a].

In the intestinal section, the release of phenolic compounds is affected by pH changes and enzymes activity (mainly pancreatin and α-amylase). Both factors weaken molecular interactions in the food matrix, promoting bond hydrolysis. Particularly, intestinal esterases hydrolyze ester bonds between carbohydrates linked to phenolic compounds and other cell wall components in plants, increasing the bioavailability of phenolic compounds. They may be then absorbed by the gastrointestinal barrier and get into blood circulation. Generally, phenolic compounds are not fully absorbed by their structural complexity, and around 90% of these compounds reach the colon where they are fermented by intestinal microorganisms. Here, about 2,671 microbial species exist, constituting the human gut microbiota [Lagier et al., 2018; Ye et al., 2022]. These microorganisms are genetically endowed with enzymes such as esterases, lipases, carbohydrates, and proteases. Among them, α-l-rhamnosidases, β-d-glucosidase, and β-d-glucuronidases allow the release, absorption, and production of metabolites, such as bioactive phenolic acids, including gallic acid, protocatechuic acid, syringic acid, and vanillic acid [Bento-Silva et al., 2020; Coman & Vodnar, 2020; Hernández-Maldonado et al., 2019; Jamar et al., 2017; Pacheco-Ordaz et al., 2018a; Tian et al., 2019].

Interestingly, a recent study evaluated the phenolic compounds’ bioaccessibility in a mango pulp and peel-based bar during gastrointestinal phase and after fermentation [Hernández-Maldonado et al., 2019]. The results of this research identified not only phenolic acids (gallic, ferulic, coumaric, and caffeic acid) but also flavonoids and xanthones (quercetin, gallocatechin, mangiferin, and mangiferin gallate), reporting their 53.78% bioaccessibility. Likewise, products after fermentation were hydroxyphenolic acids and acetic acids as the primary shortchain fatty acids. In addition, norathyriol classified as xanthone (aglycone) was identified after 12 h of fermentation. Mango peel’s total soluble phenolic bioaccessibility has been reported at 44%. Soluble and released by hydrolysis phenolics represent only 11.46% of the insoluble fiber content. Hence then, nonbioaccessible and released soluble phenolics can reach the colon and potentially be used as substrates by the colonic microbiota [Hernández-Maldonado et al., 2019; Sáyago-Ayerdi et al., 2019]. Thereby, the insoluble fiber composition can influence microbiota composition changes during the fermentation process.

The gut microbiota plays a critical function in the biotransformation of phytochemicals, modulating the phenolic compounds’ bioavailability and promoting gut health [Bento-Silva et al., 2020; Hernández-Maldonado et al., 2019; Kim et al., 2018]. Therefore, the consumption of probiotics, prebiotics (dietary fiber), and phenolic compounds is recommended for better gut health, considering that phenolic molecules have the same biological effect as prebiotics [Hernández-Maldonado et al., 2019; Ye et al., 2022].

Gut health and modulation of the gut microbiota

The intake of fruits and vegetables is closely related with gut health because their bioactive compounds exert beneficial effects, such as phenolic compounds that remain bioaccessible after the gastrointestinal phase in the non-digestible fraction [Hernández-Maldonado et al., 2019; Kim et al., 2020; Pacheco-Ordaz et al., 2018a]. Hydroxycinnamic acids, gallotannins, and other compounds interacting with the fiber have been found therein [Hernández-Maldonado et al., 2019; Sáyago-Ayerdi et al., 2019; Velderrain-Rodríguez et al., 2018]. Also flavonoids and xanthones associated with the insoluble fiber fraction have been identified in mango, including quercetin, kaempferol, and mangiferin. Notably, as shown by assays with the fecal microbiota, this flavonoid-xanthone fraction produces compounds that benefit gut health, such as hydroxyphenolic acids and other derivatives [Hernández-Maldonado et al., 2019; Kim et al., 2018].

Regarding gastrointestinal infectious diseases, dietary fiber intake has been shown to help mitigate disorders, including constipation and diarrhea associated with gut microbiota changes. In addition, dietary fiber is related to bioactive components such as phenolic compounds, which are bioaccessible once released in the digestive tract [Anaya-Loyola et al., 2020; Hernández-Maldonado et al., 2019]. Thereby, diarrhea reduction can be associated with the content of gallotannins, such as penta-, hexa- and heptagalloyl glucose, in mango residues, which inhibit the growth of pathogenic microorganisms, like Campylobacter jejuni involved in acute diarrhea [Anaya-Loyola et al., 2020; Kim et al., 2018; Vazquez-Olivo et al., 2019].

In another study, a reduction in flatulence and abdominal inflammation was reported in children who consumed a beverage from mango juice residues (peel and pulp), which was constituted by dietary fiber with a high content of extractable polyphenols (mono- to heptagalloyl hexosides and mangiferin) and polyphenols released by hydrolysis [Anaya-Loyola et al., 2020]. Methyl gallate has also been demonstrated to exert antidiarrheal, spasmolytic, anti-inflammatory, and antioxidant effects in preclinical models of intestinal inflammation [Anzoise et al., 2018]. The cited authors also showed it reduced intestinal motility, decreasing peristalsis by 74.5% (100 mg/kg) and 58.82% (300 mg/kg), and observed a greater effect of the 100 mg/kg dose applied in a preclinical model with intestinal disorders.

Multiple factors are involved in the gut health, such as a balanced microbial composition, intestinal permeability, healthy epithelial barrier, and a vigorous colonic mucosa. Any disorder of these factors can cause oxidative stress and induce development of intestinal diseases, including obesity, inflammatory bowel disease, mucosal ulceration, ulcerative colitis, and Crohn’s disease [Hernández-Maldonado et al., 2019; Kim et al., 2020; Ye et al., 2022]. Particularly, inflammatory bowel disease is characterized by chronic inflammation and dysbiosis, which are the main factors for the development of gastrointestinal neoplasms or colon cancer. Worthy of mention is that 60% of stomach cancer and 43% of colon cancer are attributed to low consumption of vegetables [Anzoise et al., 2018; Kim et al., 2018; Navarro et al., 2019; Vazquez-Olivo et al., 2019].

The gut microbiota plays an important role in food digestion, immunity and other metabolic functions. The human intestinal microbial communities are defined by host genetics, intestinal dysbiosis, endogenous factors (antibiotics and xenobiotics consumption), and other environmental factors. However, dietary components play a crucial role in regulating microbial profiles, mainly fiber and phenolic compounds [Bento-Silva et al., 2020; Kim et al., 2018]. From this perspective, phenolic compounds have become relevant for health since they can modify the gut microbiota, increasing the release of metabolites with more significant bioactivity [Hernández-Maldonado et al., 2019; Kim et al., 2018]. Moreover, phenolic molecules with a higher degree of polymerization, as gallotannins, have been linked with substantial anti-inflammatory and anticancer properties [Navarro et al., 2019]. For example, Kim et al. [2020] demonstrated that gallotannins and gallic acid mitigated intestinal inflammation and carcinogenesis by intestinal microbiome modulation. Mangiferin has also been reported to improve intestinal inflammation in a murine model with induced colitis [Kim et al., 2018; Vazquez-Olivo et al., 2019]. On the other hand, Navarro et al. [2019] identified 71 compounds, including 32 gallates and gallotannins with different degrees of polymerization, 7 hydroxybenzophenone derivatives (maclurin and iriflophenone), 6 xanthonoids (isomangiferin derivatives and mangiferin), 11 phenolic acids, and 8 flavonoids (derived from rhamnetin and quercetin), when evaluating the cytotoxic effect of mango peel extracts on different human carcinoma cells related to the digestive tract, and concluded that gallotannins and xantonoids play an essential role in toxicity against cancer cells.

The mango’s phenolic compounds and their derivatives have also been noted to participate in processes linked to immune system regulation by gut microbiota modulation. For instance, using a rat model with DSS-induced colitis, Kim et al. [2020] surveyed a mango polyphenol concentrate. They found significant changes in the profiles of bacteria belonging to the Firmicutes Phylum (Lactobacillus plantarum, Lactococcus lactis, and Clostridium butyrium). Consequently, the production of short-chain fatty acids (SCFAs) was induced as butyrate and valerate. It was also observed a suppression of HDAC1 activity and an increase of AMPK activity together with levels of autophagy biomarkers; thereby, the mango phenolic compounds intake could mitigate intestinal inflammation. In addition, other studies have demonstrated that quercetin can modify the gut microbiota, improving the Bifidobacteria growth and the ratio of Firmicutes decreasing to Bacteroidetes. Interestingly, by conducting an in vitro gut simulation to evaluate a mango by-product rich in polyphenols and dietary fiber, Sayago-Ayerdi et al. [2019] detected an increase in Bifidobacterium relative abundance at 24 h and increased microbial genera diversity at 72 h, including mainly Lactobacillus, Dorea, and Lactococcus. In this sense, through a human clinical study, Kim et al. [2018] showed that mango intake encouraged the growth of Lactobacillus genera (L. plantarum, L. reuteri, and L. lactis), promoting butyrate production. Furthermore, mango consumption mitigated intestinal inflammation by decreasing the production of pro-inflammatory cytokines.