Oral intake of Kluyveromyces marxianus B0399 plus Lactobacillus rhamnosus CECT 30579 to mitigate symptoms in COVID-19 patients: A randomized open label clinical trial
Vicente Navarro-López, Adriana Hernández-Belmonte, Maria Isabel Pérez Soto, Maikel I Ayo-González, Guillermo Losa-Rodríguez, Esther Ros-Sánchez, Maravillas Martínez-Gabarrón, Pedro Sánchez-Pellicer, Juan Aguera-Santos, Eva Núñez-Delegido, Beatriz Ruzafa-Costas, José Antonio Picó-Monllor, Laura Navarro-Moratalla
Medicine in Microecology, doi:10.1016/j.medmic.2022.100061
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Medicine in Microecology
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References
Bourgonje, Abdulle, Timens, Hillebrands, Navis et al., Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19), J Pathol,
doi:10.1002/path.5471Cardinale, Capurso, Ianiro, Gasbarrini, Arcidiacono et al., Intestinal permeability changes with bacterial translocation as key events modulating systemic host immune response to SARS-CoV-2: A working hypothesis, Dig Liver Dis,
doi:10.1016/j.dld.2020.09.009Cecchini, Zanvit, Miclavez, Nobili, Halitosis Treatment Through the Administration of Antibiotic-Resistant Probiotic Lactic Yeast Kluyveromyces marxianus fragilis B0399 (K-B0399), Biomedical Journal of Scientific and Technical Research
Cristofori, Dargenio, Dargenio, Miniello, Barone et al., Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body, Front Immunol,
doi:10.3389/fimmu.2021.578386Ezechukwu, Diya, Egoh, Abiodun, Grace et al., Lung microbiota dysbiosis and the implications of SARS-CoV-2 infection in pregnancy, Ther Adv Infect Dis,
doi:10.1177/20499361211032453Foladori, Cutrupi, Segata, Manara, Pinto et al., SARS-CoV-2 from faeces to wastewater treatment: What do we know? A review, Sci Total Environ,
doi:10.1016/j.scitotenv.2020.140444Fonseca, Heinzle, Wittmann, Gombert, The yeast Kluyveromyces marxianus and its biotechnological potential, Appl Microbiol Biotechnol,
doi:10.1007/s00253-008-1458-6Gutierrez-Castrellon, Gandara-Marti, Abreu, Nieto-Rufino, Lopez-Orduna et al., Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial, Gut Microbes,
doi:10.1080/19490976.2021.2018899Jernberg, Lofmark, Edlund, Jansson, Long-term impacts of antibiotic exposure on the human intestinal microbiota, Microbiology (Reading,
doi:10.1099/mic.0.040618-0Kim, Guevarra, Kim, Kwon, Kim et al., Role of Probiotics in Human Gut Microbiome-Associated Diseases, J Microbiol Biotechnol,
doi:10.4014/jmb.1906.06064Kirtipal, Kumar, Dubey, Dwivedi, Gireesh Babu et al., Understanding on the possible routes for SARS CoV-2 invasion via ACE2 in the host linked with multiple organs damage, Infect Genet Evol,
doi:10.1016/j.meegid.2022.105254Labandeira-Garcia, Labandeira, Valenzuela, Pedrosa, Quijano et al., Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment, Biomedicines,
doi:10.3390/biomedicines10020502Leal-Martinez, Abarca-Bernal, Garcia-Perez, Gonzalez-Tolosa, Cruz-Cazares et al., Effect of a Nutritional Support System to Increase Survival and Reduce Mortality in Patients with COVID-19 in Stage III and Comorbidities: A Blinded Randomized Controlled Clinical Trial, Int J Environ Res Public Health,
doi:10.3390/ijerph19031172Li, He, Zhu, Lu, Role of gut microbiota on intestinal barrier function in acute pancreatitis, World J Gastroenterol,
doi:10.3748/wjg.v26.i18.2187Li, Pei, Chen, Song, Zhang et al., Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (COVID-19), medRxiv,
doi:10.1101/2020.02.14.20023127Lisotti, Mazzella, Su2037 effects of a fermented milk containing Kluyveromyces marxianus B0399 and Bifidobacterium Lactis BB12 in patients with irritable bowel syndrome: a new effective agent, Gastroenterology
Maccaferri, Candela, Turroni, Centanni, Severgnini et al., IBS-associated phylogenetic unbalances of the intestinal microbiota are not reverted by probiotic supplementation, Gut Microbes,
doi:10.4161/gmic.21009Maccaferri, Klinder, Brigidi, Cavina, Costabile, Potential probiotic Kluyveromyces marxianus B0399 modulates the immune response in Caco-2 cells and peripheral blood mononuclear cells and impacts the human gut microbiota in an in vitro colonic model system, Appl Environ Microbiol,
doi:10.1128/AEM.06385-11Meng, Zhang, Cao, Yu, Fang et al., Gut dysbacteriosis and intestinal disease: mechanism and treatment, J Appl Microbiol,
doi:10.1111/jam.14661Page, Kell, Pretorius, The Role of Lipopolysaccharide-Induced Cell Signalling in Chronic Inflammation, Chronic Stress,
doi:10.1177/24705470221076390Quarella, Lovrovich, Scalabrin, Campedelli, Backovic et al., Draft Genome Sequence of the Probiotic Yeast Kluyveromyces marxianus fragilis B0399, Genome Announc,
doi:10.1128/genomeA.00923-16Rodriguez, Bifano, Roca Goma, Plasencia, Torralba et al., Effect and Tolerability of a Nutritional Supplement Based on a Synergistic Combination of beta-Glucans and Selenium-and Zinc-Enriched Saccharomyces cerevisiae (ABB C1((R))) in Volunteers Receiving the Influenza or the COVID-19 Vaccine: A Randomized, Double-Blind, Placebo-Controlled Study, Nutrients,
doi:10.3390/nu13124347Sanders, Merenstein, Reid, Gibson, Rastall, Probiotics and prebiotics in intestinal health and disease: from biology to the clinic, Nat Rev Gastroenterol Hepatol,
doi:10.1038/s41575-019-0173-3Singh, Sharma, Lee, Yadav, SARS-CoV-2: Recent Variants and Clinical Efficacy of Antibody-Based Therapy, Front Cell Infect Microbiol,
doi:10.3389/fcimb.2022.839170Theodorakopoulou, Alexandrou, Boutou, Ferro, Ortiz et al., Renin-angiotensin system blockers during the COVID-19 pandemic: an update for patients with hypertension and chronic kidney disease, Clin Kidney J,
doi:10.1093/ckj/sfab272Willers, Viemann, Role of the gut microbiota in airway immunity and host defense against respiratory infections, Biol Chem,
doi:10.1515/hsz-2021-0281Xu, Li, Zhu, Liang, Fang et al., Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding, Nat Med,
doi:10.1038/s41591-020-0817-4Zhang, Wang, Chen, Interactions between Intestinal Microflora/Probiotics and the Immune System, Biomed Res Int,
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