Table 1.
Modulatory effects of plant-derived (poly)phenols on the gut microbiota and their metabolic outcomes.
| (Poly)phenol | Model | Regimen | Gut Microbiota Modulation | Metabolic Outcomes | Ref. |
|---|---|---|---|---|---|
| Pre-clinical Studies | |||||
| Resveratrol | DSS-induced colitic rats |
1 mg/kg/day supplemented to the diet for 25 days. |
↑ Bifidobacterium
, ↓ Enterococcus faecalis, ↑ Lactobacillus. |
↑ food intake, ↓ body weight loss associated to the animal model. | [64] |
| HFD-fed mice | 60 mg/kg/day supplemented to the diet for 5 weeks. |
↓ Bacteroides vulgatus, ↓ Alistipes putredinis, ↓ Parabacteroides johnsonii. |
↑ glucose tolerance, ↑ GLP-1 and insulin levels, ↑ GLP-1 intestinal content. |
[65] | |
| HFD-fed mice | 200 mg/kg/day supplemented to the diet for 12 weeks. |
↑ Bacteroidetes, ↑ Bifidobacterium, ↑ Lactobacillus, ↓ Enterococcus faecalis. |
↓ body weight, ↓ abdominal adipose tissue, ↓ liver weight, ↓ glycemia, ↓ dyslipidemia. |
[66] | |
| HFD-fed mice | 200 mg/kg/day by oral gavage for 8 weeks. |
↓ Lactococcus, ↓ Oscillibacter, ↓ Clostridium XI, ↓ Flavonifractor, ↓ Hydrogenoanaerobacterium. |
↓ body weight, ↓ epididymal adipose tissue, ↑ glucose tolerance, ↑ insulin sensitivity. |
[67] | |
| HFHS-fed mice | 400 mg/kg/day supplemented to the diet for 8 weeks. |
↑ Bacteroides,
↓ Turicibacteraceae, ↓ Lachnospiraceae, ↑ Parabacteroides, ↓ Akkermansia. |
↓ fat mass, ↑ glucose tolerance. | [68] | |
| HFD-fed mice | 400 mg/kg/day supplemented to the diet for 4 weeks *. | ↑ Lactobacillus, ↑ Bifidobacterium, ↓ Proteobacteria. | ↓ body weight gain, ↑ glucose homeostasis, ↓ perigonadal and inguinal adipose tissue, ↑ white adipose tissue browning. |
[69] | |
| HFD-fed mice | 400 mg/kg/day supplemented to the diet for 16 weeks. | ↑ Erysipelotrichaceae family, ↑ Allobaculum spp. | ↓ body weight, ↓ subcutaneous and visceral adipose tissue, ↑ lean mass, ↓ food intake. |
[70] | |
| Fecal transplantation from HFD-fed RSV-treated to HFD-fed untreated mice | 300 mg/kg/day by oral gavage for 16 weeks. |
↑ Bacteroides, ↑ Lachnospiraceae, ↑ Lachnoclostridium, ↑ Parabacteroides, ↑ Ruminiclostridium, ↑ Blautia. |
↓ body weight, ↓ white adipose tissue, ↑ white adipose tissue browning, ↓ blood glucose, ↑ insulin sensitivity, ↓ hepatic steatosis, ↓ serum LPS levels. |
[71] | |
| Perinatal and post-weaning HFr-fed rats | 50 mg/L in drinking water to mothers and offspring up to 12 weeks old. |
↓ Bacteroidetes, ↑ Lactobacillus, ↑ Bifidobacterium, ↑ Akkermansia. |
↑ body weight, ↓ blood pressure, ↓ renal oxidative stress, ↑ nutrient-sensing signals. | [72]. | |
| HFD-fed mice | 60 mg/kg/day supplemented to the diet for 5 weeks. | ↓ Rikenellaceae,↑ Ruminococcaceae, ↓ Peptostreptococcaceae, ↓ Proteobacteria. | ↑ glucose tolerance. | [73] | |
| HFD-fed rats | 10 mg/kg/day supplemented to the diet for 8 weeks. | ↓ Bacteroides, ↑ Lachnospiraceae, ↓ Desulfovibrionaceae. | ↓ blood glucose, ↑ insulin sensitivity. | [74]. | |
| HFHFr-fed rats | 30 mg/kg/day supplemented to the diet for 8 weeks. | ↑ Blautia, ↑ Moryella, ↑ Lactococcus. | ↓ liver weight, ↓ hepatic transaminases levels, ↓ steatohepatitis. |
[75] | |
| Pterostilbene | Obese Zucker (fa/fa) rats | 15 mg/kg/day by oral gavage for 6 weeks. |
↑ Mollicutes, ↓ Negativicutes, ↓ Lachnospiraceae, ↓ Defluviitaleaceae, ↑ Verrucomicrobia. |
↓ body weight gain, ↓ white adipose tissue, ↓ insulin levels, ↑ insulin sensitivity. |
[76] |
| HFHF-fed rats | 15 and 30 mg/kg/day supplemented to the diet for 8 weeks. |
↓ Clostridium sensu stricto 1, ↑ Erysipelatoclostridium, ↑ Fourrnierella, ↑ Akkermansia. |
↓ hepatic transaminases levels, ↓ steatohepatitis. | [75] | |
| EGCG | Wistar rats | 300 and 600 mg/kg/day supplemented to the diet for 4 weeks *. |
↑ Bacteroides, ↓ Prevotella, ↓ Clostridium, ↓ Bifidobacterium. |
↓ liver weight, ↓ abdominal adipose tissue (higher dose). | [77] |
| ICR mice | 50, 750, or 1500 mg/kg/day supplemented to the diet for 2–10 days *. |
↓ Clostridium cluster IV, ↓ Clostridium cluster XIVa. |
↓ CYP3A gene and protein expression in the liver, ↓ pregnane X receptor (PXR) protein expression in the liver (higher dose). | [78] | |
| HFD-fed mice | 320 mg/kg/day (roughly) supplemented to the diet for 8 weeks *. |
↑ Allobaculum, ↑ Clostridium, ↑ Parabacteroides, ↓ Lachnospiraceae, ↓ Ruminococcous, ↑ Adlercreutzia, ↓ Desulfovibrionaceae, ↑ Akkermansia. |
↓ body weight, ↓ hepatic steatosis, ↓ hepatic TG, ↓ serum non-esterified fatty acids. |
[79] | |
| Quercetin | HFD-fed mice | 50 mg/kg/day aglycone quercetin supplemented to the diet for 16 weeks *. |
↑ Bacteroidia,↑ Erysipelotrichi, ↓ Bacilli, ↓ Clostridia, ↓ Helicobacter, ↑ Betaproteobacteria, ↓ Desulfovibrio, ↓ Deltaproteobacteria, ↑ Akkermansia. |
↓ body weight gain, ↓ epididymal fat pads, ↓ glycemia, ↓ insulinemia, ↑ insulin sensitivity, ↓ plasma TG, ↓ plasma alanine aminotransferase activity, ↓ hepatic steatohepatitis. |
[80] |
| Hesperetin | Wistar rats | 500 mg/kg/day supplemented to the diet for 3 weeks *. |
↓ Clostridium subcluster XIVa, ↑ Clostridium clusters IV, XVIII. |
↓ abdominal adipose tissue. | [81] |
| Theaflavins | db/db mice | 100 mg/kg/day supplemented to the diet for 7 weeks *. |
↓ Barnesiella, ↓ Odoribacter, ↓ Lachnospiraceae, ↓ Desulfovibrio. |
↓ insulinemia. | [82] |
| Sinapine | HFD-fed mice | 500 mg/kg/day supplemented to the diet for 12 weeks *. |
↑ Prevotellaceae,↑ Lactobacillaceae, ↓ Lachnospiraceae, ↓ Erysipelotrichaceae, ↓ Peptostreptococcaceae, ↑ Blautia, ↑ Bifidobacterium, ↑ Eggerthellaceae, ↓ Desulfovibrio, ↑ Akkermansiaceae. |
↓ body weight, ↓ food efficiency, ↓ white adipose tissue, ↓ blood glucose, ↓ plasma TG, ↓ plasma LDL-C, ↓ insulinemia, ↑ insulin sensitivity, ↓ hepatic steatosis. |
[83] |
| Hydroxytyrosol | Fine particulate matter-exposed mice | 50 mg/kg/day by oral gavage for 4 weeks. | ↑ Bacteroidetes, ↑ Akkermansia. | ↓ visceral adipose tissue, ↑ glucose tolerance, ↑ insulin sensitivity, ↓ hepatic oxidative stress, ↓ hepatic inflammation. |
[84] |
| HFD-fed mice | 50 mg/kg/day by oral gavage for 8 weeks. | Unchanged Bacteroidetes/Firmicutes. | ↓ white adipose tissue, ↓ liver weight, ↓ blood glucose, ↑ insulin sensitivity, ↓ hepatic steatosis, ↓ plasma LPS. |
[85] | |
| Capsaicin | HFD-fed mice | 2 mg/kg/day supplemented to the diet for 12 weeks *. |
↓ LPS-producing S24-7 family, ↑ Ruminococcaceae, ↑ Lachnospiraceae. |
↓ body weight gain, ↓ white adipose tissue, ↑ glucose tolerance, ↓ serum LPS, ↓ serum proinflammatory cytokines. |
[86] |
| HFD-fed mice | 10 mg/kg/day supplemented to the diet for 9 weeks *. | ↑ Bacteroides, ↑ Prevotella, ↑ Coprococcus, ↑ Akkermansia, ↓ Proteobacteria, ↑ Acidobacteria. | ↓ body weight gain, ↓ food intake, ↑ glucose tolerance. | [87] | |
| ob/ob mice | 6 and 12 mg/kg/day supplemented to the diet for 6 weeks *. | ↓ Bacteroides, ↑ Roseburia, ↑ Parabacteroides. | ↑ glucose tolerance, ↑ insulin sensitivity. | [88] | |
| db/db mice | 10 mg/kg/day added to the diet for 4 or 8 weeks *. | ↓ Lactobacillus. | ↓ blood glucose, ↓ insulinemia, ↑ glucose tolerance, ↑ insulin sensitivity. | [89] | |
| HFD-fed TRPV1−/− mice | 2 mg/kg/day by oral gavage for 12 weeks. |
↑ Bacteroides, ↑ Prevotella, ↓ endotoxemic S24-7 family, ↑ Coprococcus, ↓ Actinobacteria, ↓ Desulfovibrio, ↓ Escherichia, ↓ Helicobacter, ↓ Sutterella, ↑ Akkermansia, ↓ Cyanobacteria, ↑ Tenericutes. |
↓ body weight gain, ↓ food intake, ↓ blood glucose, ↓ plasma TG, TC, and LDL-C, ↓ insulinemia. | [90] | |
| Dihydrocapsiate | HFD-fed mice | 2 and 10 mg/kg/day by oral gavage for 12 weeks. | No change in Lactobacillus, Bifidobacterium, and Akkermansia. | ↓ plasma TG, ↓ insulinemia, ↑ glucose tolerance, ↓ hepatic steatosis. |
[91] |
| Honokiol | HFD-fed mice | 200, 400 and 800 mg/kg/day supplemented to the diet for 8 weeks. |
↑ Bacteroides, ↓ Muribaculaceae, ↓ Oscillospira, ↓ Ruminococcus, ↓ Lactococcus, ↓ Dehalobacterium, ↓ Unclassified_Clostridiales, ↓ Unclassified_Ruminococcaceae, ↑ Unclassified_Enterobacteriaceae, ↑ Bilophila, ↑ Akkermansia, ↑ Fusobacterium. |
↓ body weight, ↓ white adipose tissue, ↓ serum TG, and TC, ↓ serum free fatty acids, ↓ blood glucose. | [92] |
| Clinical Studies | |||||
| Trans-resveratrol | MetS humans | 2 g/day orally for 30 days. |
↓ Rikenellaceae, ↓ Butyricimonas, ↑ Gemellaceae, ↑ Turicibacter, ↓ Ruminococcus, ↓ Oscillospira, ↓ Clostridium, ↓ Odoribacter, ↓ Alistipes, ↑ Gammaproteobacteria, ↑ Akkermansia, ↑ Atopobium. |
↑ glucose tolerance in Caucasian subjects only. | [93] |
| Trans-resveratrol + EGCG | Overweight humans |
80 mg/day RVS and 282 mg/day EGCG orally for 12 weeks. |
↓ Faecalibacteriuim prausnitzii, ↓ Bacteroidetes (only in men). |
↑ skeletal muscle mitochondrial oxidative capacity, ↑ increased fat oxidation. | [94] |
| Capsaicin | Humans | 0.078 mg/kg/day for 2 weeks, 1 week washout and then 0.156 mg/kg/day for 2 weeks *. | ↑ Lachnospiraceae, ↑ Ruminococcaceae, ↑ Faecalibacterium. | ↑ plasma GLP-1, ↑ GIP and ghrelin. | [95] |
Phyla to which mentioned bacteria families, genera or species pertain to are color-coded as: Bacteroidetes (blue), Firmicutes (red), Actinobacteria (purple), Proteobacteria (orange), Verrucomicrobia (green), and others (black). Abbreviations: DSS—dextran sulfate sodium; GLP-1—glucagon-like peptid-1; GIP—gastric inhibitory polypeptide; TG—triglyceride; TC—total cholesterol; HDL-C—high density lipoprotein cholesterol; LDL-C—low density lipoprotein cholesterol; HOMA—homeostatic model assessment; CYP3A—enzyme cytochrome P450 3A; LPS—lipopolysaccharide; MetS—metabolic syndrome; HFr—high fructose diet; HFD—high fat diet; HFHFr—high fat/high fructose; HFHS—high fat/high sugar; EGCG—epigallocatechin-3-gallate. ↑, implies increased levels or improved function; ↓, implies decreased levels or impaired function; *, implies that dose values were estimated from the consumption of the (poly)phenol-containing diet.