Association of dietary intake of polyphenols, lignans, and phytosterols with immune-stimulating microbiota and COVID-19 risk in a group of Polish men and women
Agnieszka Micek, Izabela Bolesławska, Paweł Jagielski, Kamil Konopka, Anna Waśkiewicz, Anna Maria Witkowska, Juliusz Przysławski, Justyna Godos
Frontiers in Nutrition, doi:10.3389/fnut.2023.1241016
Objectives: Devastating consequences of COVID-19 disease enhanced the role of promoting prevention-focused practices. Among targeted efforts, diet is regarded as one of the potential factors which can affect immune function and optimal nutrition is postulated as the method of augmentation of people's viral resistance. As epidemiological evidence is scarce, the present study aimed to explore the association between dietary intake of total polyphenols, lignans and plant sterols and the abundance of immunomodulatory gut microbiota such as Enterococcus spp. and Escherichia coli and the risk of developing COVID-19 disease. Methods: Demographic data, dietary habits, physical activity as well as the composition of body and gut microbiota were analyzed in a sample of 95 young healthy individuals. Dietary polyphenol, lignan and plant sterol intakes have been retrieved based on the amount of food consumed by the participants, the phytochemical content was assessed in laboratory analysis and using available databases. Results: For all investigated polyphenols and phytosterols, except campesterol, every unit increase in the tertile of intake category was associated with a decrease in the odds of contracting COVID-19. The risk reduction ranged from several dozen percent to 70 %, depending on the individual plant-based chemical, and after controlling for basic covariates it was statistically significant for secoisolariciresinol (OR = 0.28, 95% CI: 0.11-0.61), total phytosterols (OR = 0.47, 95% CI: 0.22-0.95) and for stigmasterols (OR = 0.34, 95% CI: 0.14-0.72). We found an inverse association between increased β-sitosterol intake and phytosterols in total and the occurrence of Escherichia coli in stool samples outside reference values, with 72% (OR = 0.28, 95% CI: 0.08-0.86) and 66% (OR = 0.34, 95% CI: 0.10-1.08) reduced odds of abnormal level of bacteria for the highest compared with the lowest tertile of phytochemical consumption. Additionally, there was a
Ethics statement The studies involving human participants were reviewed and approved by the Bioethics Committee of Jagiellonian University No. 1072.6120.5.2020 and 1072.6120.202.2019. The patients/participants provided their written informed consent to participate in this study.
Author contributions AM, PJ, IB, and JG contributed to conception and design of the study. AM, IB, and JG wrote the first draft of the manuscript. AM performed the statistical analysis. PJ, AW, and AMW investigation. AM, IB, PJ, KK, AW, AMW, JP, and JG wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnut.2023.1241016/ full#supplementary-material
References
Akkuş, Atalay, Parlak, COVID-19 pandemic: changes in the emotions, body weights and nutrition habits of individuals during social intervention measures, Med J Nutrition Metab,
doi:10.3233/MNM-210006Allam, Amen, Ashour, Assaf, Hassan et al., In silico study of natural compounds from sesame against COVID-19 by targeting Mpro, PLpro and RdRp, RSC Adv,
doi:10.1039/d1ra03937gAlwani, Yassin, Al-Zoubi, Aboumarzouk, Nettleship et al., Sex-based differences in severity and mortality in COVID-19, Rev Med Virol,
doi:10.1002/rmv.2223Andriamiarina, Laraki, Pelletier, Debry, Effects of stigmasterolsupplemented diets on fecal neutral sterols and bile acid excretion in rats, Ann Nutr Metab,
doi:10.1159/000177548Annunziata, Zamparelli, Santoro, Ciampaglia, Stornaiuolo et al., May polyphenols have a role against coronavirus infection? An overview of in vitro evidence, Front Med (Lausanne),
doi:10.3389/fmed.2020.00240Bajpai, Shukla, Paek, Lim, Kumar et al., Efficacy of (+)-Lariciresinol to control bacterial growth of Staphylococcus aureus and Escherichia coli O157:H7, Front Microbiol,
doi:10.3389/fmicb.2017.00804Barre, Van Damme, Simplicien, Poder, Klonjkowski et al., Man-specific lectins from plants, fungi, algae and cyanobacteria, as potential blockers for SARS-CoV, MERS-CoV and SARS-CoV-2 (COVID-19) coronaviruses: biomedical perspectives, Cells,
doi:10.3390/cells10071619Bonaccio, Gianfagna, Stival, Amerio, Bosetti et al., Changes in a Mediterranean lifestyle during the COVID-19 pandemic among elderly Italians: an analysis of gender and socioeconomic inequalities in the "LOST in Lombardia" study, Int J Food Sci Nutr,
doi:10.1080/09637486.2022.2040009Bonaccio, Pounis, Cerletti, Donati, Iacoviello et al., Mediterranean diet, dietary polyphenols and low grade inflammation: results from the MOLI-SANI study, Med J Nutrition Metab,
doi:10.3233/MNM-200597Boto-Ordóñez, Urpi-Sarda, Queipo-Ortuño, Tulipani, Tinahones, Andres-Lacueva C. High levels of Bifidobacteria are associated with increased levels of anthocyanin microbial metabolites: a randomized clinical trial, Food Funct,
doi:10.1039/c4fo00029cBrito, Zang, A review of lignan metabolism, milk enterolactone concentration, and antioxidant status of dairy cows fed flaxseed, Molecules,
doi:10.3390/molecules24010041Cai, Wu, Zhang, Lignans from Mosla scabra ameliorated influenza a virus-induced pneumonia via inhibiting macrophage activation, Evid Based Complement Alternat Med,
doi:10.1155/2022/1688826Cao, Ou, Chen, Zhang, Szkudelski et al., Dietary polyphenols and type 2 diabetes: human study and clinical trial, Crit Rev Food Sci Nutr,
doi:10.1080/10408398.2018.1492900Cherian, Vadivel, Thiruganasambandham, Madhavankutty, Phytocompounds and their molecular targets in immunomodulation: a review, J Basic Clin Physiol Pharmacol,
doi:10.1515/jbcpp-2021-0172Dai, Tan, Ren, Shao, Tao et al., COVID-19 risk appears to vary across different alcoholic beverages, Front Nutr,
doi:10.3389/fnut.2021.772700Ebrahimzadeh-Attari, Panahi, Hebert, Ostadrahimi, Saghafi-Asl et al., Nutritional approach for increasing public health during pandemic of COVID-19: a comprehensive review of antiviral nutrients and nutraceuticals, Health Promot Perspect,
doi:10.34172/hpp.2021.17Enaru, Socaci, Farcas, Socaciu, Danciu et al., Novel delivery systems of polyphenols and their potential health benefits, Pharmaceuticals (Basel),
doi:10.3390/ph14100946Fraga, Croft, Kennedy, Tomás-Barberán, The effects of polyphenols and other bioactives on human health, Food Funct,
doi:10.1039/c8fo01997eGallagher, Heymsfield, Heo, Jebb, Murgatroyd et al., Healthy percentage body fat ranges: an approach for developing guidelines based on body mass index, Am J Clin Nutr,
doi:10.1093/ajcn/72.3.694Gałecka, Basińska, Bartnicka, Znaczenie mikrobioty jelitowej w kształtowaniu zdrowia człowieka-implikacje w praktyce lekarza rodzinnego, Forum Medycyny Rodzinnej
Giovinazzo, Gerardi, Uberti-Foppa, Lopalco, Can natural polyphenols help in reducing cytokine storm in COVID-19 patients? Molecules,
doi:10.3390/molecules25245888Gliozzi, Walker, Muscoli, Vitale, Gratteri et al., Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia, Int J Cardiol,
doi:10.1016/j.ijcard.2013.08.125Godos, Vitale, Micek, Ray, Martini et al., Dietary polyphenol intake, blood pressure, and hypertension: a systematic review and meta-analysis of observational studies, Antioxidants (Basel),
doi:10.3390/antiox8060152Grosso, Godos, Currenti, Micek, Falzone et al., The effect of dietary polyphenols on vascular health and hypertension: current evidence and mechanisms of action, Nutrients,
doi:10.3390/nu14030545Grosso, Godos, Lamuela-Raventos, Ray, Micek et al., A comprehensive meta-analysis on dietary flavonoid and lignan intake and cancer risk: level of evidence and limitations, Mol Nutr Food Res,
doi:10.1002/mnfr.201600930Grosso, Micek, Godos, Pajak, Sciacca et al., Dietary flavonoid and lignan intake and mortality in prospective cohort studies: systematic review and dose-response meta-analysis, Am J Epidemiol,
doi:10.1093/aje/kww207Gu, Zhao, Yang, Du, Li et al., A new perspective to improve the treatment of Lianhuaqingwen on COVID-19 and prevent the environmental health risk of medication, Environ Sci Pollut Res Int,
doi:10.1007/s11356-022-21125-wJagielski, Wnęk, Łuszczki, Bolesławska, Micek et al., Proposition of a new POLA index to assess the immunomodulatory properties of the diet and its relationship with the gut microbiota, using the example of the incidence of COVID-19 in a Group of People without comorbidities, Nutrients,
doi:10.3390/nu14204227Jagielski, Łuszczki, Wnęk, Micek, Bolesławska et al., Associations of nutritional behavior and gut microbiota with the risk of COVID-19 in healthy young adults in Poland, Nutrients,
doi:10.3390/nu14020350Khan, Nath, Rauf, Emran, Mitra et al., Multifunctional roles and pharmacological potential of β-sitosterol: emerging evidence toward clinical applications, Chem Biol Interact,
doi:10.3390/ph15101225Khan, Siddiqui, Beta-sitosterol: as immunostimulant, antioxidant and inhibitor of SARS-CoV-2 spike glycoprotein, Arch Pharmacol Ther,
doi:10.33696/Pharmacol.2.014Koistinen, Tuomainen, Lehtinen, Peltola, Auriola et al., Side-stream products of malting: a neglected source of phytochemicals, NPJ Sci Food,
doi:10.1038/s41538-020-00081-0Kočar, Režen, Rozman, Cholesterol, lipoproteins, and COVID-19: basic concepts and clinical applications, Biochim Biophys Acta Mol Cell Biol Lipids,
doi:10.1016/j.bbalip.2020.158849Li, Xin, Mo, Marozik, He et al., The bioavailability and biological activities of phytosterols as modulators of cholesterol metabolism, Molecules,
doi:10.3390/molecules27020523López-García, Cilla, Barberá, Alegría, Anti-inflammatory and cytoprotective effect of plant sterol and Galactooligosaccharides-enriched beverages in Caco-2 cells, J Agric Food Chem,
doi:10.1021/acs.jafc.9b03025Magrone, Jirillo, The interplay between the gut immune system and microbiota in health and disease: nutraceutical intervention for restoring intestinal homeostasis, Curr Pharm Des,
doi:10.2174/138161213804805793Merino, Joshi, Nguyen, Leeming, Mazidi et al., Diet quality and risk and severity of COVID-19: a prospective cohort study, Gut,
doi:10.1136/gutjnl-2021-325353Micek, Godos, Brzostek, Gniadek, Favari et al., Dietary phytoestrogens and biomarkers of their intake in relation to cancer survival and recurrence: a comprehensive systematic review with meta-analysis, Nutr Rev,
doi:10.1093/nutrit/nuaa043Micek, Godos, Rio, Galvano, Grosso, Dietary flavonoids and cardiovascular disease: a comprehensive dose-response meta-analysis, Mol Nutr Food Res,
doi:10.1002/mnfr.202001019Mileo, Nisticò, Miccadei, Polyphenols: immunomodulatory and therapeutic implication in colorectal cancer, Front Immunol,
doi:10.3389/fimmu.2019.00729Mohajeri, Mohajery, Nemati, Pourfarzi, The difference in the dietary inflammatory index, functional food, and antioxidants intake between COVID -19 patients and healthy persons, Med J Nutrition Metab,
doi:10.3233/MNM-211521Muller, Walker, Brauer, Sanduzzi Zamparelli, Capitelli et al., A phase II study on the effect of Taurisolo ® administered via AEROsol in hospitalized patients with mild to moderate COVID-19 pneumonia: the TAEROVID-19 study, J Inst Brew,
doi:10.3390/cells11091499Name, Souza, Vasconcelos, Prado, Pereira, Zinc, vitamin D and vitamin C: perspectives for COVID-19 with a focus on physical tissue barrier integrity, Front Nutr,
doi:10.3389/fnut.2020.606398Ngwa, Kumar, Thompson, Lyerly, Moore et al., Potential of flavonoid-inspired phytomedicines against COVID-19, Molecules,
doi:10.3390/molecules25112707O'driscoll, Santos, Wang, Cummings, Azman et al., Age-specific mortality and immunity patterns of SARS-CoV-2, Nature,
doi:10.1038/s41586-020-2918-0Palacios-Rápalo, Jesús-González, Cordero-Rivera, Morales, Osuna-Ramos et al., Cholesterol-rich lipid rafts as platforms for SARS-CoV-2 entry, Front Immunol,
doi:10.3389/fimmu.2021.796855Paraiso, Revel, Stevens, Ubani, Agwom et al., Molecular docking analysis of some phytochemicals on two SARS-CoV-2 targets, Curr Opin Food Sci,
doi:10.1101/2020.03.31.017657Pellegrini, Valtueña, Ardigò, Brighenti, Franzini et al., Intake of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol in relation to vascular inflammation and endothelial dysfunction in middle age-elderly men and post-menopausal women living in northern Italy, Nutr Metab Cardiovasc Dis,
doi:10.1016/j.numecd.2009.02.003Plat, Nichols, Mensink, Plant sterols and stanols: effects on mixed micellar composition and LXR (target gene) activation, J Lipid Res,
doi:10.1194/jlr.M500272-JLR200Plösch, Kruit, Bloks, Huijkman, Havinga et al., Reduction of cholesterol absorption by dietary plant sterols and stanols in mice is independent of the Abcg5/8 transporter, J Nutr,
doi:10.1093/jn/136.8.2135Pounis, Bonaccio, Castelnuovo, Costanzo, De Curtis et al., Polyphenol intake is associated with low-grade inflammation, using a novel data analysis from the Moli-sani study, Thromb Haemost,
doi:10.1160/TH15-06-0487Queipo-Ortuño, Boto-Ordóñez, Murri, Gomez-Zumaquero, Clemente-Postigo et al., Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers, Am J Clin Nutr,
doi:10.3945/ajcn.111.027847Salehi, Quispe, Sharifi-Rad, Martins, Nigam et al., Phytosterols: from preclinical evidence to potential clinical applications, Front Pharmacol,
doi:10.3389/fphar.2020.599959Shakoor, Feehan, Apostolopoulos, Platat, Dhaheri et al., Immunomodulatory effects of dietary polyphenols, Nutrients,
doi:10.3390/nu13030728Shokry, Hegazy, Abbas, Mostafa, Eissa et al., Phytoestrogen β-sitosterol exhibits potent in vitro antiviral activity against influenza a viruses. Vaccines (Basel),
doi:10.3390/vaccines11020228Stromsnes, Lagzdina, Olaso-Gonzalez, Gimeno-Mallench, Gambini, Pharmacological properties of polyphenols: bioavailability, mechanisms of action, and biological effects in in vitro studies, animal models, and humans, Biomedicine,
doi:10.3390/biomedicines9081074Sureja, Shah, Gajjar, Jadeja, Bodiwala et al., -silico computational investigations of AntiViral lignan derivatives as potent inhibitors of SARS CoV-2,
doi:10.1002/slct.202202069Van Laren, Drießen, Rasa, Massar, Hoor, Nutritional changes during the COVID-19 pandemic: a rapid scoping review on the impact of psychological factors, Int J Food Sci Nutr,
doi:10.1080/09637486.2023.2180613Venzon, Bernard-Raichon, Klein, Axelrad, Zhang et al., Gut microbiome dysbiosis during COVID-19 is associated with increased risk for bacteremia and microbial translocation, BioRxiv,
doi:10.1101/2021.07.15.452246Vezza, Canet, De Marañón, Bañuls, Rocha et al., Phytosterols: nutritional health players in the management of obesity and its related disorders. Antioxidants (Basel),
doi:10.3390/antiox9121266Vu, Rydland, Achenbach, Van Horn, Cornelis, Dietary Behaviors and incident COVID-19 in the UK biobank, Nutrients,
doi:10.3390/nu13062114Waśkiewicz, Zujko, Szcześniewska, Tykarski, Kwaśniewska et al., Polyphenols and dietary antioxidant potential, and their relationship with arterial hypertension: a cross-sectional study of the adult population in Poland (WOBASZ II), Adv Clin Exp Med,
doi:10.17219/acem/91487Witkowska, Waśkiewicz, Zujko, Mirończuk-Chodakowska, Cicha-Mikołajczyk et al., Assessment of plant sterols in the diet of adult polish population with the use of a newly developed database, Nutrients,
doi:10.3390/nu13082722Witkowska, Waśkiewicz, Zujko, Szcześniewska, Stepaniak et al., Are total and individual dietary lignans related to cardiovascular disease and its risk factors in postmenopausal women? A nationwide study, Nutrients,
doi:10.3390/nu10070865Wu, Liu, Wang, β-Sitosterol inhibits trimethylamine production by regulating the gut microbiota and attenuates atherosclerosis in ApoE-/-mice, Front Cardiovasc Med,
doi:10.3389/fcvm.2022.986905Wu, Pegan, Crich, Desrochers, Starling et al., Polyphenols as alternative treatments of COVID-19, Comput Struct Biotechnol J,
doi:10.1016/j.csbj.2021.09.022Wu, Wang, Li, Matairesinol exerts anti-inflammatory and antioxidant effects in sepsis-mediated brain injury by repressing the MAPK and NF-κB pathways through up-regulating AMPK, Aging (Albany NY,
doi:10.18632/aging.203649Yan, Chu, Yang, Sze, Lai et al., Characterization of the lipidomic profile of human coronavirus-infected cells: implications for lipid metabolism Remodeling upon coronavirus replication, Viruses,
doi:10.3390/v11010073Yanagisawa, He, Asai, Hellwig, Henle et al., The impacts of cholesterol, oxysterols, and cholesterol lowering dietary compounds on the immune system, Int J Mol Sci,
doi:10.3390/ijms232012236Yang, Mcdonald, Patel, Zhang, Umetani et al., Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands, J Biol Chem,
doi:10.1074/jbc.M603781200Yang, Yu, Li, Xu, Cohen et al., Disruption of cholesterol homeostasis by plant sterols, J Clin Invest,
doi:10.1172/JCI22186Yuan, Zhang, Shen, Jia, Xie, Phytosterols suppress phagocytosis and inhibit inflammatory mediators via ERK pathway on LPS-triggered inflammatory responses in RAW264.7 macrophages and the correlation with their structure. Foods,
doi:10.3390/foods8110582Zhang, Balasooriya, Sirisena, Ng, The effectiveness of dietary polyphenols in obesity management: a systematic review and meta-analysis of human clinical trials, Food Chem,
doi:10.1016/j.foodchem.2022.134668Zhang, Cheng, Wang, Liu, Ren et al., Secoisolariciresinol Diglucoside exerts anti-inflammatory and antiapoptotic effects through inhibiting the Akt/IκB/NF-κB pathway on human umbilical vein endothelial cells, Mediat Inflamm,
doi:10.1155/2020/3621261Zhuang, Zhong, Zhang, Chen, Huang et al., Exploring the potential mechanism of Shufeng Jiedu capsule for treating COVID-19 by comprehensive network pharmacological approaches and molecular docking validation, Comb Chem High Throughput Screen,
doi:10.1016/j.jff.2020.104146
