Effects of fermented sweet potato residue on nutrient digestibility, meat quality, and intestinal microbes in broilers.

This study aimed to investigate the effects of different proportions of dietary fermented sweet potato residue (FSPR) supplementation as a substitute for corn on the nutrient digestibility, meat quality, and intestinal microbes of yellow-feathered broilers. Experiment 1 (force-feeding) evaluated the nutrient composition and digestibility of mixtures with different proportions of sweet potato residue (70%, 80%, 90%, and 100%) before and after fermentation. In Experiment 2 (metabolic growth), a total of 420 one-day-old yellow-feathered broilers were randomly allocated to 4 groups and fed corn-soybean meal-based diets with 0, 5%, 8%, and 10% FSPR as a substitute for corn. The force-feeding and metabolic growth experiments were performed for 9 and 70 d, respectively. The treatment of 70% sweet potato residue (after fermentation) had the highest levels of crude protein, ether extract, and crude fiber and improved the digestibility of crude protein and amino acids (P < 0.05). Although dietary FSPR supplementation at different levels had no significant effect on growth performance and intestinal morphology, it improved slaughter rate, half-chamber rate, full clearance rate, and meat color, as well as reduced cooking loss in the breast and thigh muscles (P < 0.05). Dietary supplementation with 8% and 10% FSPR increased the serum immunoglobulin M and immunoglobulin G levels in broilers (P < 0.05). Furthermore, 10% FSPR increased the Shannon index and Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-010 and Romboutsia abundances and decreased Sutterella and Megamonas abundances (P < 0.05). Spearman's correlation analysis showed that meat color was positively correlated with Ruminococcaceae_UCG-014 (P < 0.05) and negatively correlated with Megamonas (P < 0.05). Collectively, 70% sweet potato residue (after fermentation) had the best nutritional value and nutrient digestibility. Dietary supplementation with 8% to 10% FSPR as a substitute for corn can improve the slaughter performance, meat quality, and intestinal microbe profiles of broilers. Our findings suggest that FSPR has the potential to be used as a substitute for corn-soybean meals to improve the meat quality and intestinal health of broilers.

Zinc lactate alleviates oxidative stress by modulating crosstalk between constitutive androstane receptor signaling pathway and gut microbiota profile in weaned piglets.

This study aimed to determine the regulatory mechanism of dietary zinc lactate (ZL) supplementation on intestinal oxidative stress damage in a paraquat (PQ)-induced piglet model. Twenty-eight piglets (mean body weight 9.51 ± 0.23 kg) weaned at 28 d of age were randomly divided into control, ZL, PQ, and ZL + PQ groups (n = 7 in each group). The ZL-supplemented diet had little effect on growth performance under normal physiological conditions. However, under PQ challenge, ZL supplementation significantly improved average daily gain (P < 0.05) and reduced the frequency of diarrhea. ZL improved intestinal morphology and ultrastructure by significantly increasing the expression level of the jejunal tight junction protein, zonula occludens-1 (ZO-1) (P < 0.05), and intestinal zinc transport and absorption in PQ-induced piglets, which reduced intestinal permeability. ZL supplementation also enhanced the expression of antioxidant and anti-inflammatory factor-related genes and decreased inflammatory cytokine expression and secretion in PQ-induced piglets. Furthermore, ZL treatment significantly inhibited the activation of constitutive androstane receptor (CAR) signaling (P < 0.01) in PQ-induced piglets and altered the structure of the gut microbiota, especially by significantly increasing the abundance of beneficial gut microbes, including UCG_002, Ruminococcus, Rikenellaceae_RC9_gut_group, Christensenellaceae_R_7_group, Treponema, unclassified_Christensenellaceae, and unclassified_Erysipelotrichaceae (P < 0.05). These data reveal that pre-administration of ZL to piglets can suppress intestinal oxidative stress by improving antioxidant and anti-inflammatory capacity and regulating the crosstalk between CAR signaling and gut microbiota.

d-Aspartate in Low-Protein Diets Improves the Pork Quality by Regulating Energy and Lipid Metabolism via the Gut Microbes.

d-Aspartate is critical in maintaining hormone secretion and reproductive development in mammals. This study investigated the mechanism of different d-aspartate levels (0, 0.005, 0.05, and 0.5% d-aspartate) in low-protein diets on growth performance and meat quality by mediating the gut microbiota alteration in pigs. We found that adding 0.005% d-aspartate to a low-protein diet could dramatically improve the growth performance during the weaned and growing periods. Dietary d-aspartate with different levels markedly increased the back fat, and 0.5% d-aspartate significantly increased the redness in 24 h and reduced the shear force of the longissimus dorsi (LD) muscle. Moreover, d-aspartate treatments decreased the mRNA expression of MyHC II a and MyHC IIx in the LD muscle. The protein expression of MyH1, MyH7, TFAM, FOXO1, CAR, UCP2, and p-AMPK was upregulated by 0.005% d-aspartate. Additionally, the abundance of Alistipes, Akkermansia, and the [Eubacterium]_coprostanoligenes_group in the intestinal chyme of pigs was significantly decreased by d-aspartate treatments at the genus level, which was also accompanied by a significant decrease in acetate content. These differential microorganisms were significantly correlated with meat quality characteristics. These results indicated that d-aspartate in low-protein diets could improve the growth performance and meat quality in pigs by regulating energy and lipid metabolism via the alteration of gut microbiota.

Crosstalk between trace elements and T-cell immunity during early-life health in pigs.

With gradual ban on the use of antibiotics, the deficiency and excessive use of trace elements in intestinal health is gaining attention. In mammals, trace elements are essential for the development of the immune system, specifically T-cell proliferation, and differentiation. However, there remain significant gaps in our understanding of the effects of certain trace elements on T-cell immune phenotypes and functions in pigs. In this review, we summarize the specificity, development, subpopulations, and responses to pathogens of porcine T cells and the effects of functional trace elements (e.g., iron, copper, zinc, and selenium) on intestinal T-cell immunity during early-life health in pigs. Furthermore, we discuss the current trends of research on the crosstalk mechanisms between trace elements and T-cell immunity. The present review expands our knowledge of the association between trace elements and T-cell immunity and provides an opportunity to utilize the metabolism of trace elements as a target to treat various diseases.

CRISPR-activation screen identified potassium channels for protection against mycotoxins through cell cycle progression and mitochondrial function.

Zearalenone (ZEA) exposure has carcinogenic effects on human and animal health by exhibiting intestinal, hepatic, and renal toxicity. At present, the underlying mechanisms on how ZEA induces apoptosis and damage to tissues still remain unclear. In this study, we aimed to identify genes that modulate the cellular response to ZEA using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screening, and further validate novel gene functions to elucidate molecular mechanisms underlying particular biological processes in vivo and in vitro. Two ZEA-resistant cell lines, designated Ov-KCNJ4 and Ov-KCNJ12, were yielded by CRISPR activation screening which had significant changes in ZEA resistance and growth rates. Results showed that ZEA could interact with the cell membrane proteins KCNJ4 and KCNJ12, inducing cell cycle arrest, disruption of DNA replication and base excision repair. Overexpression of KCNJ4 and KCNJ12 was involved in ZEA resistance by regulating cell cycle to neutralize toxicity, sustaining mitochondrial morphology and function via attenuating the damage from oxidative stress in the KCNJ4-mitoKATP pathway. In vivo experiments showed that AAV-KCNJ4 delivery significantly improved ZEA-induced renal impairment and increased antioxidative enzyme activity by improving mitochondrial function. Our findings suggest that increasing potassium channel levels may be a putative therapeutic target for mycotoxin-induced damage.

Serine signaling governs metabolic homeostasis and health.

Serine has functions that are involved in metabolic homeostasis and health in pathological or stressful situations. Notably, the de novo serine synthesis pathway (SSP) plays a vital role in targeted regulation of immune responses, cell proliferation, and lipid/protein metabolism. The presentation of serine residues derived from SSP may be a signal of stress and provide novel insights into the relationship between metabolic homeostasis and diseases. Here, we summarize the current trends in understanding the regulatory mechanisms of serine metabolism, discuss how serine signaling governs metabolic and antistress processes, including oxidative stress, immunity, energy and lipid metabolism, intestinal microbiota, and the neurological system. We present a possible framework by which serine metabolism maintains metabolic homeostasis and treats human diseases.

Serine Administration Improves Selenium Status, Oxidative Stress, and Mitochondrial Function in Longissimus Dorsi Muscle of Piglets with Intrauterine Growth Retardation.

Intrauterine growth retardation (IUGR) causes oxidative stress in the skeletal muscle. Serine and selenoproteins are involved in anti-oxidative processes; however, whether IUGR affects selenium status and whether serine has beneficial effects remain elusive. Here, we investigated the effects of serine administration on selenium nutritional status and oxidative stress in the longissimus dorsi muscle of piglets with IUGR. Six newborn Min piglets having normal birth weight were administered saline, and 12 IUGR piglets were either administered saline or 0.8% serine. The results showed a lower selenium content in skeletal muscle in IUGR piglets, which was restored after serine administration. IUGR piglets showed a disturbed expression of genes encoding selenoproteins, with decreased expression of GPX2, GPX4, TXNRD1, and TXNRD3 and increased expression of DIO1, DIO2, SELF, SELM, SELP, and SELW. Notably, serine administration restored the expression levels of these genes. In accordance with the changes in gene expression, the activity of GPX, TXNRD, and DIO and the content of GSH and SELP were also altered, whereas serine administration restored their contents and activities. Moreover, we observed severe oxidative stress in the skeletal muscle of IUGR piglets, as indicated by decreased GSH content and increased MDA and PC content, whereas serine administration alleviated these changes. In conclusion, our results indicate that IUGR piglets showed a disturbed expression of genes encoding selenoproteins, accompanied by severe oxidative stress. Serine administration can improve selenium status, oxidative stress, and mitochondrial function in the longissimus dorsi muscle of piglets with IUGR. These results suggest that serine could potentially be used in the treatment of IUGR in piglets.

Improvement of Ulcerative Colitis by Aspartate via RIPK Pathway Modulation and Gut Microbiota Composition in Mice.

The intestine requires a great deal of energy to maintain its health and function; thus, energy deficits in the intestinal mucosa may lead to intestinal damage. Aspartate (Asp) is an essential energy source in the intestinal mucosa and plays a vital part in gut health. In the current study, we hypothesized that dietary supplementation of Asp could alleviate DSS-induced colitis via improvement in the colonic morphology, oxidative stress, cell apoptosis, and microbiota composition in a mouse model of dextran. Asp administration decreased the disease activity index, apoptosis, myeloperoxidase, eosinophil peroxidase, and proinflammatory cytokine (IL-1ß and TNF-α) concentrations in the colonic tissue, but improved the body weight, average daily food intake, colonic morphology, and antioxidant-related gene (GPX1 and GPX4) expression in DSS-treated mice. Expression levels of RIPK1 and RIPK3 were increased in the colon following Asp administration in the DSS-induced mice, whereas the MLKL protein expression was decreased. 16S rRNA sequencing showed that Asp treatment increased the abundance of Lactobacillus and Alistipes at the gene level, and Bacteroidetes at the phylum level, but decreased the abundance of Actinobacteria and Verrucomicrobia at the phylum level. Asp may positively regulate the recovery of DSS-induced damage by improving the immunity and antioxidative capacity, regulating RIPK signaling and modulating the gut microbiota composition.

Ferroptosis and Its Multifaceted Role in Cancer: Mechanisms and Therapeutic Approach.

Ferroptosis, a new type of non-apoptotic cell death modality, is different from other modes of cell death and has been primarily found in tumor cells. Previous studies have reported that ferroptosis can be triggered by specific modulators (e.g., drugs, nutrients, and iron chelators), leading to increased intracellular lipid reactive oxygen species (ROS) accumulation and iron overload. Recent reports have shown that ferroptosis at the cellular and organism levels can prevent an inflammatory storm and cancer development. Emerging evidence suggests potential mechanisms (e.g., system Xc-, glutathione peroxidase 4 (GPX4), lipid peroxidation, glutathione (GSH), and iron chelators) are involved in ferroptosis, which may mediate biological processes such as oxidative stress and iron overload to treat cancer. To date, there are at least three pathways that mediate ferroptosis in cancer cells: system Xc-/GSH/GPX4, FSP1/CoQ10/NAD(P)H, and ATG5/ATG7/NCOA4. Here, we summarize recent advances in the occurrence and development of ferroptosis in the context of cancer, the associations between ferroptosis and various modulators, and the potential mechanisms and therapeutic strategies targeting ferroptosis for the treatment of cancer.

Glutamine in suppression of lipopolysaccharide-induced piglet intestinal inflammation: The crosstalk between AMPK activation and mitochondrial function.

The study was conducted to investigate the regulatory mechanism of glutamine (Gln) on intestinal inflammation in an Escherichia coli lipopolysaccharide (E. coli LPS)-induced in vivo and in vitro models. Piglets (n = 8) weaned at 21 d of age were fed a basal diet (control and LPS groups) or 1% Gln diet (Gln + LPS group) ad libitum for 4 weeks. On d 22, 24, 26 and 28, piglets in the LPS and Gln + LPS groups were intraperitoneally injected with E. coli LPS. Intestinal porcine epithelial cells (IPEC-J2) (n = 6) induced by LPS were used to assess related mechanisms and compound C was used to inhibit adenosine 5'-monophosphate-activated protein kinase (AMPK) activity. Our current results showed that compared with the LPS treatment, the Gln + LPS treatment had better growth performance and greater villus height (P < 0.05), and the Gln + LPS treatment reduced the rate of diarrhea by 6.4% (P < 0.05); the Gln + LPS treatment decreased serum tumor necrosis factor (TNF-ɑ), interleukin-6 (IL-6), K+, cortisol and insulin levels, whereas increased (P < 0.05) serum immunoglobulin M and epidermal growth factor levels; the Gln + LPS treatment increased (P < 0.05) the expression of aquaporins and AMPK pathway-associated targets in the jejunum and ileum of piglets, whereas decreased the expression of ion transporters (P < 0.05). The in vitro results showed that 4 mmol/L Gln administration could inhibit (P < 0.05) cell apoptosis and interleukin-1ß (IL-1ß), IL-6 and TNF-ɑ secretion in LPS-induced IPEC-J2 cells, promote (P < 0.05) mitochondrial respiratory metabolism and increase (P < 0.05) the number of mitochondria and mitochondrial membrane potential. The activity of AMPK was elevated by 70% to 300% in Gln-treated IPEC-J2 cells under LPS challenge or normal conditions. Our results indicate that pre-administration of Gln to piglets suppresses intestinal inflammation by modulating the crosstalk between AMPK activation and mitochondrial function.

Intestinal accumulation of microbiota-produced succinate caused by loss of microRNAs leads to diarrhea in weanling piglets.

Diarrheal disease is a common health problem with complex causality. Although diarrhea is accompanied by disturbances in microbial diversity, how gut microbes are involved in the occurrence of diarrhea remains largely unknown. Here, using a pig model of post-weaning stress-induced diarrhea, we aim to elucidate and enrich the mechanistic basis of diarrhea. We found significant alterations in fecal microbiome, their metabolites, and microRNAs levels in piglets with diarrhea. Specifically, loss of ssc-miRNA-425-5p and ssc-miRNA-423-3p, which inhibit the gene expression of fumarate reductase (frd) in Prevotella genus, caused succinate accumulation in piglets, which resulted in diarrhea. Single-cell RNA sequencing indicated impaired epithelial function and increased immune response in the colon of piglet with diarrhea. Notably, the accumulated succinate increased colonic fluid secretion by regulating transepithelial Cl-secretion in the epithelial cells. Meanwhile, succinate promoted colonic inflammatory responses by activating MyD88-dependent TLR4 signaling in the macrophages. Overall, our findings expand the mechanistic basis of diarrhea and suggest that colonic accumulation of microbiota-produced succinate caused by loss of miRNAs leads to diarrhea in weanling piglets.

Effects of Lysine-Lysine Dipeptide on Serum Amino Acid Profiles, Intestinal Morphology, and Microbiome in Suckling Piglets.

Aims: Small peptides are more energy-saving and efficiently absorbed compared to amino acids. Our study aimed to evaluate the effect of the Lys-Lys dipeptide on the improvement of growth performance, amino acid metabolism, and gut development in suckling piglets. Methods and Results: Twenty-eight newborn suckling piglets were orally administrated with 0.1%, 1%, and 5% Lys-Lys dipeptide for 21 days. Our results showed that the Lys-Lys dipeptide has no significant effect on growth performance and intestinal morphology compared with the control group. We also found that the 1% Lys-Lys dipeptide significantly increased the concentrations of serum Lys, Thr, Phe, and Pro while decreasing Cys compared to the control group. Similarly, the 5% Lys-Lys dipeptide markedly increased the concentrations of serum Lys, Iso, Thr, Asp, Glu, and Pro compared to the control group. Moreover, the Lys-Lys dipeptide downregulated the expression of jejunal Slc7a1, Slc7a2, and Slc15a1 and ileal Slc7a2. Additionally, the Lys-Lys dipeptide decreased the microbiota richness indices and relative abundance of Bacteroidales. Conclusion: In this study, we found that the Lys-Lys dipeptide contributes to the metabolism of amino acids but failed to affect the growth performance of piglets. Additionally, the Lys-Lys dipeptide decreased the relative abundance of Bacteroidales. These results provide a theoretical for the future application and research of Lys-Lys dipeptide in intestinal development of suckling piglets.

Serine Supplementation in the Diets of Late Gestating and Lactating Sows Improves Selenium Nutritional Status in Sows and Their Offspring.

Serine can regulate selenoprotein expression, and dietary serine is correlated with the contents of plasma selenoprotein P (Sepp1) and milk selenium (Se) in lactating mothers. Based on this, we investigated the effects of serine supplementation in the diets of late gestating and lactating sows on Sepp1 and Se contents in sows and their offspring. A total of 72 sows were assigned to four groups. During the experiment, sows were fed either a basal diet or basal diets supplemented with three different levels of serine. The results showed that maternal dietary serine had no effect on the Se content in the serum of sows and their offspring, whereas it significantly increased the Se content in the liver of piglets at the age of 21 days. Maternal dietary serine significantly increased Sepp1 content, either in the serum of sows or that in their offspring at the ages of 3 days, 7 days, and 21 days. Additionally, maternal dietary serine significantly increased litter weight and the average body weight of piglets at the age of 11 days. Notably, a positive correlation was found between the average body weight of piglets at the age of 11 days and serum Sepp1 content in piglets, at the age of either 3 days or 7 days. In conclusion, maternal dietary serine supplementation could improve Se nutritional status in sows and their offspring. These beneficial changes may contribute to the higher body weight of the offspring.

Fecal miR-142a-3p from dextran sulfate sodium-challenge recovered mice prevents colitis by promoting the growth of Lactobacillus reuteri.

Feces are enriched with microRNAs (miRNAs) that shape the gut microbiota. These miRNAs are differentially expressed in the feces of healthy and diseased subjects. However, whether fecal miRNAs in subjects with inflammatory bowel diseases are involved in regulating microbiota composition and whether they have any beneficial effects remains unknown. Here, we studied the fecal microbiome composition and miRNA abundance in mice with dextran sulfate sodium (DSS)-induced colitis and mice at the recovery phase to explore different miRNAs expressed, their relations with microbial abundance, and their effects on colitis. We found that miR-142a-3p expression was significantly increased in the feces of mice recovered from colitis and that it could alleviate disease symptoms in mice treated with DSS in a microbiome-dependent manner. Specifically, miR-142a-3p promoted the growth of Lactobacillus reuteri, which had a high abundance in the feces of mice recovered from colitis, by regulating transcripts of polA and locus tag LREU_RS03575. Moreover, L. reuteri, as well as its metabolite reuterin, could alleviate DSS-induced disease symptoms. These results highlight the role of fecal miR-142a-3p in the prevention of colitis. We propose that the feces of subjects who have recovered from diseases might be enriched with miRNAs with preventive effects against those diseases.

Glutathione Protects against Paraquat-Induced Oxidative Stress by Regulating Intestinal Barrier, Antioxidant Capacity, and CAR Signaling Pathway in Weaned Piglets.

Endogenous glutathione (GSH) effectively regulates redox homeostasis in the body. This study aimed to investigate the regulatory mechanism of different dietary levels of GSH supplementation on the intestinal barrier and antioxidant function in a paraquat-induced stress-weaned piglet model. Our results showed that dietary 0.06% GSH supplementation improved the growth performance of weaned piglets under normal and stressful conditions to some degree and decreased the diarrhea rate throughout. Exogenous GSH improved paraquat-induced changes in intestinal morphology, organelle, and permeability and reduced intestinal epithelial cell apoptosis. Moreover, GSH treatment alleviated intestinal oxidative stress damage by upregulating antioxidant (GPX4, CnZnSOD, GCLC, and GCLM) and anti-inflammatory (IL-10) gene expression and downregulating inflammatory cytokines (IFN-γ and IL-12) gene expression. Furthermore, GSH significantly reduced the expression levels of constitutive androstane receptor (CAR), RXRα, HSP90, PP2Ac, CYP2B22, and CYP3A29, and increased the expression levels of GSTA1 and GSTA2 in the jejunum and ileum of paraquat-induced piglets. We conclude that exogenous GSH protects against oxidative stress damage by regulating the intestinal barrier, antioxidant capacity, and CAR signaling pathway.

Aspartate Metabolism Facilitates IL-1ß Production in Inflammatory Macrophages.

Increasing evidence support that cellular amino acid metabolism shapes the fate of immune cells; however, whether aspartate metabolism dictates macrophage function is still enigmatic. Here, we found that the metabolites in aspartate metabolism are depleted in lipopolysaccharide (LPS) plus interferon gamma (IFN-γ)-stimulated macrophages. Aspartate promotes interleukin-1ß (IL-1ß) secretion in M1 macrophages. Mechanistically, aspartate boosts the activation of hypoxia-inducible factor-1α (HIF-1α) and inflammasome and increases the levels of metabolites in aspartate metabolism, such as asparagine. Interestingly, asparagine also accelerates the activation of cellular signaling pathways and promotes the production of inflammatory cytokines from macrophages. Moreover, aspartate supplementation augments the macrophage-mediated inflammatory responses in mice and piglets. These results uncover a previously uncharacterized role for aspartate metabolism in directing M1 macrophage polarization.

Exogenous and Endogenous Serine Deficiency Exacerbates Hepatic Lipid Accumulation.

Serine is involved in the regulation of hepatic lipid metabolism. However, whether exogenous or endogenous serine deficiency affects lipid accumulation in the liver and related mechanisms is unclear. Here, we investigated the effects of serine deficiency on hepatic fat accumulation in mice fed a serine-deficient diet or in mice supplemented with the D-3-phosphoglycerate dehydrogenase (PHGDH) inhibitor NCT-503. Both treatments produced an increase in body weight and liver weight and higher triglyceride content in the liver. Both treatments also exacerbated hepatic inflammatory responses and oxidative stress. Importantly, NCT-503 supplementation significantly inhibited PHGDH activity and decreased the serine content in the liver. Dietary serine deficiency significantly affected the colonic microbiota, characterized by a decreased ratio of Firmicutes/Bacteroidetes and decreased proportion of Bifidobacterium. Dietary serine deficiency additionally resulted in significantly decreased colonic and serum acetate and butyrate levels. The collective results indicate that NCT-503 supplementation may contribute to overaccumulation of hepatic lipid, by causing hepatic serine deficiency, while dietary serine deficiency may produce similar outcomes by affecting the gut-microbiota-liver axis.

D-Galactose Induces Chronic Oxidative Stress and Alters Gut Microbiota in Weaned Piglets.

Oxidative stress commonly occurs in pig production, which can severely damage the intestinal function of weaned piglets. This study was conducted to investigate the effects of D-galactose with different levels used to induce chronic oxidative stress on growth performance, intestinal morphology and gut microbiota in weaned piglets. The results showed that addition of 10 and 20 g/kg BW D-galactose reduced average daily gain and average daily feed intake from the first to the third week. 10 g/kg BW D-galactose increased the concentration of serum MDA at the second and third week. 10 g/kg BW D-galactose significantly influenced the jejunal and ileal expressions of GPx1, CAT1, and MnSOD. The results of 16S rRNA sequencing showed that compared with the control, 10 and 20 g/kg BW D-galactose significantly decreased the relative abundance of Tenericutes, Erysipelotrichia, Erysipelotrichales, and Erysipelotrichaceae, while increased the relative abundance of Negativicutes, Selenomonnadales, and Veillonellaceae. The results indicated that treatment with 10 g/kg BW/day D-galactose for 3 weeks could induce chronic oxidative stress, reduce the growth performance and alter gut microbiota in weaned piglets.

Natural Polyphenols as Targeted Modulators in Colon Cancer: Molecular Mechanisms and Applications.

Colon cancer commonly develops from long-term chronic inflammation in the intestine and seriously threatens human health. Natural polyphenols have been valued as a crucial regulator of nutrient metabolism and metabolic diseases, owing to their anti-inflammatory and antioxidant functions and the ability to maintain a balance between gut microbes and their hosts. Notably, experimental and clinical evidence has shown that natural polyphenols could act as a targeted modulator to play a key role in the prevention or treatment of colon cancer. Thus, in this review, we summarized recent advances in the possible regulatory mechanism and the potential application of natural polyphenols in colon cancer, which might be regarded as a novel platform for the colon cancer management.