Antioxidant Effect of a Probiotic Product on a Model of Oxidative Stress Induced by High-Intensity and Duration Physical Exercise

Maravillas Sánchez Macarro, Vicente Ávila-Gandía, Silvia Pérez-Piñero, Fernando Cánovas, Ana María García-Muñoz, María Salud Abellán-Ruiz, Desirée Victoria-Montesinos, Antonio J Luque-Rubia, Eric Climent, Salvador Genovés, Daniel Ramon, Empar Chenoll, Francisco Javier López-Román, Maravillas Sánchez Macarro, Vicente Ávila-Gandía, Silvia Pérez-Piñero, Fernando Cánovas, Ana María García-Muñoz, María Salud Abellán-Ruiz, Desirée Victoria-Montesinos, Antonio J Luque-Rubia, Eric Climent, Salvador Genovés, Daniel Ramon, Empar Chenoll, Francisco Javier López-Román

Abstract

This randomized double-blind and controlled single-center clinical trial was designed to evaluate the effect of a 6-week intake of a probiotic product (1 capsule/day) vs. a placebo on an oxidative stress model of physical exercise (high intensity and duration) in male cyclists (probiotic group, n = 22; placebo, n = 21). This probiotic included three lyophilized strains (Bifidobacterium longum CECT 7347, Lactobacillus casei CECT 9104, and Lactobacillus rhamnosus CECT 8361). Study variables were urinary isoprostane, serum malondialdehyde (MDA), serum oxidized low-density lipoprotein (Ox-LDL), urinary 8-hydroxy-2'-deoxiguanosine (8-OHdG), serum protein carbonyl, serum glutathione peroxidase (GPx), and serum superoxide dismutase (SOD). At 6 weeks, as compared with baseline, significant differences in 8-OHdG (Δ mean difference -10.9 (95% CI -14.5 to -7.3); p < 0.001), MDA (Δ mean difference -207.6 (95% CI -349.1 to -66.1; p < 0.05), and Ox-LDL (Δ mean difference -122.5 (95% CI -240 to -4.5); p < 0.05) were found in the probiotic group only. Serum GPx did not increase in the probiotic group, whereas the mean difference was significant in the placebo group (477.8 (95% CI 112.5 to 843.2); p < 0.05). These findings suggest an antioxidant effect of this probiotic on underlying interacting oxidative stress mechanisms and their modulation in healthy subjects. The study was registered in ClinicalTrials.gov (NCT03798821).

Keywords: antioxidative enzymes; male cyclists; oxidative stress; oxidative stress biomarkers; physical exercise; probiotics.

Conflict of interest statement

Eric Climent, Salvador Genovés, Daniel Ramon and Empar Chenoll are employees of ADM-Biopolis. All other authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of the study population.
Figure 2
Figure 2
Local contributions to beta diversity (LCBD) analysis at family level (right) and genus level (left) from taxonomic identification of the samples sequenced (42 samples in the placebo group and 44 samples in the probiotic group; T1: before test #1, T2: at 6 weeks before test #2).
Figure 3
Figure 3
Richness, Simpson diversity index, and Shannon diversity index (from left to right) in the placebo and probiotic group at baseline (T1) and at 6 weeks (end of study) (T2).
Figure 4
Figure 4
Differences between the placebo and probiotic groups at the end of the study (6 weeks) at the level of families (A) and genera (B).

References

    1. Pizzino G., Irrera N., Cucinotta M., Pallio G., Mannino F., Arcoraci V., Squadrito F., Altavilla D., Bitto A. Oxidative stress: Harms and benefits for human health. Oxid. Med. Cell Longev. 2017;2017:8416763. doi: 10.1155/2017/8416763.
    1. Schieber M., Chandel N.S. ROS function in redox signaling and oxidative stress. Curr. Biol. 2014;24:R453–R462. doi: 10.1016/j.cub.2014.03.034.
    1. Ray P.D., Huang B.-W., Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012;24:981–990. doi: 10.1016/j.cellsig.2012.01.008.
    1. Mittal M., Siddiqui M.R., Tran K., Reddy S.P., Malik A.B. Reactive oxygen species in inflammation and tissue injury. Antioxid. Redox. Signal. 2014;20:1126–1167. doi: 10.1089/ars.2012.5149.
    1. Simpson D.S.A., Oliver P.L. ROS generation in microglia: Understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants. 2020;9:743. doi: 10.3390/antiox9080743.
    1. Dubois-Deruy E., Peugnet V., Turkieh A., Pinet F. Oxidative stress in cardiovascular diseases. Antioxidants. 2020;9:864. doi: 10.3390/antiox9090864.
    1. Yaribeygi H., Sathyapalan T., Atkin S.L., Sahebkar A. Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus. [(accessed on 27 January 2021)]; Available online:
    1. Romano A.D., Serviddio G., de Matthaeis A., Bellanti F., Vendemiale G. Oxidative stress and aging. J. Nephrol. 2010;23(Suppl. S15):S29–S36.
    1. Vasquez E.C., Pereira T.M.C., Campos-Toimil M., Baldo M.P., Peotta V.A. Gut microbiota, diet, and chronic diseases: The role played by oxidative stress. Oxid. Med. Cell Longev. 2019;2019 doi: 10.1155/2019/7092032.
    1. Jones R.M., Mercante J.W., Neish A.S. Reactive oxygen production induced by the gut microbiota: Pharmacotherapeutic implications. Curr. Med. Chem. 2012;19:1519–1529. doi: 10.2174/092986712799828283.
    1. Neish A.S. Microbes in gastrointestinal health and disease. Gastroenterology. 2009;136:65–80. doi: 10.1053/j.gastro.2008.10.080.
    1. Chung H., Kasper D.L. Microbiota-stimulated immune mechanisms to maintain gut homeostasis. Curr. Opin. Immunol. 2010;22:455–460. doi: 10.1016/j.coi.2010.06.008.
    1. Ismail A.S., Hooper L.V. Epithelial cells and their neighbors. IV. bacterial contributions to intestinal epithelial barrier integrity. Am. J. Physiol. Gastrointest. Liver Physiol. 2005;289:G779–G784. doi: 10.1152/ajpgi.00203.2005.
    1. Prado C., Michels M., Ávila P., Burger H., Milioli M.V.M., Dal-Pizzol F. The protective effects of fecal microbiota transplantation in an experimental model of necrotizing enterocolitis. J. Pediatr. Surg. 2019;54:1578–1583. doi: 10.1016/j.jpedsurg.2018.10.045.
    1. Wang Y., Wu Y., Wang Y., Xu H., Mei X., Yu D., Wang Y., Li W. Antioxidant properties of probiotic bacteria. Nutrients. 2017;9:521. doi: 10.3390/nu9050521.
    1. He F., Li J., Liu Z., Chuang C.-C., Yang W., Zuo L. Redox mechanism of reactive oxygen species in exercise. Front. Physiol. 2016;7 doi: 10.3389/fphys.2016.00486.
    1. Radak Z., Zhao Z., Koltai E., Ohno H., Atalay M. Oxygen consumption and usage during physical exercise: The balance between oxidative stress and ROS-dependent adaptive signaling. Antioxid. Redox. Signal. 2013;18:1208–1246. doi: 10.1089/ars.2011.4498.
    1. Kawamura T., Muraoka I. Exercise-induced oxidative stress and the effects of antioxidant intake from a physiological viewpoint. Antioxidants. 2018;7:119. doi: 10.3390/antiox7090119.
    1. Pingitore A., Lima G.P.P., Mastorci F., Quinones A., Iervasi G., Vassalle C. Exercise and oxidative stress: Potential effects of antioxidant dietary strategies in sports. Nutrition. 2015;31:916–922. doi: 10.1016/j.nut.2015.02.005.
    1. Powers S.K., DeRuisseau K.C., Quindry J., Hamilton K.L. Dietary antioxidants and exercise. J. Sports Sci. 2004;22:81–94. doi: 10.1080/0264041031000140563.
    1. Genomic Sequence and Pre-Clinical Safety Assessment of Bifidobacterium Longum CECT 7347, a Probiotic Able to Reduce the Toxicity and Inflammatory Potential of Gliadin-Derived Peptides|Abstract. [(accessed on 27 January 2021)]; Available online: .
    1. Klindworth A., Pruesse E., Schweer T., Peplies J., Quast C., Horn M., Glöckner F.O. Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res. 2013;41:e1. doi: 10.1093/nar/gks808.
    1. Krotkiewski M., Brzezinska Z. Lipid peroxides production after strenuous exercise and in relation to muscle morphology and capillarization. Muscle Nerve. 1996;19:1530. doi: 10.1002/(SICI)1097-4598(199612)19:12<1530::AID-MUS2>;2-B.
    1. Powers S.K., Jackson M.J. Exercise-induced oxidative stress: Cellular mechanisms and impact on muscle force production. Physiol. Rev. 2008;88:1243–1276. doi: 10.1152/physrev.00031.2007.
    1. Criswell D., Powers S., Dodd S., Lawler J., Edwards W., Renshler K., Grinton S. High intensity training-induced changes in skeletal muscle antioxidant enzyme activity. Med. Sci. Sports Exerc. 1993;25:1135–1140. doi: 10.1249/00005768-199310000-00009.
    1. Hammeren J., Powers S., Criswell D., Martin A., Lowenthal D., Pollock M. Exercise training-induced alterations in skeletal muscle oxidative and antioxidant enzyme activity in senescent rats. Int. J. Sports Med. 1992;13:412–416. doi: 10.1055/s-2007-1021290.
    1. Theofilidis G., Bogdanis G.C., Koutedakis Y., Karatzaferi C. Monitoring exercise-induced muscle fatigue and adaptations: Making sense of popular or emerging indices and biomarkers. Sports. 2018;6:153. doi: 10.3390/sports6040153.
    1. De Salazar L., Torregrosa-García A., Luque-Rubia A.J., Ávila-Gandía V., Domingo J.C., López-Román F.J. Oxidative stress in endurance cycling is reduced dose-dependently after one month of re-esterified DHA supplementation. Antioxidants. 2020;9:1145. doi: 10.3390/antiox9111145.
    1. Torregrosa-García A., Ávila-Gandía V., Luque-Rubia A.J., Abellán-Ruiz M.S., Querol-Calderón M., López-Román F.J. Pomegranate extract improves maximal performance of trained cyclists after an exhausting endurance trial: A randomised controlled trial. Nutrients. 2019;11:721. doi: 10.3390/nu11040721.
    1. Martínez-Sánchez A., Alacid F., Rubio-Arias J.A., Fernández-Lobato B., Ramos-Campo D.J., Aguayo E. Consumption of watermelon juice enriched in L-citrulline and pomegranate ellagitannins enhanced metabolism during physical exercise. J. Agric. Food Chem. 2017;65:4395–4404. doi: 10.1021/acs.jafc.7b00586.
    1. López-Román F.J., Ávila-Gandía V., Contreras-Fernández C.J., Luque-Rubia A.J., Villegas-García J.A. Effect of docosahexaenoic acid supplementation on differences of endurance exercise performance in competitive and non-competitive male cyclists. Gazz. Med. Ital. Arch. Sci. Med. 2019;178:411–416. doi: 10.23736/S0393-3660.18.03860-3.
    1. Ramos-Campo D.J., Ávila-Gandía V., López-Román F.J., Miñarro J., Contreras C., Soto-Méndez F., Domingo Pedrol J.C., Luque-Rubia A.J. Supplementation of re-esterified docosahexaenoic and eicosapentaenoic acids reduce inflammatory and muscle damage markers after exercise in endurance athletes: A randomized, controlled crossover trial. Nutrients. 2020;12:719. doi: 10.3390/nu12030719.
    1. Mishra V., Shah C., Mokashe N., Chavan R., Yadav H., Prajapati J. Probiotics as potential antioxidants: A systematic review. J. Agric. Food Chem. 2015;63:3615–3626. doi: 10.1021/jf506326t.
    1. Michalickova D., Kotur-Stevuljevic J., Miljkovic M., Dikic N., Kostic-Vucicevic M., Andjelkovic M., Koricanac V., Djordjevic B. Effects of probiotic supplementation on selected parameters of blood prooxidant-antioxidant balance in elite athletes: A double-blind randomized placebo-controlled study. J. Hum. Kinet. 2018;64:111–122. doi: 10.1515/hukin-2017-0203.
    1. Martarelli D., Verdenelli M.C., Scuri S., Cocchioni M., Silvi S., Cecchini C., Pompei P. Effect of a probiotic intake on oxidant and antioxidant parameters in plasma of athletes during intense exercise training. Curr. Microbiol. 2011;62:1689–1696. doi: 10.1007/s00284-011-9915-3.
    1. Lamprecht M., Bogner S., Schippinger G., Steinbauer K., Fankhauser F., Hallstroem S., Schuetz B., Greilberger J.F. Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial. J. Int. Soc. Sports Nutr. 2012;9:45. doi: 10.1186/1550-2783-9-45.
    1. Välimäki I.A., Vuorimaa T., Ahotupa M., Kekkonen R., Korpela R., Vasankari T. Decreased training volume and increased carbohydrate intake increases oxidized LDL levels. Int. J. Sports Med. 2012;33:291–296. doi: 10.1055/s-0031-1291223.
    1. Ardeshirlarijani E., Tabatabaei-Malazy O., Mohseni S., Qorbani M., Larijani B., Baradar Jalili R. Effect of probiotics supplementation on glucose and oxidative stress in type 2 diabetes mellitus: A meta-analysis of randomized trials. Daru. 2019;27:827–837. doi: 10.1007/s40199-019-00302-2.
    1. Valko M., Izakovic M., Mazur M., Rhodes C.J., Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol. Cell Biochem. 2004;266:37–56. doi: 10.1023/B:MCBI.0000049134.69131.89.
    1. Escamilla J., Lane M.A., Maitin V. Cell-free supernatants from probiotic lactobacillus casei and lactobacillus rhamnosus GG decrease colon cancer cell invasion in vitro. Nutr. Cancer. 2012;64:871–878. doi: 10.1080/01635581.2012.700758.
    1. Tiptiri-Kourpeti A., Spyridopoulou K., Santarmaki V., Aindelis G., Tompoulidou E., Lamprianidou E.E., Saxami G., Ypsilantis P., Lampri E.S., Simopoulos C., et al. Lactobacillus casei exerts anti-proliferative effects accompanied by apoptotic cell death and up-regulation of TRAIL in colon carcinoma cells. PLoS ONE. 2016;11:e0147960. doi: 10.1371/journal.pone.0147960.
    1. Jacouton E., Mach N., Cadiou J., Lapaque N., Clément K., Doré J., van Hylckama Vlieg J.E.T., Smokvina T., Blottière H.M. Lactobacillus rhamnosus CNCMI-4317 modulates fiaf/angptl4 in intestinal epithelial cells and circulating level in mice. PLoS ONE. 2015;10:e0138880. doi: 10.1371/journal.pone.0138880.
    1. Black C.N., Bot M., Scheffer P.G., Cuijpers P., Penninx B.W.J.H. Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology. 2015;51:164–175. doi: 10.1016/j.psyneuen.2014.09.025.
    1. Collins A.R., Cadet J., Möller L., Poulsen H.E., Viña J. Are we sure we know how to measure 8-Oxo-7,8-dihydroguanine in DNA from human cells? Arch. Biochem. Biophys. 2004;423:57–65. doi: 10.1016/j.abb.2003.12.022.
    1. Dizdaroglu M., Jaruga P., Birincioglu M., Rodriguez H. Free radical-induced damage to DNA: Mechanisms and measurement. Free Radic. Biol. Med. 2002;32:1102–1115. doi: 10.1016/S0891-5849(02)00826-2.
    1. Mikhed Y., Görlach A., Knaus U.G., Daiber A. Redox regulation of genome stability by effects on gene expression, epigenetic pathways and DNA damage/repair. Redox. Biol. 2015;5:275–289. doi: 10.1016/j.redox.2015.05.008.
    1. Wu Q., Ni X. ROS-mediated DNA methylation pattern alterations in carcinogenesis. Curr. Drug Targets. 2015;16:13–19. doi: 10.2174/1389450116666150113121054.
    1. Samuel B.S., Gordon J.I. A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism. Proc. Natl. Acad. Sci. USA. 2006;103:10011–10016. doi: 10.1073/pnas.0602187103.
    1. Samuel B.S., Hansen E.E., Manchester J.K., Coutinho P.M., Henrissat B., Fulton R., Latreille P., Kim K., Wilson R.K., Gordon J.I. Genomic and metabolic adaptations of methanobrevibacter smithii to the human gut. Proc. Natl. Acad. Sci. USA. 2007;104:10643–10648. doi: 10.1073/pnas.0704189104.
    1. Bianchi F., Larsen N., de Mello Tieghi T., Adorno M.A.T., Kot W., Saad S.M.I., Jespersen L., Sivieri K. Modulation of gut microbiota from obese individuals by in vitro fermentation of citrus pectin in combination with bifidobacterium longum BB-46. Appl. Microbiol. Biotechnol. 2018;102:8827–8840. doi: 10.1007/s00253-018-9234-8.
    1. Yang C., Deng Q., Xu J., Wang X., Hu C., Tang H., Huang F. Sinapic acid and resveratrol alleviate oxidative stress with modulation of gut microbiota in high-fat diet-fed rats. Food Res. Int. 2019;116:1202–1211. doi: 10.1016/j.foodres.2018.10.003.
    1. Eren A.M., Sogin M.L., Morrison H.G., Vineis J.H., Fisher J.C., Newton R.J., McLellan S.L. A single genus in the gut microbiome reflects host preference and specificity. ISME J. 2015;9:90–100. doi: 10.1038/ismej.2014.97.
    1. Allen J.M., Mailing L.J., Niemiro G.M., Moore R., Cook M.D., White B.A., Holscher H.D., Woods J.A. Exercise alters gut microbiota composition and function in lean and obese humans. Med. Sci. Sports Exerc. 2018;50:747–757. doi: 10.1249/MSS.0000000000001495.
    1. Lebas M., Garault P., Carrillo D., Codoñer F.M., Derrien M. Metabolic response of Faecalibacterium prausnitzii to cell-free supernatants from lactic acid bacteria. Microorganisms. 2020;8:1528. doi: 10.3390/microorganisms8101528.
    1. Edamatsu T., Fujieda A., Itoh Y. Phenyl sulfate, indoxyl sulfate and p-cresyl sulfate decrease glutathione level to render cells vulnerable to oxidative stress in renal tubular cells. PLoS ONE. 2018;13:e0193342. doi: 10.1371/journal.pone.0193342.
    1. Asai H., Hirata J., Hirano A., Hirai K., Seki S., Watanabe-Akanuma M. Activation of aryl hydrocarbon receptor mediates suppression of hypoxia-inducible factor-dependent erythropoietin expression by indoxyl sulfate. Am. J. Physiol. Cell Physiol. 2016;310:C142–C150. doi: 10.1152/ajpcell.00172.2015.
    1. Eleftheriadis T., Pissas G., Antoniadi G., Liakopoulos V., Stefanidis I. Kynurenine, by activating aryl hydrocarbon receptor, decreases erythropoietin and increases hepcidin production in HepG2 cells: A new mechanism for anemia of inflammation. Exp. Hematol. 2016;44:60–67. doi: 10.1016/j.exphem.2015.08.010.
    1. Hu S., Kuwabara R., de Haan B.J., Smink A.M., de Vos P. Acetate and butyrate improve β-cell metabolism and mitochondrial respiration under oxidative stress. Int. J. Mol. Sci. 2020;21:1542. doi: 10.3390/ijms21041542.
    1. Yardeni T., Tanes C.E., Bittinger K., Mattei L.M., Schaefer P.M., Singh L.N., Wu G.D., Murdock D.G., Wallace D.C. Host mitochondria influence gut microbiome diversity: A role for ROS. Sci. Signal. 2019;12:588. doi: 10.1126/scisignal.aaw3159.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever