Table 1.

Beneficial effects of polyphenols in metabolic disorders in relation to the gut microbiota in high-fat diet (HFD)-fed murine models.

Reference, Publication Year, Animal Species, Polyphenol(s), and Dosage	Major Physiological Issues Improved	Mode of Action
		Antioxidative and Anti-Inflammatory Action	Gut Microbiota Modulation
[12] 2013 Mice, polyphenol-rich pomegranate peel extract (PPE), p.o. in drinking water containing 0.2% PPE (average consumption of 6 mg/d per mouse) for 4 weeks	Reduced serum cholesterol (total and LDL) levels and alleviated tissue (colon and visceral adipose tissue) inflammation	−	Promoted the growth of gut bacteria, in particular, Bifidobacterium spp.
[13] 2014 Rats, p.o. as instant caffeinated coffee at a concentration of 20 g/L for 8 weeks (HFD was given for 10 weeks)	Reduced weight gain, adiposity, liver triglycerides, and energy intake	−	Decreased the Firmicutes/Bacteroidetes ratio
[14] 2015 Mice, high fat/high sucrose diet (HFHSD), polyphenol-rich cranberry extract, p.o. at 200 mg/kg/day for 8 weeks	Reduced visceral obesity and improved insulin sensitivity	Ameliorated oxidative stress and inflammation in the jejunum and reduced circulating LPS	Increased the relative abundance of Akkermansia spp.
[15] 2016 Mice, extractable polyphenol-rich fraction of table grapes (EP), p.o. with diet containing 1.1 g EP/kg for 16 weeks	Reduced white adipose tissue mass and improved glucose tolerance	−	Partially restored the HFD-mediated reduction in diversity
[16] 2016 Mice, green tea polyphenols (GTP), p.o. with a diet containing 0.05, 0.2, and 0.8% GTP for 8 weeks	Reduced obesity, and improved hepatic steatosis	−	Partially restored the HFD-mediated reduction in diversity
[17] 2017 Rats, a combination of quercetin (Q) and resveratrol (R), p.o. at 30 mg Q + 15 mg R/kg/day for 8 weeks	Reduced obesity	Attenuated serum inflammatory markers	Decreased the Firmicutes/Bacteroidetes ratio
[18] 2017 Mice, p.o. polyphenol- and caffeine-rich post-fermented Pu-erh tea, p.o. at 750 mg/kg/day for 12 weeks	Improved glucose and lipid metabolism disorder	Attenuated expression of inflammation genes in the proximal colon, reduced circulating LPS, and restored gut barrier integrity	Restored the HFD-induced gut microbial community structural shift
[19] 2018 Mice, polyphenol-rich cinnamon bark, or grape pomace extract (CBE or PBE), p.o. with a diet containing 0.2% CBE or and 0.8% PBE for 8 weeks	Reduced fat mass gain and adipose tissue inflammation, and ameliorated liver steatosis	Reduced adipose tissue inflammation, and improved gut barrier function	Decreased abundance of Desulfovibrio and Lactococcus at the genus level
[20] 2018 Mice, Lonicera caerulea L. berry polyphenols (LCBP), p.o. with diet containing 0.5% and 1% LCBP for 45 days	Improved hepatic steatosis	Attenuated serum inflammatory markers, and decreased LPS level in serum and liver	Decreased the Firmicutes/Bacteroidetes ratio
[21] 2019 Rats, resveratrol (RSV) and sinapic acid (SA), p.o. at 400 mg RSV/kg/day, 200 mg SA/kg/day, or a combination of RSV and SA for 8 weeks	Reduced fasting blood glucose levels and increased HDL-C levels by RSV	Decreased ROS and MDA levels in the colon, and increased total antioxidant capacity in the liver by SA	Combination of RSV and SA: Improved proportion of butyrate producer Blautia and Dorea from the Lachaospiraceae family and inhibited growth of bacterial species associated with diseases and inflammation, such as Bacteroides and Desulfovibrionaceae sp.
[22] 2019 Rats, sinapine (a rapeseed polyphenol), p.o. at 500 mg/kg/day for 12 weeks	Ameliorated NAFLD, reduced body weight and decreased TG and LDL-C levels.	Suppressed expression of NF-κB and TNF-α in the intestine and enhanced expression of IRS-1 in the adipose tissue	Decreased Firmicutes/Bacteroidetes ratio and increased abundance of probiotics, along with SCFA-mediated upregulation of G protein-coupled receptor 43 (GPR43) to inhibit the expression of inflammatory factors
[23] 2019 Mice, tea polyphenols (TPs) including EGCG, EGC, and ECG, p.o. at 100, 200, and 400 mg/kg/day for 12 weeks	Ameliorated hyperlipidemia, enhanced expression levels of hepatic lipid metabolism genes, and modulated gut microbiota	Maintenance of intestinal redox state by TPs	Decreased gut microbiota diversity and relative abundance of Proteobacteria, a source of LPS, possibly due to the antimicrobial activity of TPs
[24] 2019 Rats (treated with HFD + STZ), polyphenol-rich extracts from brown macroalga Lessonia trabeculata containing phlorotannin derivatives, phenolic acid derivatives, and gallocatechin derivatives, p.o. at 200 mg/kg/day for 4 weeks	Lowered fasting blood glucose and insulin levels, as well as better serum lipid profiles and antioxidant stress parameters	Increased response of antioxidant defense systems (e.g., CAT, SOD, and GSH in the liver) to oxidative stress	A positive effect on regulating the dysbiosis of the microbial ecology in diabetic rats
[25] 2019 Mice, pomegranate peel polyphenols including gallic acid, punicalagin, and catechin, p.o. at 150 and 300 mg/kg/day for 12 weeks	Alleviated obesity, decreased circulating proinflammatory cytokines, colonic tissue damage, and enhanced protein expression in the colonic tight junction	Improved oxidative damage and inflammation of the intestinal tissues, thereby reversing the reduced levels of tight junction proteins	Normalized the HFD-induced gut microbiota imbalance by increasing the abundance of beneficial bacteria in the colon
[26] 2020 Mice [fecal microbiota transplantation (FMT) to HFD-fed mice], resveratrol (RSV), p.o. at 300 mg/kg/day for 16 weeks followed by transplantation of the RSV-microbiota to HFD-fed mice (HFD-RSVT) to explore the function of the microbiota	HFD-RSVT decreased weight gain and increased insulin sensitivity	HFD-RSVT reduced the production of ROS and MDA in the intestine	A remarkable alteration in the composition of gut microbiota in mice treated with RSV, for example, enrichment of Bacteroides, Lachnospiraceae_NK4A136_ group, Blautia, Lachnoclostridium, Parabacteroides, and Ruminiclostridium_9, collectively referred to as RSV-microbiota
[27] 2020 Rats, Lonicera caerulea L. polyphenols containing anthocyanins, phenolic acids, and flavonoids, p.o. at 250 mg/kg/day for 8 weeks	Ameliorated intestinal permeability and intestinal inflammation; alleviated LPS-induced liver injury	Ameliorated intestinal oxidative stress damage (through regulation of the Nrf2/HO-1/NQO1 pathway)	Increased relative abundance of Bacteroidetes and Tenericutes and decreased relative abundance of Proteobacteria at the phylum level
[28] 2020 Mice (FMT from HFD-fed mice to HFD-fed mice), resveratrol (RSV), p.o. at 300 mg/kg/day for 16 weeks followed by transplantation of the HFDR-microbiota to HFD-fed mice (HFD-RSVT)	Alleviated NAFLD; ameliorated liver oxidative stress by HFD + RSV-microbiota treatment	HFD + RSV-microbiota treatment prevented HFD-induced production of ROS and improved antioxidant defense mechanisms (SOD and GSH levels)	The RSV-induced gut microbiota characterized by a decreased abundance of harmful bacteria, including Desulfovibrio, Lachnospiraceae_NK4A316_group, and Alistipes, as well as an increased abundance of SCFA-producing bacteria, such as Allobaculum, Bacteroides, and Blautia
[29] 2020 Mice, resveratrol (RSV), p.o. at 300 mg/kg/day for 16 weeks	Improved obesity	A two-part anti-obesity mechanism of RSV through the gut microbiota was proposed:(1) improved composition and function of the gut microbiota as well as the intestinal oxidative state; (2) 3-hydroxyphenylpropionic acid and 4-hydroxyphenylacetic acid (biotransformed from RSV by the gut microbiota), which may be responsible for the beneficial effects of RSV
[30] 2020 Rats, polyphenol extracts from Shanxi-aged vinegar containing at least 41 polyphenols (including 18 phenolic acids), p.o. at 4, 8, and 16 mg/kg/day for 4 weeks	Improved hyperlipidemia	Improved inflammatory stress- and oxidative stress-related indicators	Decreased the Firmicutes/Bacteroidetes ratio; increased the diversity of microorganisms
[31] 2021 Mice, resveratrol (RSV) with probiotic Bifidobacteria, p.o. at 100 mg RSV/kg/day and probiotic Bifidobacteria for 3 weeks, starting the fifth week of HFD feeding	Coadministration of B. longum and RSV alleviated obesity and NAFLD	The combination of B. longum and RSV exerted an inhibitory effect on inflammatory cytokines and increased the levels of antioxidants, including SOD and GSH, and decreased the levels of MDA	RSV acted as an excellent prebiotic because most orally administered RSV is located in the bowel lumen
[32] 2021 Mice, Capsicum annuum L. ‘Senise’ extract (CAE) containing polyphenols, lycopene, and capsinoid derivatives, p.o. at 1, 10, and 25 mg/kg/day for 6 weeks	Promoted weight loss and improved plasma markers related to glucose and lipid metabolism	Reduced the expression of proinflammatory cytokines possibly due to the antioxidant property of CAE	Decreased the Firmicutes/Bacteroidetes ratio
[33] 2021 Rats, polyphenol-rich whole red grape juice, p.o. at 10 mL/day + physical training for 60 days	Lowered the concentration of IL-6 and TBARS	Reduced oxidative stress by activating the body’s antioxidant system, preventing the action of free radicals, and consequently, reducing the expression of inflammatory cytokines	The juice consumption beneficially modulated the gut microbiota
[34] 2021 Rats, Fu brick tea polyphenols, including EGCG, EGC, and ECG, p.o. at 100 mg/kg for 12 weeks	Improved the intestinal oxidative stress and intestinal barrier function, including intestinal inflammation and the integrity of the intestinal barrier		Attenuated HFD-induced gut microbiota dysbiosis, characterized by increased phylogenetic diversity and decreased Firmicutes/Bacteroidetes ratio

p.o., per os; ROS, reactive oxygen species; MDA, malondialdehyde; NAFLD, nonalcoholic fatty liver disease; NF-κB, nuclear factor-kappa B; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; IRS-1, insulin receptor substrate 1; EGCG, epigallocatechin gallate; EGC, epigallocatechin; ECG, epicatechin gallate; SCFA, short-chain fatty acid; LPS, lipopolysaccharide; STZ, streptozotocin; CAT, catalase; SOD, superoxide dismutase; GSH, glutathione; Nrf2, nuclear factor (erythroid-derived 2)-like 2; HO-1, heme oxygenase 1; NQO1, quinone oxidoreductase 1; FMT, fecal microbiota transplantation; IL-6, interleukin-6; TBARS, thiobarbituric acid-reactive substances; ―, not clearly described.