Phytochemicals That Influence Gut Microbiota as Prophylactics and for the Treatment of Obesity and Inflammatory Diseases

Table 1

Effects of different phytochemicals on GM and/or obesity with anti-inflammatory actions.

Phytochemicals	Compound	Model	Effect on gut microbiota	Antioxidant and anti-inflammatory effect	Effect on obesity	Ref
Polyphenols		C57BL/6 J ApcMin mice	Bacterial diversity was higher in the bilberry group than in the other groups	Attenuation of inflammation in cloudberry-fed mice		[183]
Flavonones	Baicalein	C57BL/6 J mice		Suppress activation of NF-κB and decrease expression of iNOS and TGF-β	Activation of AMPK pathway and suppression of fatty acid synthesis, gluconeogenesis, and increased mitochondrial oxidation	[184]
Catechins	Epigallocatechin-3-gallate	C57BL/6 J mice	The Firmicutes/Bacteroidetes ratio is significantly lower in HFD + EGCG but higher in control diet + EGCG		Potential use for prevention, or therapy, for obesity-related and oxidative stress-induced health risks	[185]
	Epigallocatechin-3-gallate	C57BL/6 J mice	Regulates the dysbiosis and maintains the microbial ecology balance		Significant protective effect against obesity induced by high-fat diet (HFD)	[186]
	Epigallocatechin-3-gallate	Wistar rats	EGCG affects the growth of certain species of GM		Weights of abdominal adipose tissues fed 0.6% EGCG diet were suppressed. Regulated energy metabolism in the body	[187]
	Quercetin	C57BL/6 J mice	An increase in Firmicutes/Bacteroidetes ratio and in gram-negative bacteria and increased in Helicobacter by HFD. Quercetin treatment benefits GM balance	Quercetin reverted dysbiosis-mediated Toll-like receptor 4 (TLR-4) NF-κB signaling pathway activation and related endotoxemia, with subsequent inhibition of inflammasome response and reticulum stress pathway activation	Benefits gut-liver axis activation associated to obesity, leading to the blockage of lipid metabolism gene expression deregulation	[109]
	Quercetin	Wistar rats	Quercetin supplementation attenuates Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet-induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium cylindroides). Quercetin was effective in lessening high-fat sucrose diet-induced GM dysbiosis			[188]
	Quercetin	Fischer 344 rats	Exerts prebiotic properties by decreased pH, increased butyrate production, and altered GM		Onion extract increased glutathione reductase (GR) and glutathione peroxidase (GPx1) activities in erythrocytes. In contrast, g-glutamate cysteine ligase catalytic subunit gene expression was upregulated	[189]
	Kaempferol	3 T3-L1 adipocytes		Kaempferol reduced LPS proinflammatory action. Demonstrating the anti-inflammatory and antioxidant effects	Concomitantly, polyphenols increased the production of adiponectin and PPARγ, known as key anti-inflammatory and insulin-sensitizing mediators	[110]
Anthocyanins		C57BL/6 J mice	Feces of GM-deficient mice showed an increase in anthocyanins and a decrease in their phenolic acid metabolites, while a corresponding increase was observed in jejunum tissue		Mice with intact GM reduced body weight gain and improved glucose metabolism	[190]
Anthocyanins		C57BL/6 J mice		Anthocyanins could effectively reduce the expression levels of IL-6 and TNFα genes, markedly increasing SOD and GPx activity	Anthocyanins reduced body weight could also reduce the size of adipocytes, leptin secretion, serum glucose, triglycerides, total cholesterol, LDL-cholesterol, and liver triglycerides	[191]
Phenolic acid	Curcumin	Mice	A direct effect of bioactive metabolites reaching the adipose tissue rather than from changes in GM composition	Nutritional doses of Curcuma longa is able to decrease proinflammatory cytokine expression in subcutaneous adipose tissue	An effect independent of adiposity, immune-cell recruitment, angiogenesis, or modulation of GM controlling inflammation	[192]
	Curcumin	LDLR−/− mice	Curcumin improves intestinal barrier function and prevents the development of metabolic diseases	Significantly attenuated the Western diet-induced increase in plasma LPS levels	Significantly reduced WD-induced glucose intolerance and atherosclerosis	[193]
	Curcumin	Human IEC lines Caco-2 and HT-29	Curcumin modulates chronic inflammatory diseases by reducing intestinal barrier dysfunction despite poor bioavailability	Curcumin significantly attenuated LPS-induced secretion of master cytokine IL-1β from IEC and macrophages. Also reduced IL-1β-induced activation of p38 MAPK in IEC and subsequent increase in expression of myosin light-chain kinase	Curcumin attenuates WD-induced development of type 2 diabetes mellitus and atherosclerosis	[194]
Stilbenes	Resveratrol	Kunming mice	HF microbiomes were clearly different from those in CT and HF-RES mice. After treatment, Lactobacillus and Bifidobacterium were significantly increased, whereas Enterococcus faecalis was significantly decreased, resulting in a higher abundance of Bacteroidetes and a lower abundance of Firmicutes		Treatment inhibited increases in body and fat weight in HF mice. Decreased blood glucose to control levels, decreased blood insulin and serum total cholesterol compared with HF mice. Severe steatosis seen in HF mice was well prevented in treated mice. Treatment significantly suppressed expression of PPAR-γ, Acc1, and Fas, suggesting inhibition of triglyceride storage in adipocytes	[195]
	Resveratrol	Glp1r−/− mice	Treatment modified GM	Decreased the inflammatory status of mice	Glucoregulatory action of RSV in HFD-fed diabetic wild-type mice, in part through modulation of the enteroendocrine axis in vivo	[196]
	Resveratrol	Wistar rats	Trans-resveratrol supplementation alone or in combination with quercetin scarcely modified the GM profile but acted at the intestinal level, altering mRNA expression of tight-junction proteins and inflammation-associated genes	Altering mRNA expression of tight-junction proteins and inflammation-associated genes	Administration of resveratrol and quercetin together prevented body weight gain and reduced serum insulin levels. Effectively reduced serum insulin levels and insulin resistance	[188]
	Resveratrol	Adipocytes		Generally, resveratrol opposed the effect induced by LPS, functioning as an ameliorating factor in disease state	LPS altering glycosylation processes of the cell. Resveratrol ameliorates dysfunctioning adipose tissue induced by inflammatory stimulation	[197]
	Resveratrol	Humans	Steroid metabolism of the affected GM should be studied in detail		Subtle but robust effects on several metabolic pathways	[198]
	Piceatannol	C57BL/6 mice	Pic altered the composition of the GM by increasing Firmicutes and Lactobacillus and decreasing Bacteroidetes		Pic significantly reduced mouse body weight in a dose-dependent manner. Significantly decreased the weight of liver, spleen, perigonadal, and retroperitoneal fat compared with the HFD group. Pic significantly reduced adipocyte cell size of perigonadal fat and decreased weight of liver	[199]
	Piceatannol	Zucker obese rats	It did not modify the profusion of the most abundant phyla in GM, though slight changes were observed in the abundance of several Lactobacillus, Clostridium, and Bacteroides species belonging to Firmicutes and Bacteroidetes	Shows a tendency to reduce plasma LPS by 30%	Pic did not reduce either hyperphagia or fat accumulation. There is a tendency toward the decrease of circulating on-esterified fatty acids, LDL-cholesterol, and lactate. While Pic tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy	[155]
Organosulfur compounds	GEO (garlic essential oil); DADS (DiAllyl DiSulfide)	C57BL/6 mice		Significantly decreased the release of proinflammatory cytokines in liver, accompanied by elevated antioxidant capacity via inhibition of cytochrome P450 2E1 expression	GEO and DADS dose-dependently exerted antiobesity and antihyperlipidemic effects by reducing HFD-induced body weight gain, adipose tissue weight, and serum biochemical parameters	[200]