Table 1.
The regulatory effect of flavonoids on the gut microbiota.
| Compounds | Model/Material | Dosage form | Major findings | References |
|---|---|---|---|---|
| Flavonols | ||||
| Quercetin | HFD Ldlr−/− C57BL/6 mice | Oral administration of quercetin (100 μg day−1) supplement diets | Oral quercetin treatment suppressed the abundance of Verrocomicrobia and increased the abundances of Actinobacteria, Cyanobacteria, and Firmicutes, as well as microbiome diversity | (86) |
| HFD male C57BL/6J mice divided into gut microbiota donor and receiver | Supplement diets with aglycone quercetin (0.05% wt/wt) at a dosage roughly equal to 80 mg kg−1 day−1 | The notable increase of Verrucomicrobia phylum, Verrucomicrobiae class, and Akkermansia genu proved the prebiotic capacity of quercetin in gut microbiota transferring from donor to receiver mice model | (87) | |
| High-fat sucrose diet (HFS) Wistar rats | Feeding quercetin (30 mg/kg−1 day−1) as a supplement | Quercetin supplementation inhibited the growth of bacterial species previously associated with diet-induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium cylindroides) | (85) | |
| Male APP/PS1 transgenic mice (B6C3F1) | Supplement with 0.08% quercetin roughly equal to 120 mg kg−1 d−1 in modified AIN-93G diet | Under low vitamin D status, quercetin elevated gut microbial diversity (including Facklamia and Aerococcus), and improved cognitive function | (90) | |
| Pseudomonas aeruginosa strain PAO1 | PAO1 was cultured with quercetin (16 μg/ml) | Quercetin inhibited Pseudomonas aeruginosa by the factors of quorum sensing, biofilm formation, and virulence | (96) | |
| Staphylococcus aureus | Alnus japonica extracts at 0.1 mg ml−1 | Quercetin influenced quorum sensing hence acted as an anti-biofilm compound against S. aureus | (97) | |
| Ten enteric bacteria and murine macrophage-like RAW264 cells | Quercetin dissolved in DMSO with final 25 μM in 1 ml of serum | Several flavonols like quercetin have a prebiotic-like effect on promoting B. adolescentis exerting anti-inflammatory activity by producing produces NO inhibitors | (81) | |
| Probiotic Lactobacillus rhamnosus, Salmonella typhimurium, and Caco-2 cells | Quercetin at a final concentration of 2 mg/ml | Quercetin could inhibit gut pathogen Salmonella typhimurium growth and adhesion to a human gut cell line, enhancing the probiotic L. rhamnosus proliferation, and adhesion | (82) | |
| Kaempferol | Collagen-induced arthritis (CIA) model mice | Treating mice with kaempferol intragastrically (200 mg · kg−1 · d−1) and intraperitoneally (20 mg · kg−1 · d−1) | The high level of kaempferol produced distinct anti-arthritis effects in CIA model mice and regulated the intestinal flora and microbiotic metabolism | (98) |
| Helicobacter pylori and human AGS cell ATCC® CRL-1739 | The minimal inhibitory concentration (MIC) of kaempferol against H. pylori was 50 μM | Kaempferol suppressed Helicobacter pylori vacuolating cytotoxin A and cytotoxin-associated gene A translocation to AGS cells | (83) | |
| Escherichia coli | The MIC of kaempferol was 25 μg/ml | Kaempferol could have great anti-Escherichia coli activity and inhibition of DNA gyrase | (99) | |
| Myricetin | — | — | The review summarized myricetin preclinical pharmacological activities, including antimicrobial properties with multiple mechanisms | (100) |
| S. aureus infection Galleria mellonella model | Myricetin at 200 μM | Myricetin possessed the influence on several factors by S. aureus, including adhesion, biofilm formation, and staphyloxanthin production | (101) | |
| Flavones | ||||
| Apigenin | — | — | The review summarized studies on antimicrobial effects of apigenin as well as the relationship between apigenin and human gut microbiota | (102) |
| Human gut microbiota preparation from healthy female | Apigenin at 5, 12.5, 25, 50, and 100 μg/ml | Apigenin effectively inhibited the growth of both Enterococcus caccae and Bacteroides galacturonicus on a single strain; on the contrary, it enhanced the growth of Enterococci in the community | (103) | |
| Baicalein | Lactobacillus rhamnosus JB3, human AGS cell ATCC® CRL-1739 and male C57BL/6 Helicobacter pylori infections mice | Baicalein at the concentrations of 1, 0.5, 0.25, 0.125, and 0.0625 mM | Baicalein and Lactobacillus spp. had a synergistic effect on eradicating Helicobacter pylori infections in vitro and in vivo | (84) |
| SAMP8 mice | Administration baicalein with 200 mg kg−1 d−1 | Baicalein altered the abundance of six genera in SAMP8 mice, reducing Mucispirillum, Parabacteroides, Bacteroides, and Sutterella, in contrast, increasing Christensenellaceae | (104) | |
| Male Wistar rats to establish high-fat, high-sugar diet (HFHSD) rat model | Baicalein at 50 mg kg−1 d−1 | Baicalein could modulate the composition of gut microbiota via influence on the abundance of beneficial and pathogenic bacteria | (88) | |
| Chrysin | Male CD Sprague-Dawley rats induced by fructose to establish metabolic syndrome model | Chrysin at 100 mg kg−1 d−1 | Chrysin could affect fructose inducing rats intestinal microbiome, especially increasing Firmicutes to Bacteroidetes ratio | (105) |
| Isoflavones | ||||
| Genistein | HFD male C57BL/6J mice | HFD with 0.2% genistein approximately 3 mg kg−1 d−1 | The abundance among the Prevotella and Akkermansia genera, particularly Prevotella copri and Akkermansia muciniphila under the treatment of genistein | (89) |
| Female non-obese diabetic (NOD) mice | Oral administration of genistein at 20 mg kg−1 d−1 | Perinatal genistein exposed NOD mice exhibited an increased level of Enterobacteriales that suggested a pro-inflammatory response | (91) | |
| Germ-free RAG2−/− athymic female mice established breast cancer orthotopic xenografts | Feeding a special corn oil customized diet (genistein-0.25 g/Kg) | In the genistein-treated humanized mice, the abundance of genera Lactococcus and Eubacterium increased | (106) | |
| Flavan-3-ols | ||||
| Epicatechin | —— | —— | This review introduced four main catechins found in green tea, including (–)-epicatechin (EC), (–)-epicatechin-3-gallate (ECG), (–)-epigallocatechin (EGC), and (–)-epigallocatechin-3-gallate (EGCG), had antimicrobial effects, such as damage to the cell membrane, inhibition of enzyme activity | (107) |
| Lactobacillus acidophilus strains KCTC 3140, KCTC 3146, KCTC 3154, and KCTC3179 | Epicatechin was quantified as 6.36 μg/ml in the Bulnesia sarmienti aqueous extracts | (–)-Epicatechin from Bulnesia sarmienti aqueous extract as the prebiotic active components enhanced the growth of four Lactobacillus acidophilus isolated from rat, pig, chicken, and human gut | (108) | |
| Gallocatechin | Cystic Fibrosis patients fecal samples with ingesting flavonoid | —— | Gallocatechin was found to be correlated with the family Actinomycetaceae (Actinobacteria) | (109) |
| Flavanones | ||||
| Naringenin | Ruminococcus gauvreauii, Bifidobacterium catenulatum, and Enterococcus caccae | Naringenin in a final concentration of 200, 150, 100, and 50 μg/ml in strain-specific broth containing 1% DMSO | Naringenin had the effect on the growth and genetic expression of three gut microbes, with the result of increasing Bifidobacterium catenulatum, inhibiting Enterococcus caccae, and no affection to Ruminococcus gauvreauii, both changing to the gene expression for all three strains | (110) |
| Escherichia coli O157:H7 ATCC 43895 and Vibrio harveyi MM32 | Naringenin at 6.25, 12.5, 25, 50, and 100 μg/ml | Naringenin had the potential to be a inhibitor of autoinducer-mediated cell–cell signaling for modulating the Escherichia coli biofilm and Vibrio harveyi MM32 virulence | (111) | |
| Eriodictyol | S. aureus USA300 strain ATCC BAA-1717 and human alveolar epithelial cell line (ATCC CCL185) | The MIC of eriodictyol against S. aureus was 512 μg/mL | Eriodictyol had the potential against S. aureus infection via downregulating alpha-hemolysin at the levels of expression and transcription | (112) |
| Anthocyanins | ||||
| Malvidin-3-glucoside | C57BL/6J male mice induced by DSS | The AIN-93M containing malvidin-3-glucoside at 24 mg kg−1 diet | Malvidin-3-glucoside reduced the abundance of pathogenic bacteria, such as Ruminococcus gnavus, and restored the Firmicutes/Bacteroidetes ratio | (113) |
| Health human fecal samples | Malvidin-3-glucoside was inoculated at 20 mg/L and 200 mg/L | Malvidin-3-glucoside tested significantly enhancing the growth of Bifidobacterium spp. and Lactobacillus-Enterococcus spp. | (114) | |
| Cyanidin-3-O-glucoside | Male Wistar rats induced by 3-chloro-1,2-propanediol | The diet with supplementation of 500 mg/kg cyanidin-3-O-glucoside | Cyanidin-3-O-glucoside was found to increase the relative abundance of Lachnospiraceae and Actinobacteria and might have beneficial regulating the communities of gut microbiota | (115) |