Exposure to flutolanil at environmentally relevant concentrations can induce image and non-image-forming failure of zebrafish larvae through neuro and visual disruptions.

Numerous pesticides pose a threat to aquatic ecosystems, jeopardizing aquatic animal species and impacting human health. While the contamination of aquatic environment by flutolanil and its adverse effects on animal in the treatment of rich sheath blight have been reported, the neuro-visual effects of flutolanil at environmentally relevant concentrations remain unknown. In this study, we administered flutolanil to zebrafish embryos (0, 0.125, 0.50 and 2.0 mg/L) for 4 days to investigate its impact on the neuro and visual system. The results revealed that flutolanil induced abnormal behavior in larvae, affecting locomotor activity, stimuli response and phototactic response. Additionally, it led to defective brain and ocular development and differentiation. The disruption extended to the neurological system and visual phototransduction of larvae, evidenced by significant disturbances in genes and proteins related to neurodevelopment, neurotransmission, eye development, and visual function. Untargeted metabolomics analysis revealed that the GABAergic signaling pathway and increased levels of glutamine, glutamate, andγ-aminobutyric acid were implicated in the response to neuro and visual system injury induced by flutolanil, contributing to aberrant development, behavioral issues, and endocrine disruption. This study highlights the neuro-visual injury caused by flutolanil in aquatic environment, offering fresh insights into the mechanisms underlying image and non-image effects.

Bee colonies map the short- and medium-chain chlorinated paraffin contamination from the apiary environment.

Chlorinated paraffins (CPs) are industrial chemicals that have potential adverse effects in the environment and on human health. This study investigated CPs in apiary environment, honeybees, and bee products from two rural areas of Beijing, China. The median concentrations of short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) were 22 and 1.6 ng/m3 in the ambient air, 1350 and 708 ng/g dry mass (dw) in bees, 1050 and 427 ng/g dw in flowers, 37 and 54 ng/g in honey, 78 and 53 ng/g dw in bee pollen, 36 and 30 ng/g dw in soil, and 293 and 319 ng/g dw in bee wax. C10Cl6-7 and C14Cl7-8 dominated SCCPs and MCCPs in these samples, respectively. The concentrations and distributions of CPs in samples from apiaries located in the two regions varied. Long-range transportation of air masses was identified as an important source of CPs in apiaries. A close relationship between CPs in bees and the apiary environment indicated that bees could act as bioindicators for CP contamination in the environment. A human health risk assessment found that there were low risks for adults and children exposed to CPs through consumption of honey and pollen from the studied regions.

Antioxidant Polyphenols from Lespedeza bicolor Turcz. Honey: Anti-Inflammatory Effects on Lipopolysaccharide-Treated RAW 264.7 Macrophages.

Although the honey produced by Lespedeza bicolor Turcz. is precious because of its medicinal value, its pharmacological mechanism is still unclear. Here, its anti-inflammatory and antioxidant functions on lipopolysaccharide (LPS)-treated murine RAW 264.7 macrophages were analyzed using targeted and non-targeted metabolomics. Results showed that twelve polyphenols were identified in L. bicolor honey using UHPLC-QQQ-MS/MS. L. bicolor honey extract could scavenge the free radicals DPPH• and ABTS+ and reduce Fe3+. Furthermore, pretreatment with L. bicolor honey extract significantly decreased NO production; suppressed the expression of COX-2, IL-10, TNF-α, and iNOS; and upregulated HO-1's expression in the cells with LPS application. UHPLC-Q-TOF-MS/MS-based metabolomics results revealed that L. bicolor honey extract could protect against inflammatory damage caused by LPS through the reduced activation of sphingolipid metabolism and necroptosis pathways. These findings demonstrate that L. bicolor honey possesses excellent antioxidant and anti-inflammatory activities.

Stress Response in the Honeybee (Apis mellifera L.) Gut Induced by Chlorinated Paraffins at Residue Levels Found in Bee Products.

Chlorinated paraffins (CPs) have become global pollutants and are of considerable concern as a result of their persistence and long-distance transmission in the environment and toxicity to mammals. However, their risks to pollinating insects are unknown. Honeybees are classical pollinators and sensitive indicators of environmental pollution. Herein, the effects of CPs on the gut microenvironment and underlying mechanisms were evaluated and explored using Apis mellifera L. Both short- and medium-chain CPs had significant sublethal effects on honeybees at a residue dose of 10 mg/L detected in bee products but did not significantly alter the composition or diversity of the gut microbiota. However, this concentration did induce significant immune, detoxification, and antioxidation responses and metabolic imbalances in the midgut. The mechanisms of CP toxicity in bees are complicated by the complex composition of these chemicals, but this study indicated that CPs could substantially affect intestinal physiology and metabolic homeostasis. Therefore, CPs in the environment could have long-lasting impacts on bee health. Future studies are encouraged to identify novel bioindicators of CP exposure to detect early contamination and uncover the detailed mechanisms underlying the adverse effects of CPs on living organisms, especially pollinating insects.

Integrated microbiomic and metabolomic analyses reveal the mechanisms by which bee pollen and royal jelly lipid extracts ameliorate colitis in mice.

Bee pollen (BP) and royal jelly (RJ) have shown therapeutic effects against colitis, but the functional components contained therein remain elusive. Here, we used an integrated microbiomic-metabolomic strategy to clarify the mechanism by which bee pollen lipid extracts (BPL) and royal jelly lipid extracts (RJL) ameliorated dextran sulfate sodium (DSS)-induced colitis in mice. Lipidomic results showed that levels of ceramide (Cer), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) were significantly higher in BPL than in RJL. The anti-inflammatory efficacy of BPL surpassed that of RJL, although both BPL and RJL could attenuate DSS-induced colitis through several mechanisms: reducing the disease activity index (DAI); decreasing histopathological damage; inhibiting the expression of genes encoding proinflammatory cytokines; improving intestinal microbial community structure, and modulating host metabolism. These findings demonstrated that BPL and RJL have great potential as functional ingredients for the production of dietary supplements to prevent early colitis.

Exploring RNA methylation as a promising biomarker for assessing sublethal effects of fipronil on honeybees (Apis mellifera L.).

Honeybees play a crucial role as pollinators for crops and are regarded as sensitive bioindicators of environmental health. The widespread use of pesticides poses a severe threat to honeybee survival. However, there is limited information available on the specific risks associated with fipronil exposure in honeybees, particularly concerning the impact on RNA methylation throughout their lifespan. This study aimed to evaluate the effects of sublethal concentrations of fipronil on RNA m6A and m5C methylations, along with the associated genes in honeybee larvae and newly emerged adults. LC-MS/MS analysis revealed a notable hypomethylation of m5C in larvae, while hypermethylation of m6A was observed in the adult brain. Significant changes in the expression of genes such as AmWTAP, AmYTHDF, AmALKBH4, AmALKBH6, AmALKBH8, AmNSUN5, AmNOP2, AmTET1, and AmYBX1 were observed in the adult brain, whereas alterations in the expression of AmNSUN2, AmMETTL14, AmALKBH1, AmALKBH4, AmALKBH6 AmALYREF, AmTET1, and AmYBX1 were observed in the larvae. Notably, the expression of AmALKBH1 was not detected in any fipronil-treated larvae, suggesting its potential as an early risk indicator for honeybee larvae in future assessments. This pioneering study provides insights into the effects of fipronil on RNA methylations in honeybees and explores the possibility of employing RNA methylation as a tool for assessing pesticide risks in this important pollinator species. These findings offer new perspectives on honeybee protection and the development of toxicity evaluation systems for pesticides.

Chronic Exposure to Polystyrene Microplastic Fragments Has No Effect on Honey Bee Survival, but Reduces Feeding Rate and Body Weight.

Microplastics (MPs), in the form of fragments and fibers, were recently found in honey samples collected in Ecuador as well as in honey bees collected from Denmark and China. However, little is known about how MPs impact bee health. To fill this knowledge gap, we investigated the potential toxicity of irregularly shaped polystyrene (PS)-MP fragments on honey bee health. In the first experiment of its kind with honey bees, we chronically exposed bees with a well-established gut microbiome to small (27 ± 17 µm) or large (93 ± 25 µm) PS-MP fragments at varying concentrations (1, 10, 100 µg mL-1) for 14 days. Bee mortality, food consumption, and body weight were all studied. We found that chronic exposure to PS-MP fragments has no effect on honey bee survival, but reduced the feeding rate and body weight, particularly at 10 µg PS-MP fragments per mL, which may have long-term consequences for honey bee health. The findings of this study could assist in the risk assessment of MPs on pollinator health.

Identification of characteristic markers for monofloral honey of Astragalus membranaceus var. mongholicus Hsiao: A combined untargeted and targeted MS-based study.

Astragalus membranaceus var. mongholicus Hsiao (Am) is a widely used traditional Chinese herbal medicine. The monofloral honey from Am plant nectar collected by honeybees (MH-Am) has potential medicinal activities. Quality control of MH-Am requires discovery of characteristic markers. In this study, calycosin and formononetin were identified as reliable chemical markers for MH-Am authentication, which were shared with its plant (P-Am), but absent in other honeys based on untargeted mass spectrometry (MS) analysis. The contents of calycosin and formononetin in MH-Am, other honeys and P-Am were determined through a targeted MS-based quantitative approach. Furthermore, free radical scavenging assays showed that calycosin functioned directly in the antioxidative activity of MH-Am. Thus, calycosin has great potential to be certified as a bioactive marker contributing to future quality control of commercial MH-Am products.

Disinfectant dodecyl dimethyl benzyl ammonium chloride (DDBAC) disrupts gut microbiota, phospholipids, and calcium signaling in honeybees (Apis mellifera) at an environmentally relevant level.

One of the impacts of the Coronavirus disease 2019 (COVID-19) pandemic has been a profound increase in the application amounts of disinfectants. Dodecyl dimethyl benzyl ammonium chloride (DDBAC) is a widely used disinfectant, yet its hazards to non-target species remain largely unknown. We are unaware of any studies assessing DDBAC's impacts on honeybee, a pollinator species that is a useful indicator of environmental pollution essential for many forms of agricultural production. Here, we assessed the potentially negative effects of DDBAC on honeybees. After conducting a formal toxicity evaluation of DDBAC on honeybee mortality, we detected an accumulation of DDBAC in the honeybee midgut. We subsequently studied the midgut tissues of honeybees exposed to sub-lethal concentrations of DDBAC: histopathological examination revealed damage to midgut tissue upon DDBAC exposure, microbiome analysis showed a decreased abundance of beneficial midgut microbiota, lipidomics analysis revealed a significant reduction in cell membrane phospholipids with known functions in signal transduction, and a transcriptome analysis detected altered expression of genes involved in calcium signaling pathways (that variously function in calcium absorption, muscle contraction, and neurotransmission). Thus, our study establishes that DDBAC impacts honeybee midgut functions at multiple levels. Our study represents an early warning about the hazards of DDBAC and appeals for the proper stewardship of DDBAC to ensure the protection of our ecological environment.

Distribution and source identification of polychlorinated naphthalenes in bees, bee pollen, and wax from China.

Polychlorinated naphthalenes (PCNs) are highly toxic and persistent organic pollutants that can cause adverse effects in the environment and on human health. PCNs have been detected in remote areas because of their long-range transportation. Bees and bee products are commonly used as biomonitors for various pollutants in the environment. However, information on PCNs in apiaries is scarce. The aim of this study was to evaluate the occurrences of PCNs in bees and bee products from apiaries located in different geographical regions of China, and to identify potential pollution sources and assess exposure risks to humans. Our results showed that the average Σ75PCNs concentrations in bees, pollen, and wax were 74.1, 96.3, and 141 pg/g dry weight, respectively. The homologue and congener profiles of PCNs in bees, pollen, and wax were similar, and di- and tri-chlorinated naphthalenes (>60%) were the predominant homologues. The concentrations and distributions of PCNs in bees, pollen, and wax varied among different geographical regions, but their occurrences were correlated with PCN metallurgical sources in China. The health risks of PCNs in pollen were evaluated, and both carcinogenic and non-carcinogenic risks of PCNs exposure to humans through the diet were low.

Bisphenol F induces liver-gut alteration in zebrafish.

The unease of consumers with bisphenol A has led to the increased industrial usage of bisphenol F (BPF), which is a new hazard to environmental health. Here, zebrafish were exposed to three BPF concentrations (0.5, 5, and 50 µg/L) from the embryonic stage for 180 days. Results showed that zebrafish body length and weight decreased and hepatosomatic index values increased, even at environmentally relevant concentration. Histological analysis identified the occurrence of hepatic fibrosis and steatosis in 5 and 50 µg/L groups, which indicated the liver injury caused by BPF. Based on the untargeted metabolomics results, a dose-dependent variation in the effects of BPF on liver metabolism was found, and amino acids, purines and one carbon metabolism were the main affected processes in the 0.5, 5, and 50 µg/L treatments, respectively. At the same time, BPF induced a shift in intestinal microbiome composition, including decreased abundance of Erysipelotrichaceae, Rhodobacteraceae and Gemmobacter. In addition, the correlation analysis suggested an association between gut microbiome changes and affected hepatic metabolites after BPF exposure. These findings indicate that a liver-gut alteration is induced by long-term BPF exposure.

Acaricide flumethrin-induced sublethal risks in honeybees are associated with gut symbiotic bacterium Gilliamella apicola through microbe-host metabolic interactions.

Flumethrin is one of the few acaricides that permit the control of Varroa disease or varroosis in bee colonies. However, flumethrin accumulates in hive products. We previously discovered that sublethal doses of flumethrin induce significant physiological stress in honeybees (Apis mellifera L.), however its potential impacts on the honeybee gut microenvironment remains unknown. To fill this gap, honeybees were exposed to a field-relevant concentration of flumethrin (10 µg/L) for 14 d and its potential impacts on gut system were evaluated. The results indicated that flumethrin triggered immune responses in the gut but had limited effects on survival and gut microbial composition. However, survival stress drastically increased in bees exposed to antibiotics, suggesting that the gut microbiota is closely related to flumethrin-induced dysbiosis in the bee gut. Based on a non-targeted metabolomics approach, flumethrin at 10 µg/L considerably altered the composition of intestinal metabolites, and we discovered that this metabolic stress was closely linked with a reduction of gut core bacterial endosymbiont Gilliamella spp. through a combination of microbiological and metabolomics investigations. Finally, an in vitro study showed that while flumethrin does not directly inhibit the growth of Gilliamella apicola isolates, it does have a significant impact on the glycerophospholipid metabolism in bacteria cells, which was also observed in host bees. These findings indicated that even though flumethrin administered at environmental relevant concentrations does not significantly induce death in honeybees, it still alters the metabolism balance between honeybees and the gut symbiotic bacterium, G. apicola. The considerable negative impact of flumethrin on the honeybee gut microenvironment emphasizes the importance of properly monitoring acaricide to avoid potential environmental concerns, and further studies are needed to illustrate the mode of action of bee health-gut microbiota-exogenous pesticides.

Short- and medium-chain chlorinated paraffins in honey from China: Distribution, source analysis, and risk assessment.

Chlorinated paraffins (CPs) are industrial chemicals produced in large quantities. Short-chain CPs (SCCPs) were classified as persistent organic pollutants under the Stockholm Convention in 2017. Medium-chain CPs (MCCPs) became candidate persistent organic pollutants in 2021. CPs are now ubiquitously found in the environment. Honey bees can be exposed to CPs during foraging, and this exposure subsequently results in the contamination of honey and other bee products along with colony food production and storage. Here, SCCP and MCCP concentrations in honey collected from Chinese apiaries in 2015 and 2021 were determined. Total CP concentrations in honey from 2021 to 2015 were comparable, but the ratio of MCCPs/SCCPs was higher in 2021 than in 2015. SCCP and MCCP congener group profiles in all honey samples were similar and dominated by C10-11Cl6-7 and C14Cl6-7, respectively. MCCP concentrations were also higher than SCCP concentrations in bees, pollen, and wax but not in bee bread, which were all collected in 2021. The order of average CP concentrations was determined as wax > bee > pollen > bee bread > honey. Poor relationships were found between SCCP concentrations in honey and other samples, but a relationship between MCCP concentrations in honey and other samples was observed. Migration tests of CPs in plastic bottles showed essentially no migration into honey during storage. The risks to humans from CPs in honey are low.

Quizalofop-P-ethyl induced developmental toxicity and cardiotoxicity in early life stage of zebrafish (Danio rerio).

Quizalofop-P-ethyl (QpE), a highly efficient selective herbicide, has good control effect on annual and perennial weeds. However, its excessive use will pose a threat to the ecological environment. QpE has been proven harmful to aquatic organisms, but there is little evidence on the adverse effects of QpE in the early life of aquatic organisms. In this work, zebrafish (Danio rerio) embryos were treated with 0.10, 0.20, 0.30, 0.40, and 0.50 mg/L of QpE for 120 h. The findings revealed that the LC50 value of QpE to zebrafish embryos was 0.23 mg/L at 96 hpf. QpE exposure significantly increased the mortality rate, decreased the hatching rate and caused morphological defects during zebrafish embryonic development, with a concentration dependent manner. QpE also caused severe morphological changes in the cardiovascular system, as well as resulted in a dysfunction in cardiovascular performance. Meanwhile, both histopathological examination and neutrophil observations showed inflammatory response occurred in the heart. Furthermore, several genes associated with heart development and inflammation were significantly altered following QpE exposure. A protein-protein interaction (PPI) network analysis proved that there was a connection between the changed heart development-relevant and inflammation-related genes. Taken together, our findings suggest that QpE causes cardiotoxicity in zebrafish embryos by altering the expression of genes in the regulatory network of cardiac development, which might be aggravated by inflammatory reactions, thereby affecting embryo development. These findings generated here are useful for in-depth assessment of the effects of QpE on early development of aquatic organisms and providing theoretical foundation for risk management measures.

Bisphenol analogues induced metabolic effects through eliciting intestinal cell heterogeneous response.

The metabolic effects of endocrine-disrupting chemicals, such as bisphenol analogues, have drawn increasing attention. Bisphenol A (BPA) usage is associated with the occurrence of many metabolic diseases. With the restricted use of BPA, alternatives like bisphenol F (BPF) and bisphenol AF (BPAF) have been greatly introduced for industrial manufacture, and brings new hazard to public health. To understand how bisphenol analogues induced metabolic effects, zebrafish are continuous exposed to environmental level (0.5 µg/L) of BPA, BPF and BPAF since embryonic stage, and identified hepatic steatosis and insulin resistance at 60-day post fertilization. Hepatic transcriptional profile indicated that pancreatic disease pathways were activated by BPA, but were inhibited by BPF. At the same time, increased lipid secretion and gluconeogenesis pathways in zebrafish liver was found post BPAF exposure. Significant inflammatory response, histological injury and increased mucus secretion was detected in zebrafish intestine post exposure of three bisphenol analogues. Single-cell RNA sequencing of zebrafish intestinal cells revealed activation of lipid uptake and absorption pathways in enterocyte lineages, which well explained the hepatic steatosis induced by BPA and BPF. Besides, genes related to carbohydrate metabolism, diabetes and insulin resistance were activated in intestinal immune cell types by three bisphenol analogues. These findings indicated that BPA and its alternatives could lead to abnormal lipid and carbohydrate metabolism of zebrafish through inducing cell heterogeneous changes in gut, and revealed both molecular and cellular mechanism in mediating this effect.

Antibacterial Activity of Chinese Red Propolis against Staphylococcus aureus and MRSA.

The antibacterial activity of propolis has long been of great interest, and the chemical composition of propolis is directly dependent on its source. We recently obtained a type of propolis from China with a red color. Firstly, the antibacterial properties of this unusual propolis were determined against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). Studies on its composition identified and quantified 14 main polyphenols of Chinese red propolis extracts (RPE); quantification was carried out using liquid chromatography triple quadrupole tandem mass spectrometry (LC-QQQ-MS/MS) and RPE was found to be rich in pinobanksin, pinobanksin-3-acetate, and chrysin. In vitro investigations of its antibacterial activity revealed that its activity against S. aureus and MRSA is due to disruption of the cell wall and cell membrane, which then inhibits bacterial growth. Despite its similar antibacterial activities against S. aureus and MRSA, metabolomic analysis further revealed the effects of RPE on bacteria metabolism were different. The untargeted metabolomic results showed that a total of 7 metabolites in 12 metabolic pathways had significant changes (Fold change > 2, p < 0.05 *) after RPE treatment in S. aureus, while 11 metabolites in 9 metabolic pathways had significant changes (Fold change > 2, p < 0.05 *) after RPE treated on MRSA. Furthermore, RPE downregulated several specific genes related to bacterial biofilm formation, autolysis, cell wall synthesis, and bacterial virulence in MRSA. In conclusion, the data obtained indicate that RPE may be a promising therapeutic agent against S. aureus and MRSA.

Effects of dietary phosphatidylcholine and sphingomyelin on DSS-induced colitis by regulating metabolism and gut microbiota in mice.

Patients with inflammatory bowel diseases tend to show alteration of lipid profiles. It remains unknown whether dietary intake with specific lipids, such as phosphatidylcholine (PC) and sphingomyelin (SM), have distinguishable effects against IBD. Here, a preclinical study using dextran sulphate sodium (DSS)-induced colitis mice model was applied to explore/compare the effects by PC, and SM. Results showed that PC treatment (p.o., 30 mg/kg b.w., 15 d) exerted higher inhibitory activity than the same dosage of SM supplementation on colonic tissue lesions and pro-inflammatory cytokines expressions induced by DSS. Integrative analysis of the metabolome and microbiome indicated that PC and SM supplementation could modulate endogenous tryptophan metabolism, arginine and proline metabolism, purine metabolism, bile secretion, as well as vitamin digestion and absorption, closely correlated with their regulation on the abundance of Lactobacillus, Faecalibacterium, Dubosiella, Turicibacter, and Parasutterella communities in the gut. Based on these data, PC is a more promising candidate for preventing colitis than SM. Our findings provided a scientific foundation for further clinical research to screen more efficient dietary intervention strategy for colitis prevention.

Environmental level of bisphenol F induced reproductive toxicity toward zebrafish.

Bisphenol F (BPF), as an important bisphenol A substitute, is being increasingly used for industrial production. Here we performed large scale fecundity test for zebrafish that are continuous exposed to environmental levels of BPF (0.5, 5 and 50 µg/L) from embryonic stage, and identified suppressed spawning capacity of females and reduced fertility rate of males in adulthood. Although pathological change is only observed in female gonads, the transcriptional change in the hypothalamic-pituitary-gonad axis genes occurred in the gonads of both female and male fish at 150 days post-exposure. F1 generation embryos showed abnormal developmental outcomes including decreased heart rate, reduced body length, and inhibition of spontaneous movement after parental exposure to BPF. RNA-sequencing showed that the genes involved in skeletal/cardiac muscle development were significantly altered in F1 embryos spawned by BPF-treated zebrafish. The advanced pathway analysis showed that cancer and tumour formation were the most enriched pathways in the offspring of 0.5 and 5.0 µg/L groups; organismal development and cardiovascular system development were mainly affected after parental exposure to 50 µg/L of BPF; these changes were mediated by several involved regulators such as GATA4, MYF6, and MEF2C. These findings confirmed that long-term exposure to BPF at environment relevant concentration would result in reproductive toxicity among zebrafish indicating the urgent demand for the control of BPA substitutes.

Understanding the Gastrointestinal Protective Effects of Polyphenols using Foodomics-Based Approaches.

Plant polyphenols are rich sources of natural anti-oxidants and prebiotics. After ingestion, most polyphenols are absorbed in the intestine and interact with the gut microbiota and modulated metabolites produced by bacterial fermentation, such as short-chain fatty acids (SCFAs). Dietary polyphenols immunomodulatory role by regulating intestinal microorganisms, inhibiting the etiology and pathogenesis of various diseases including colon cancer, colorectal cancer, inflammatory bowel disease (IBD) and colitis. Foodomics is a novel high-throughput analysis approach widely applied in food and nutrition studies, incorporating genomics, transcriptomics, proteomics, metabolomics, and integrating multi-omics technologies. In this review, we present an overview of foodomics technologies for identifying active polyphenol components from natural foods, as well as a summary of the gastrointestinal protective effects of polyphenols based on foodomics approaches. Furthermore, we critically assess the limitations in applying foodomics technologies to investigate the protective effect of polyphenols on the gastrointestinal (GI) system. Finally, we outline future directions of foodomics techniques to investigate GI protective effects of polyphenols. Foodomics based on the combination of several analytical platforms and data processing for genomics, transcriptomics, proteomics and metabolomics studies, provides abundant data and a more comprehensive understanding of the interactions between polyphenols and the GI tract at the molecular level. This contribution provides a basis for further exploring the protective mechanisms of polyphenols on the GI system.