Table 2.

Summarized roles of quercetin in enhancing intestinal immunity and gut health in human and animal models.

Subject	Design	Main Findings	References
The LDL receptor-deficient mouse C57BL/6 mice (90 days old; (24.76 ± 0.37 g)	Mice were randomly assigned to either the quercetin treatment (100µg/d; n = 12) or the control group (n = 12) and fed regular chow diet for 4 weeks, followed by a high-fat diet until 12 weeks.	Quercetin treatment to high-fat-diet-fed mice attenuated atherosclerotic lesions, elicited protective effects against immune/inflammatory responses and oxidative stress, and decreased intestinal lipid levels. Additionally, quercetin altered the gut microbiota composition by decreasing the abundance of Verrocomicrobia but increased microbiome diversity and the abundances of Actinobacteria, Cyanobacteria, and Firmicutes. Quercetin reduced the lipid level, areas of atherosclerotic lesions and sizes of plaques.	[124]
C57BL/6 mice	Dietary quercetin (30 mg/kg) was supplemented to a Citrobacter rodentium-induced colitis mouse model for 2 weeks.	Quercetin alleviated Citrobacter rodentium-induced colitis by suppressing pro-inflammatory cytokines production and modified the gut microbiota by increasing Bacteroides, Bifidobacterium, Lactobacillus, and Clostridia populations but reduced Fusobacterium and Enterococcus spp.	[125]
Broiler chickens (n = 240)	Chickens were randomized into four groups: saline-challenged; LPS-challenged; and LPS-treated broiler chickens, fed either 200 or 500 mg/kg of quercetin.	Quercetin alleviated LPS-induced oxidative stress via the MAPK/Nrf2 signaling in the intestines of chickens. Quercetin alleviated LPS-induced decrease in duodenal, jejunal, and illeal villus height and increased the crypt depth of these regions. Further, quercetin inhibited LPS-induced jejunal oxidative stress and relieved jejunal mitochondria damage.	[126]
Finishing pigs ((Large White × Landrace); n = 170; initial body weight of 72 ± 4 kg)	Pigs were randomly assigned to either a control group fed basal diet or treatment group consuming the same diet supplemented with 25 mg/kg feed quercetin, and after a 4-week period, pigs were transported for 5 h.	Quercetin-supplementation improved intestinal health and alleviated intestinal injury during transport through decreased serum endotoxin levels, lowered intestinal ROS and MDA, and lowered jejunal inflammatory cytokines expression, but increased jejunum villi height and upregulated the mRNA expression of occludin and zonula occudens-1 in the jejunum.	[127]
Male Wistar rats (8 weeks old; 250 ± 20 g)	Post-inflammatory irritable bowel syndrome (PI-IBS) model rats were administered quercetin by gavage at doses of 5, 10, and 20 mg/kg for 14 d.	Quercetin elicited an analgesic effect on PI-IBS and decreased the visceral pain threshold of PI-IBS rats, and the abdominal motor response to colon distension was markedly increased. Quercetin also reduced the colonic expression of genes responsible for enteroendocrine cell differentiation.	[128]
Rats	Rats were grouped as osteoarthritis-induced model, quercetin-treated, and control groups. Quercetin group received daily intragastric administration (100 mg/kg/d, i.g.) from day 1 to day 28.	Quercetin partially abrogated intestinal flora disorder and reversed fecal metabolite abnormalities. Diversity in the gut microbiota was decreased after quercetin treatment and at the genus level, Lactobacillus was increased whereas, unidentified Ruminococcaceae was decreased.	[129]
Ross 308 chicks (n = 128 chicks; 41 gm/chick)	Quercetin was fed to groups of broiler chickens at concentrations of 200, 400, and 800 ppm, and a control group was supplemented with a basal diet.	Dietary quercetin improved the gut microbiota environment by decreasing total coliforms and Clostridium perfringens population but increased the Lactobacillus counts. Further, the intestinal mRNA expression of intestinal Cu/Zn-superoxide dismutase, glutathione peroxidase, and nutritional transporters was upregulated in quercetin-supplemented groups.	[130]
C57BL/6J mice	Monosodium glutamate (MSG)-treated mice were randomly divided into two groups: MSG group and quercetin group (5 mg/kg quercetin) administrated by gavage at a dose of 100 µL/10 g/body weight (BW)/ d for 6 weeks.	Dietary quercetin attenuated MSG-induced gut microbiota dysbiosis and improved intestinal barrier function. Quercetin reversed MSG-induced elevation in Firmicutes abundance and decreased the Firmicutes/Bacteroidetes ratio. Further, Lachnospiraceae and Ruminicoccaceae abundance was reduced. Colon damage was recovered and Muc2 and ZO-1 expression was upregulated after quercetin treatment.	[131]
Wistar rats (n = 23)	Wistar rats were randomized into four groups fed a high-fat sucrose diet supplemented or not with trans-resveratrol (15 mg/kg body weight (BW)/d), quercetin (30 mg/kg BW/d), or a combination of both polyphenols.	Quercetin supplementation eliminated gut dysbiosis by attenuating Firmicutes/Bacteroidetes ratio and inhibited the growth of bacterial species associated to diet-induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium cylindroides).	[28]
Male C57BL/6J mice (7 weeks old)	Mice were challenged with high-fat diet (HFD) supplemented or not with quercetin (0.05% (wt/wt) aglycone quercetin) for 16 weeks.	Quercetin alleviated obesity-associated NAFLD via its anti-inflammatory, antioxidant, and prebiotic integrative response. Quercetin reverted gut microbiota imbalance and related endotoxemia-mediated TLR-4 pathway induction, with subsequent inhibition of inflammasome response and reticulum stress pathway activation.	[123]
Kunming male mice (n = 36; 18–20 g)	Mice were administrated 0.5 mL/d antibiotics cocktail intragastrically for 7 d to induce gut dysbiosis. Quercetin-treated mice were fed AIN-93G diet containing 0.2% quercetin for 10 d.	Quercetin supplementation combated gut dysbiosis since it recovered intestinal barrier function and improved the diversity of the gut bacterial community in antibiotic-treated mice. Intestinal villi length and mucosal thickness were increased and butyrate production was enhanced in quercetin-treated mice.	[120]
Sprague–Dawley rat (6 weeks old; male; 160−200 g)	Quercetin (50 mg/kg/d) was dissolved in distilled water and administered daily by gavage at 10 mL/kg for 12 weeks to streptozotocin (STZ)-induced diabetic peripheral neuropathy (DPN) rats.	Quercetin exerted a neuroprotective effect and modulated gut microbiota associated with DPN phenotypes and ROS production in STZ-induced DPN rats. Quercetin rescued gut dysbiosis by decreasing four potential pathogenic species and enriching two prebiotic species associated with DPN phenotypes and ROS production.	[132]