Resveratrol alleviates oxidative stress induced by oxidized soybean oil and improves gut function via changing gut microbiota in weaned piglets
Tóm tắt
Oxidized soybean oil (OSO) has been shown to impair growth and exacerbate inflammation, leading to intestinal barrier injury in animals. Recent evidence suggests important roles for resveratrol (RES) in the promoting growth performance, antioxidant capacity, anti-inflammatory, and regulate intestinal barriers in animals. Therefore, The objectives of this study are to investigate the effects of dietary RES (purity 98%) supplementation on the growth performance, antioxidant capacity, inflammatory state, and intestinal function of weaned piglets challenged with OSO. A total of 28 castrated weaned male piglets with a similar body weight of 10.19 ± 0.10 kg were randomly assigned to 4 dietary treatments for 28-d feeding trial with 7 replications per treatment and 1 piglet per replicate. Treatments were arranged as a 2 × 2 factorial with oil type [3% fresh soybean oil (FSO) vs. 3% OSO] and dietary RES (0 vs. 300 mg/kg). The results showed that relative to the FSO group, OSO stress tended to decrease the average daily feed intake (ADFI), and decreased the activity levels of lipase, villus/crypt ratio (VCR), the mRNA expression of FABP1, SOD2, IL-10 and ZO-1 in the jejunum, and SOD2, GPX1, occludin and ZO-1 in the colon, the levels of acetic acid in the colonic digesta, whereas up-regulated the mRNA expression of IL-1β and TNF-α in the jejunum (P < 0.05). Moreover, dietary supplementation with RES increased ether extract (EE), the activity levels of sucrase, lipase, α-amylase, villus height (VH) and VCR, the mRNA expression of FABP1, SOD2, IL-10 and occludin in the jejunum, and FABP1, PPAR-γ, GPX1, occludin and ZO-1 in the colon, and the abundance of Firmicutes, acetic and propionic acid, but decreased the levels of D-lactic acid in the plasma, the abundance of Bacteroidetes in the colonic digesta of weaned piglets compared to the non-RES group (P < 0.05). Meanwhile, in the interaction effect analysis, relative to the OSO group, dietary RES supplementation in the diets supplemented with OSO increased the activity levels of trypsin, VH in the jejunum, the abundance of Actinobacteria, the levels of butyric acid of weaned piglets, but failed to influence the activity levels of trypsin and VH, Actinobacteria abundance, the levels of butyric acid when diets were supplemented with FSO (interaction, P < 0.05). Relative to the OSO group, dietary RES supplementation in the diets supplemented with OSO decreased the activity levels of DAO in the plasma of weaned piglets but failed to influence the activity levels of DAO when diets were supplemented with FSO (interaction, P < 0.05). Relative to the FSO group, dietary RES supplementation in the diets supplemented with FSO decreased the level of propionic acid, whereas RES supplementation failed to influence the level of propionic acid when the diet was supplemented with OSO (interaction, P < 0.01). Inclusion of OSO intensified inflammatory states and impaired the intestinal health characteristics of weaned piglets. Dietary RES supplementation improved the antioxidant capacity, anti-inflammatory activity, and intestinal morphology. Further studies showed that the protective effects of RES on gut health could be linked to the decreased abundance of Prevotella_1, Clostridium_sensu_stricto_6, and Prevotellaceae_UCG003 and increased levels of acetic and propionic acid.
Tài liệu tham khảo
Fanalli SL, da Silva BPM, Petry B, Santana MHA, Polizel GHG, Antunesc RC, et al. Dietary fatty acids applied to pig production and their relation to the biological processes: A review. Livest Sci. 2022;265:105092. https://doi.org/10.1016/j.livsci.2022.105092.
Wealleans AL, Bierinckx K, Benedetto MD. Fats and oils in pig nutrition: Factors affecting digestion and utilization. Anim Feed Sci Tech. 2021;277:114950. https://doi.org/10.1016/j.anifeedsci.2021.114950.
Fanalli SL, da Silva BPM, Gomes JD, Ciconello FN, de Almeida VV, Freitas FAO, et al. Effect of dietary soybean oil inclusion on liver-related transcription factors in a pig model for metabolic diseases. Scientific Reports. 2022;12:10318. https://doi.org/10.1038/s41598-022-14069-1.
Kerr BJ, Kellner TA, Shurson GC. Characteristics of lipids and their feeding value in swine diets. J Anim Sci Biotechnol. 2015;6:30. https://doi.org/10.1186/s40104-015-0028-x.
Awada M, Soulage C, Meynier A, Debard C, Plaisancié P, Benoit B, et al. Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells. J Lipid Res. 2012;53(10):2069–80. https://doi.org/10.1194/jlr.m026179.
Liu P, Chen C, Kerr BJ, Weber TE, Johnston LJ, Shurson GC. Influence of thermally oxidized vegetable oils and animal fats on growth performance, liver gene expression, and liver and serum cholesterol and triglycerides in young pigs. J Anim Sci. 2014;92(7):2960–70. https://doi.org/10.2527/jas.2012-5709.
Tan L, Rong D, Yang Y, Zhang B. Effect of oxidized soybean oils on oxidative status and intestinal barrier function in broiler chickens. Braz J Poultry Sci. 2018;20(2):333–41. https://doi.org/10.1590/1806-9061-2017-0610.
Overholt MF, Dilger AC, Boler DD, Kerr BJ. Influence of feeding thermally peroxidized soybean oil on growth performance, digestibility, and gut integrity in finishing pigs. J Anim Sci. 2018;96(7):2789–803. https://doi.org/10.1093/jas/sky091.
Degroote J, Wang W, Vergauwen H, De Smet S, Van Ginneken C, Michiels J. Impact of a dietary challenge with peroxidized oil on the glutathione redox status and integrity of the small intestine in weaned piglets. Animal. 2019;13(8):1641–50. https://doi.org/10.1017/s1751731118003166.
Ng CY, Kamisah Y, Faizah O, Jaarin K. The role of repeatedly heated soybean oil in the development of hypertension in rats: association with vascular inflammation. Int J Exp Pathol. 2012;93(5):377–87. https://doi.org/10.1111/j.1365-2613.2012.00839.x.
Liang F, Jiang S, Mo Y, Zhou G, Yang L. Consumption of oxidized soybean oil increased intestinal oxidative stress and affected intestinal immune variables in yellow-feathered broilers. Asian Austral J Anim. 2015;28(8):1194–201. https://doi.org/10.5713/ajas.14.0924.
Martens EC, Mareike N, Desai MS. Interactions of commensal and pathogenic microorganisms with the intestinal mucosal barrier. Nat Rev Microbiol. 2018;16(8):457–70. https://doi.org/10.1038/s41579-018-0036-x.
Yan HL, Zhou P, Zhang Y, Zhang ZZ, Liu JB, Zhang HF. Short-chain fructo-oligosaccharides alleviates oxidized oil-induced intestinal dysfunction in piglets associated with the modulation of gut microbiota. J Funct Foods. 2020;64:103661. https://doi.org/10.1016/j.jff.2019.103661.
Zhou Z, Wang Y, Jiang Y, Diao Y, Strappe P, Prenzler P, et al. Deep-fried oil consumption in rats impairs glycerolipid metabolism, gut histology and microbiota structure. Lipids Health Dis. 2016;15(1):86. https://doi.org/10.1186/s12944-016-0252-1.
Zhang H, Chen YN, Chen YP, Ji SL, Jia PL, Li Y, et al. Comparison of the protective effects of resveratrol and pterostilbene against intestinal damage and redox imbalance in weanling piglets. J Anim Sci Biotechno. 2020;11:52. https://doi.org/10.1186/s40104-020-00460-3.
Wang DF, Zhou LL, Zhou HL, Hu HC, Hou GY. Chemical composition and protective effect of guava (Psidium guajava L.) leaf extract on piglet intestines. J Sci Food Agr. 2021;101(7):2767–78. https://doi.org/10.1002/jsfa.10904.
Zhang C, Luo JQ, Yu B, Zheng P, Huang ZQ, Mao XB, et al. Dietary resveratrol supplementation improves meat quality of finishing pigs through changing muscle fiber characteristics and antioxidative status. Meat Sci. 2015;102:15–21. https://doi.org/10.1016/j.meatsci.2014.11.014.
Chen XL, Zeng ZY, Huang ZQ, Chen DW, He J, Chen H, et al. Effects of dietary resveratrol supplementation on immunity, antioxidative capacity and intestinal barrier function in weaning piglets. Anim Biotechnol. 2021;32(2):240–5. https://doi.org/10.1080/10495398.2019.1683022.
Meng QW, Guo T, Li GQ, Sun SS, He SQ, Cheng BJ, et al. Dietary resveratrol improves antioxidant status of sows and piglets and regulates antioxidant gene expression in placenta by keap1-nrf2 pathway and sirt1. J Anim Sci Biotechnol. 2018;9:34. https://doi.org/10.1186/s40104-018-0248-y.
Gan ZD, Wei WY, Li Y, Wu JM, Zhao YW, Zhang LL, et al. Cumin and resveratrol regulate intestinal bacteria and alleviate intestinal inflammation in weaned piglets. Molecules. 2019;24(7):1220. https://doi.org/10.3390/molecules24071220.
Shen L, Ji HF. Reciprocal Interactions Between Resveratrol and gut microbiota deepen our understanding of molecular mechanisms underlying its health benefits. Trends Food Sci Technol. 2018;81:232–6. https://doi.org/10.1016/j.tifs.2018.09.026.
Fu QY, Tan Z, Shi LG, Xun WJ. Resveratrol attenuates diquat-induced oxidative stress by regulating gut microbiota and metabolome characteristics in piglets. Front Microbiol. 2021;12:695155. https://doi.org/10.3389/fmicb.2021.695155.
Meng Q, Sun S, Bai Y, Luo Z, Shan A. Effects of dietary resveratrol supplementation in sows on antioxidative status, myofiber characteristic and meat quality of offspring. Meat Sci. 2020;167:108176. https://doi.org/10.1016/j.meatsci.2020.108176.
AOCS. Official Method Cd 8b-90 Peroxide value acetic acid-isooctane method. Champaign: American Oil Chemists Society. Revised 2003.
Rosero DS, Odle J, Moeser AJ, Boyd RD, Van Heugten E. Peroxidised dietary lipids impair intestinal function and morphology of the small intestine villi of nursery pigs in a dose-dependent manner. Br J Nutr. 2015;114(12):1985–92. https://doi.org/10.1017/S000711451500392X.
Sebastian A, Ghazani SM, Marangoni AG. Quality and safety of frying oils used in restaurants. Food Res Int. 2014;64:420–3. https://doi.org/10.1016/j.foodres.2014.07.033.
NRC. Nutrient requirements of swine. Eleventh Revised Edition. Washington, DC: The National Academy Press; 2012. https://doi.org/10.17226/13298.
Meng QW, Wang LS, Sun SS, Shi Z, Su BC, Qu Z, et al. The influence of dietary corn distillers dried grains with solubles during gestation of sows on fatty acid composition of colostrum and offspring. Can J Anim Sci. 2019;99(4):812–9. https://doi.org/10.1139/cjas-2017-0131.
Walsh AM, Sweeney T, O’Shea CJ, Doyle DN, O’Doherty JV. Effect of supplementing varying inclusion levels of laminarin and fucoidan on growth performance, digestibility of diet components, selected faecal microbial populations and volatile fatty acid concentrations in weaned pigs. Anim Feed Sci Technol. 2013;183(3):151–9. https://doi.org/10.1016/j.anifeedsci.2013.04.013.
Huang SB, Cui ZJ, Hao XY, Cheng CH, Chen JZ, et al. Dietary fibers with low hydration properties exacerbate diarrhea and impair intestinal health and nutrient digestibility in weaned piglets. J Anim Sci Biotechno. 2022;13:142. https://doi.org/10.1186/s40104-022-00771-7.
Ren P, Zhu ZP, Dong B, Zang JJ, Gong LM. Determination of energy and amino acid digestibility in growing pigs fed corn distillers' dried grains with solubles containing different lipid levels. Arch Anim Nutr. 2011;65(4):303–19. https://doi.org/10.1080/1745039x.2011.588849.
Standardization Administration of China (SAC). Determination of Ash Insoluble in Hydrochloric Acid. Beijing: China Standard Press; 2009.
Standardization Administration of China (SAC). Determination of moisture and other volatile mater content in feeds. Beijing: China Standard Press; 2006.
Standardization Administration of China (SAC). Method for the determination of crude protein in feedstuffs. Beijing: China Standard Press; 1994.
Standardization Administration of China (SAC). Feeding stuffs Determination of crude fiber content Method with intermediate filtration. Beijing: China Standard Press; 2006.
Standardization Administration of China (SAC). Determination of crude fat in feeds. Beijing: China Standard Press; 2006.
Meng Q, Sun S, He S, Shi B, Shan A, Cheng B. Maternal dietary resveratrol alleviates weaning-associated intestinal inflammation and diarrhea in porcine offspring by altering intestinal gene expression and microbiota. Food Funct. 2019;10(9):5626–43.
Teng T, Gao F, He W, Fu HY, Shi BM. An early fecal microbiota transfer improves the intestinal conditions on microflora and immunoglobulin and antimicrobial peptides in piglets. J Agric Food Chem. 2020;68(17):4830–43. https://doi.org/10.1021/acs.jafc.0c00545.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative pcr and the 2(t)(-delta delta c) method. Methods. 2001;25(4):402–8. https://doi.org/10.1006/meth.2001.1262.
Fang J, Shi BM, He W, Qin XT, Wang L, Wang FC, et al. Effects of fermented wheat bran on growth performance, nutrient apparent digestibility, immune function and fecal microbiota of weaned piglets. Chin J Anim Nutr. 2022;34(1):150–8. https://doi.org/10.3969/j.issn.1006-267x.2022.01.016.
Kerr BJ, Lindblom SC, Overholt MF. Influence of feeding thermally peroxidized soybean oil on growth performance, digestibility, gut integrity, and oxidative stress in nursery pigs. J Anim Sci. 2020;98(2):1–11. https://doi.org/10.1093/jas/skaa016.
Luo B, Chen D, Tian G, Zheng P, Yu B. Effects of dietary aged maize with oxidized fish oil on growth performance, antioxidant capacity and intestinal health in weaned piglets. Animals. 2019;9(9):624. https://doi.org/10.3390/ani9090624.
Gao F, Wang WQ, Zhang WT, Shi BM. Effects of oxidized soybean oil on the performance of sows and jejunum health of suckling piglets. J Anim Physiol An N. 2022. https://doi.org/10.1111/jpn.13774.
Dalle-donne I, Rossi R, Colombo R, Daniela G, Aldo M. Biomarkers of oxidative damage in human disease. Clin Chem. 2006;52(4):601–23. https://doi.org/10.1373/clinchem.2005.061408.
Zeng Z, Chen X, Huang Z, Chen D, He J, Chen H, et al. Effects of dietary resveratrol supplementation on growth performance and muscle fiber type transformation in weaned piglets. Anim Feed Sci Techno. 2020;265:114499.
Zhang HZ, Chen DW, He J, Zheng P, Yu J, Mao XB, et al. Long-term dietary resveratrol supplementation decreased serum lipids levels, improved intramuscular fat content, and changed the expression of several lipid metabolism-related miRNAs and genes in growing-finishing pigs. J Anim Sci. 2019;97(4):1745–56. https://doi.org/10.1093/jas/skz057.
Koo B, Nyachoti CM. Effects of thermally oxidized canola oil and tannic acid supplementation on nutrient digestibility and microbial metabolites in finishing pigs. J Anim Sci. 2019;97(6):2468–78. https://doi.org/10.1093/jas/skz104.
Gan Z, Wei W, Wu J, Zhao Y, Zhang L, Wang T, et al. Resveratrol and curcumin improve intestinal mucosal integrity and decrease m(6)A RNA methylation in the intestine of weaning piglets. ACS Omega. 2019;4(17):17438–46. https://doi.org/10.1021/acsomega.9b02236.
Kanazawa K, Ashida H, Minamoto S, Danno GI, Natake M. The effects of orally administered linoleic acid and its autoxidation products on intestinal mucosa in rat. J Nutr Sci Vitaminol. 1988;34(4):363–73. https://doi.org/10.1016/0306-9192(88)90061-9.
Kimura F, Okayasu I, Kakinuma H, Satoh Y, Kuwao S, Saegusa M, et al. Differential diagnosis of reactive mesothelial cells and malignant mesothelioma cells using the cell proliferation markers minichromosome maintenance protein 7, geminin, topoisomerase ii alpha and ki-67. Acta Cytol. 2013;57(4):384. https://doi.org/10.1159/000350262.
Wang L, Yan S, Li J, Li Y, Deng X, Yin J, et al. Rapid communication: The relationship of enterocyte proliferation with intestinal morphology and nutrient digestibility in weaning piglets. J Anim Sci. 2019;97(1):353–8. https://doi.org/10.1093/jas/sky388.
Ang Z, Ding JL. GPR41 and GPR43 in obesity and inflammation-protective or causative. Front Immunol. 2016;7:28. https://doi.org/10.3389/fimmu.2016.00028.
Sun M, Wu W, Liu Z, Cong YZ. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J Gastroenterol. 2017;52:1–8. https://doi.org/10.1007/s00535-016-1242-9.
Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun. 2013;4:1829. https://doi.org/10.1038/ncomms2852.
Ryan KK, Li B, Grayson BE, Matter EK, Woods SC, Seeley RJ. A role for central nervous system PPAR-γ in the regulation of energy balance. Nat Med. 2011;17(5):623–6. https://doi.org/10.1038/nm.2349.
Mao H, Xu X, Liu H, Cao H, Dong X, Xu N, et al. The temporal-spatial patterns, polymorphisms and association analysis with meat quality traits of FABP1 gene in domestic pigeons (Columba livia). Brit Poultry Sci. 2020;61(3):232–41. https://doi.org/10.1080/00071668.2020.1724880.
Danielewski M, Matuszewska A, Szelag A, Sozanski T. The impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis. Int J Mol Sci. 2021;22(11):6074. https://doi.org/10.3390/ijms22116074.
Sun SS, Meng QW, Luo Z, Shi BM, Bi CP, Shan AS. Effects of dietary resveratrol supplementation during gestation and lactation of sows on milk composition of sows and fat metabolism of sucking piglets. J Anim Physiol An N. 2019;103(3):813–21. https://doi.org/10.1111/jpn.13064.
Faghihzadeh F, Hekmatdoost A, Adibi P. Resveratrol and liver: a systematic review. J Res Med Sci. 2015;20(8):797–810. https://doi.org/10.4103/1735-1995.168405.
Ransy C, Vaz C, Lombès A, Bouillaud F. Use of H2O2 to cause oxidative stress, the catalase Issue. Int J Mol Sci. 2020;21(23):9149. https://doi.org/10.3390/ijms21239149.
Liao SF, Nyachoti M. Using probiotics to improve swine gut health and nutrient utilization. Anim Nutr. 2017;3(04):331–43. https://doi.org/10.1016/j.aninu.2017.06.007.
De M, Gabler NK. Investigating the relationship between nursery pig performance and markers of intestinal morphology and integrity. J Anim Sci. 2021;99(Suppl 1):100. https://doi.org/10.1093/jas/skab054.161.
Bernotti S, Seidman E, Sinnett D, Brunet S, Dionne S, Delvin E, et al. Inflammatory reaction without endogenous antioxidant response in Caco-2 cells exposed to iron/ascorbate-mediated lipid peroxidation. Am J Physiol Gastrointest Liver Physiol. 2003;285(5):G898. https://doi.org/10.1152/ajpgi.00042.2003.
Fukudome I, Kobayashi M, Dabanaka K, Maeda H, Okamoto K, Okabayashi T, et al. Diamine oxidase as a marker of intestinal mucosal injury and the effect of soluble dietary fiber on gastrointestinal tract toxicity after intravenous 5-fluorouracil treatment in rats. Med Mol Morphol. 2014;47(2):100–7. https://doi.org/10.1007/s00795-013-0055-7.
Szalay L, Umar F, Khadem A, Jafarmadar M, Furst W, Ohlinger W, et al. Increased plasma d-lactate is associated with the severity of hemorrhagic/traumatic shock in rats. Shock. 2003;20(3):245–50. https://doi.org/10.1097/00024382-200309000-00008.
Qiu Y, Yang J, Wang L, Yang X, Gao K, Zhu C, et al. Dietary resveratrol attenuation of intestinal inflammation and oxidative damage is linked to the alteration of gut microbiota and butyrate in piglets challenged with deoxynivalenol. J Anim Sci Biotechnol. 2021;12(4):17. https://doi.org/10.1186/s40104-021-00596-w.
Zihni C, Mills C, Matter K, Balda MS. Tight junctions: From simple barriers to multifunctional molecular gates. Nat Rev Mol Cell Biol. 2016;17(9):564–80. https://doi.org/10.1038/nrm.2016.80.
Wang N, Han Q, Wang G, Ma WP, Wang J, Wu WX, et al. Resveratrol protects oxidative stress-induced intestinal epithelial barrier dysfunction by upregulating heme oxygenase-1 expression. Dig Dis Sci. 2016;61(9):2522–34. https://doi.org/10.1007/s10620-016-4184-4.
Zhou J, Xiong X, Wang KX, Zou LJ, Ji P, Yin YL. Ethanolamine enhances intestinal functions by altering gut microbiome and mucosal anti-stress capacity in weaned rats. Br J Nutr. 2018;120(3):241–9. https://doi.org/10.1017/s0007114518001101.
Collado MC, Isolauri E, Laitinen K, Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr. 2008;88(4):894–9. https://doi.org/10.1186/1550-2783-5-15.
Zhang C, Luo JQ, Yu B, Chen J, Chen D. Effects of resveratrol on lipid metabolism in muscle and adipose tissues: A reevaluation in a pig model. J Funct Foods. 2015;14:590–5. https://doi.org/10.1016/j.jff.2015.02.039.
Duncan SH, Louis P, Flint HJ. Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. Appl Environ Microbiol. 2004;70:5810–7. https://doi.org/10.1128/aem.70.10.5810-5817.2004.
Xiao Y, Yan H, Diao H, Yu B, He J, Yu J, et al. Gut Microbiota Intervention Suppresses DSS-Induced Inflammatory Responses by Deactivating TLR/NLR Signalling in Pigs. Sci Rep. 2017;7:3224. https://doi.org/10.1038/s41598-017-03161-6.
Chang TT, Chen JW. Direct CCL4 inhibition modulates gut microbiota, reduces circulating trimethylamine N-Oxide, and improves glucose and lipid metabolism in high-fat-diet-induced diabetes mellitus. J Inflamm Res. 2021;11:27. https://doi.org/10.2147/jir.s343491.
Alrafas HR, Busbee PB, Chitrala KN, Nagarkatti M, Nagarkatti P. Alterations in the gut microbiome and suppression of histone deacetylases by resveratrol are associated with atten uation of colonic inflammation and protection against colorectal cancer. J Clin Med. 2020;9(6):1796. https://doi.org/10.3390/jcm9061796.
Zou X, Ji J, Qu H, Wang J, Shu DM, Wang Y, et al. Effects of sodium butyrate on intestinal health and gut microbiota composition during intestinal inflammation progression in broilers. Poult Sci. 2019;98(10):4449–56. https://doi.org/10.3382/ps/pez279.
Andon A, Tsujikawa T, Fujiyama Y. Role of dietary fiber and short-chain fatty acids in the colon. Curr Pharm Des. 2003;9(4):347–58. https://doi.org/10.2174/1381612033391973.
Cui Q, Fu Q, Zhao X, Ma WP, Wang J, Wu WX, et al. Protective effects and immunomodulation on piglets infected with rotavirus following resveratrol supplementation. PLoS One. 2018;13(2):e0192692. https://doi.org/10.1371/journal.pone.0192692.
Abdul-Wahab OMS, Al-Shyarba MH, Mardassi BB, Sassi N, Al Fayi MSS, Otifi H, et al. Molecular detection of urogenital mollicutes in patients with invasive malignant prostate tumor. Infect Agents Cancer. 2021;16(1):6. https://doi.org/10.1186/s13027-021-00344-9.
Signorelli P, Ghidoni R. Resveratrol as an anticancer nutrient: molecular basis, open questions and promises. J Nutr Biochem. 2005;16:449–66. https://doi.org/10.1016/j.jnutbio.2005.01.017.
Trincheri NF, Nicotra G, Follo C, Castino R, Isidoro C. Resveratrol induces cell death in colorectal cancer cells by a novel pathway involving lysosomal cathepsin D. Carcinogenesis. 2007;28:922–31. https://doi.org/10.1093/carcin/bgl223.
Saltiel E. Clostridium difficile-Associated Diarrhea: Role of the pharmacist in the health system. J Pharm Pract. 2013;26(5):462–3. https://doi.org/10.1177/0897190013499520.
Wang K, Liao M, Zhou N, Bao L, Ma K, Zheng Z, et al. Parabacteroides distasonis alleviates obesity and metabolic dysfunctions via production of succinate and secondary bile acids. Cell Reports. 2019;26(1):222-35. e225. https://doi.org/10.1016/j.celrep.2018.12.028.