Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves Outcomes of Mild COVID-19

DOI record: { "DOI": "10.3390/nu15030488", "ISSN": [ "2072-6643" ], "URL": "http://dx.doi.org/10.3390/nu15030488", "abstract": "<jats:p>Spore-based Bacillus probiotic treatment improves intestinal health. The intestinal microbiota influences both the innate and adaptive immune responses. As such, the influence of ongoing spore-based probiotic treatment (five probiotic strains of Bacillus) on the clinical outcomes of mild COVID-19 was evaluated in this retrospective, observational study. Demographics, medical history, probiotic use, and COVID-19 symptom information were collected. The study included 120 patients with a PCR-confirmed SARS-CoV-2 infection and mild COVID-19 symptoms. The probiotic group (n = 60) comprised patients with ongoing probiotic treatment (≥1 month); the control group comprised patients not taking probiotics (n = 60). The primary outcome was time to symptom resolution; secondary outcomes included time to fever resolution and presence of digestive symptoms. The probiotic group had a significantly shorter time to symptom resolution (mean (95% confidence interval) days: control group, 8.48 (6.56, 10.05); probiotic group, 6.63 (5.56; 6.63); p = 0.003) and resolution of fever (control group, 2.67 (1.58, 3.61); probiotic group, 1.48 (1.21, 2.03); p &lt; 0.001). More patients in the probiotic group (n = 53) than in the control group (n = 34) did not have digestive symptoms (p &lt; 0.001). Among adults with mild COVID-19, participants receiving ongoing probiotic treatment had a shorter clinical course, and fewer had digestive symptoms compared with those not taking probiotics.</jats:p>", "alternative-id": [ "nu15030488" ], "author": [ { "ORCID": "http://orcid.org/0000-0002-6327-6608", "affiliation": [], "authenticated-orcid": false, "family": "Catinean", "given": "Adrian", "sequence": "first" }, { "affiliation": [], "family": "Sida", "given": "Anamaria", "sequence": "additional" }, { "affiliation": [], "family": "Silvestru", "given": "Celina", "sequence": "additional" }, { "affiliation": [], "family": "Balan", "given": "Gheorghe G.", "sequence": "additional" } ], "container-title": "Nutrients", "container-title-short": "Nutrients", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2023, 1, 18 ] ], "date-time": "2023-01-18T07:31:11Z", "timestamp": 1674027071000 }, "deposited": { "date-parts": [ [ 2023, 1, 18 ] ], "date-time": "2023-01-18T07:56:49Z", "timestamp": 1674028609000 }, "indexed": { "date-parts": [ [ 2023, 1, 19 ] ], "date-time": "2023-01-19T06:09:29Z", "timestamp": 1674108569894 }, "is-referenced-by-count": 0, "issue": "3", "issued": { "date-parts": [ [ 2023, 1, 17 ] ] }, "journal-issue": { "issue": "3", "published-online": { "date-parts": [ [ 2023, 2 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 1, 17 ] ], "date-time": "2023-01-17T00:00:00Z", "timestamp": 1673913600000 } } ], "link": [ { "URL": "https://www.mdpi.com/2072-6643/15/3/488/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "488", "prefix": "10.3390", "published": { "date-parts": [ [ 2023, 1, 17 ] ] }, "published-online": { "date-parts": [ [ 2023, 1, 17 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1053/j.gastro.2020.05.048", "article-title": "Alterations in Gut Microbiota of Patients with COVID-19 during Time of Hospitalization", "author": "Zuo", "doi-asserted-by": "crossref", "first-page": "944", "journal-title": "Gastroenterology", "key": "ref_1", "volume": "159", "year": "2020" }, { "key": "ref_2", "unstructured": "WHO (2023, January 16). Coronavirus (COVID-19) Dashboard. Available online: https://covid19.who.int/#:~:text=Globally%2C%20as%20of%204%3A54pm,vaccine%20doses%20have%20been%20administered." }, { "DOI": "10.1136/bmj.j5145", "article-title": "The role of the gut microbiome in systemic inflammatory disease", "author": "Clemente", "doi-asserted-by": "crossref", "first-page": "j5145", "journal-title": "BMJ", "key": "ref_3", "volume": "360", "year": "2018" }, { "DOI": "10.1038/s41577-022-00727-y", "article-title": "The impact of the gut microbiome on extra-intestinal autoimmune diseases", "author": "Miyauchi", "doi-asserted-by": "crossref", "first-page": "9", "journal-title": "Nat. Rev. Immunol.", "key": "ref_4", "volume": "23", "year": "2023" }, { "DOI": "10.4161/gmic.19320", "article-title": "The role of gut microbiota in immune homeostasis and autoimmunity", "author": "Wu", "doi-asserted-by": "crossref", "first-page": "4", "journal-title": "Gut Microbes", "key": "ref_5", "volume": "3", "year": "2012" }, { "DOI": "10.1186/s12866-021-02192-4", "doi-asserted-by": "crossref", "key": "ref_6", "unstructured": "Han, S.K., Shin, Y.J., Lee, D.Y., Kim, K.M., Yang, S.J., Kim, D.S., Choi, J.W., Lee, S., and Kim, D.H. (2021). Lactobacillus rhamnosus HDB1258 modulates gut microbiota-mediated immune response in mice with or without lipopolysaccharide-induced systemic inflammation. BMC Microbiol., 21." }, { "DOI": "10.3389/fimmu.2021.750969", "article-title": "SARS-CoV-2 Nsp5 Activates NF-kappaB Pathway by Upregulating SUMOylation of MAVS", "author": "Li", "doi-asserted-by": "crossref", "first-page": "750969", "journal-title": "Front. Immunol.", "key": "ref_7", "volume": "12", "year": "2021" }, { "DOI": "10.1111/lam.13334", "article-title": "Probiotics and COVID-19: Is there any link?", "author": "Akour", "doi-asserted-by": "crossref", "first-page": "229", "journal-title": "Lett. Appl. Microbiol.", "key": "ref_8", "volume": "71", "year": "2020" }, { "DOI": "10.1128/CMR.00228-20", "article-title": "Tools and Techniques for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/COVID-19 Detection", "author": "LeBlanc", "doi-asserted-by": "crossref", "first-page": "e00228-20", "journal-title": "Clin. Microbiol. Rev.", "key": "ref_9", "volume": "34", "year": "2021" }, { "DOI": "10.1053/j.gastro.2021.10.040", "article-title": "Potential long coronavirus disease 2019 gastrointestinal symptoms 6 months after coronavirus infection are associated with mental health symptoms", "author": "Blackett", "doi-asserted-by": "crossref", "first-page": "648", "journal-title": "Gastroenterology", "key": "ref_10", "volume": "162", "year": "2022" }, { "DOI": "10.14309/ajg.0000000000000620", "article-title": "Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study", "author": "Pan", "doi-asserted-by": "crossref", "first-page": "766", "journal-title": "Am. J. Gastroenterol.", "key": "ref_11", "volume": "115", "year": "2020" }, { "DOI": "10.3390/nu14020274", "doi-asserted-by": "crossref", "key": "ref_12", "unstructured": "Nguyen, Q.V., Chong, L.C., Hor, Y.Y., Lew, L.C., Rather, I.A., and Choi, S.B. (2022). Role of Probiotics in the Management of COVID-19: A Computational Perspective. Nutrients, 14." }, { "DOI": "10.1080/10408398.2022.2143476", "doi-asserted-by": "crossref", "key": "ref_13", "unstructured": "Rossini, V., Tolosa-Enguis, V., Frances-Cuesta, C., and Sanz, Y. (2022). Gut microbiome and anti-viral immunity in COVID-19. Crit. Rev. Food Sci. Nutr., 1–16." }, { "DOI": "10.1016/j.arcmed.2021.03.002", "article-title": "Probiotics in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects", "author": "Kurian", "doi-asserted-by": "crossref", "first-page": "582", "journal-title": "Arch. Med. Res.", "key": "ref_14", "volume": "52", "year": "2021" }, { "DOI": "10.2146/ajhp090168", "article-title": "Probiotics", "author": "Williams", "doi-asserted-by": "crossref", "first-page": "449", "journal-title": "Am. J. Health Syst. Pharm.", "key": "ref_15", "volume": "67", "year": "2010" }, { "DOI": "10.3390/nu13124347", "article-title": "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", "author": "Rodriguez", "doi-asserted-by": "crossref", "first-page": "4347", "journal-title": "Nutrients", "key": "ref_16", "volume": "13", "year": "2021" }, { "DOI": "10.3390/ijerph19031172", "doi-asserted-by": "crossref", "key": "ref_17", "unstructured": "Leal-Martinez, F., Abarca-Bernal, L., Garcia-Perez, A., Gonzalez-Tolosa, D., Cruz-Cazares, G., Montell-Garcia, M., and Ibarra, A. (2022). 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, 19." }, { "DOI": "10.1128/spectrum.01682-22", "article-title": "Randomized, Double-Blind, Placebo-Controlled Trial of a Throat Spray with Selected Lactobacilli in COVID-19 Outpatients", "author": "Cauwenberghs", "doi-asserted-by": "crossref", "first-page": "e0168222", "journal-title": "Microbiol. Spectr.", "key": "ref_18", "volume": "10", "year": "2022" }, { "DOI": "10.3390/microorganisms8071028", "doi-asserted-by": "crossref", "key": "ref_19", "unstructured": "Marzorati, M., Abbeele, P.V.D., Bubeck, S.S., Bayne, T., Krishnan, K., Young, A., Mehta, D., and DeSouza, A. (2020). Bacillus subtilis HU58 and Bacillus coagulans SC208 Probiotics Reduced the Effects of Antibiotic-Induced Gut Microbiome Dysbiosis in an M-SHIME® Model. Microorganisms, 8." }, { "article-title": "The effect of Probiotic Bacillus Subtilis HU58 on Immune Function in Healthy Human", "author": "Dound", "first-page": "15", "journal-title": "Indian Pract.", "key": "ref_20", "volume": "70", "year": "2019" }, { "DOI": "10.4291/wjgp.v8.i3.117", "article-title": "Oral spore-based probiotic supplementation was associated with reduced incidence of post-prandial dietary endotoxin, triglycerides, and disease risk biomarkers", "author": "McFarlin", "doi-asserted-by": "crossref", "first-page": "117", "journal-title": "World J. Gastrointest Pathophysiol.", "key": "ref_21", "volume": "8", "year": "2017" }, { "DOI": "10.2217/fmb-2022-0066", "article-title": "Effects of combined prebiotic, probiotic, IgG and amino acid supplementation on the gut microbiome of patients with inflammatory bowel disease", "author": "Marzorati", "doi-asserted-by": "crossref", "first-page": "1307", "journal-title": "Future Microbiol.", "key": "ref_22", "volume": "17", "year": "2022" }, { "DOI": "10.1016/j.foodres.2021.110676", "article-title": "Treatment with a spore-based probiotic containing five strains of Bacillus induced changes in the metabolic activity and community composition of the gut microbiota in a SHIME(R) model of the human gastrointestinal system", "author": "Marzorati", "doi-asserted-by": "crossref", "first-page": "110676", "journal-title": "Food Res. Int.", "key": "ref_23", "volume": "149", "year": "2021" }, { "DOI": "10.1186/1471-230X-9-85", "doi-asserted-by": "crossref", "key": "ref_24", "unstructured": "Kalman, D.S., Schwartz, H.I., Alvarez, P., Feldman, S., Pezzullo, J.C., and Krieger, D.R. (2009). A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms. BMC Gastroenterol., 9." }, { "DOI": "10.1007/s10096-020-04138-6", "article-title": "COVID-19: Angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection", "author": "Beyerstedt", "doi-asserted-by": "crossref", "first-page": "905", "journal-title": "Eur. J. Clin. Microbiol. Infect. Dis.", "key": "ref_25", "volume": "40", "year": "2021" }, { "DOI": "10.1002/path.1570", "article-title": "Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis", "author": "Hamming", "doi-asserted-by": "crossref", "first-page": "631", "journal-title": "J. Pathol.", "key": "ref_26", "volume": "203", "year": "2004" }, { "DOI": "10.3390/molecules27175405", "doi-asserted-by": "crossref", "key": "ref_27", "unstructured": "Tanikawa, T., Kiba, Y., Yu, J., Hsu, K., Chen, S., Ishii, A., Yokogawa, T., Suzuki, R., Inoue, Y., and Kitamura, M. (2022). Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2. Molecules, 27." }, { "DOI": "10.1016/j.bbrc.2021.07.034", "article-title": "Natto extract, a Japanese fermented soybean food, directly inhibits viral infections including SARS-CoV-2 in vitro", "author": "Oba", "doi-asserted-by": "crossref", "first-page": "21", "journal-title": "Biochem. Biophys. Res. Commun.", "key": "ref_28", "volume": "570", "year": "2021" }, { "DOI": "10.1001/jama.2020.12839", "article-title": "Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review", "author": "Wiersinga", "doi-asserted-by": "crossref", "first-page": "782", "journal-title": "JAMA", "key": "ref_29", "volume": "324", "year": "2020" }, { "DOI": "10.1016/S2468-1253(20)30126-6", "article-title": "Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: A systematic review and meta-analysis", "author": "Mao", "doi-asserted-by": "crossref", "first-page": "667", "journal-title": "Lancet Gastroenterol. Hepatol.", "key": "ref_30", "volume": "5", "year": "2020" }, { "DOI": "10.1128/JVI.01396-21", "article-title": "Direct Activation of Endothelial Cells by SARS-CoV-2 Nucleocapsid Protein Is Blocked by Simvastatin", "author": "Qian", "doi-asserted-by": "crossref", "first-page": "e0139621", "journal-title": "J. Virol.", "key": "ref_31", "volume": "95", "year": "2021" }, { "DOI": "10.3390/nu12123607", "doi-asserted-by": "crossref", "key": "ref_32", "unstructured": "Catinean, A., Neag, M.A., Krishnan, K., Muntean, D.M., Bocsan, C.I., Pop, R.M., Mitre, A.O., Melincovici, C.S., and Buzoianu, A.D. (2020). Probiotic Bacillus Spores Together with Amino Acids and Immunoglobulins Exert Protective Effects on a Rat Model of Ulcerative Colitis. Nutrients, 12." }, { "DOI": "10.1007/978-3-319-92336-9", "doi-asserted-by": "crossref", "key": "ref_33", "unstructured": "El-Radhi, A.S. (2019). Clinical Manual of Fever in Children, Springer." }, { "DOI": "10.12998/wjcc.v9.i2.296", "article-title": "Effect of a fever in viral infections—The ‘Goldilocks’ phenomenon?", "author": "Belon", "doi-asserted-by": "crossref", "first-page": "296", "journal-title": "World J. Clin. Cases", "key": "ref_34", "volume": "9", "year": "2021" }, { "DOI": "10.1016/j.coviro.2016.01.001", "article-title": "Type I interferons in viral control and immune regulation", "author": "Teijaro", "doi-asserted-by": "crossref", "first-page": "31", "journal-title": "Curr. Opin. Virol.", "key": "ref_35", "volume": "16", "year": "2016" }, { "DOI": "10.1016/j.coviro.2013.05.019", "article-title": "Viral modulation of programmed necrosis", "author": "Kaiser", "doi-asserted-by": "crossref", "first-page": "296", "journal-title": "Curr. Opin. Virol.", "key": "ref_36", "volume": "3", "year": "2013" }, { "DOI": "10.1038/s41392-021-00679-0", "article-title": "The signal pathways and treatment of cytokine storm in COVID-19", "author": "Yang", "doi-asserted-by": "crossref", "first-page": "255", "journal-title": "Signal Transduct. Target. Ther.", "key": "ref_37", "volume": "6", "year": "2021" }, { "article-title": "Role of IL-6 and TNF in thermoregulation and survival during sepsis in mice", "author": "Leon", "first-page": "R269", "journal-title": "Am. J. Physiol.", "key": "ref_38", "volume": "275", "year": "1998" }, { "DOI": "10.3892/etm.2021.10942", "article-title": "Lactobacillus plantarum induces innate cytokine responses that potentially provide a protective benefit against COVID-19: A single-arm, double-blind, prospective trial combined with an in vitro cytokine response assay", "author": "Kageyama", "doi-asserted-by": "crossref", "first-page": "20", "journal-title": "Exp. Ther. Med.", "key": "ref_39", "volume": "23", "year": "2022" }, { "DOI": "10.3389/fnut.2021.789242", "article-title": "Boosting Vaccine-Elicited Respiratory Mucosal and Systemic COVID-19 Immunity in Mice with the Oral Lactobacillus Plantarum", "author": "Xu", "doi-asserted-by": "crossref", "first-page": "789242", "journal-title": "Front. Nutr.", "key": "ref_40", "volume": "8", "year": "2021" }, { "DOI": "10.1053/j.gastro.2021.09.009", "article-title": "Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?", "author": "Lau", "doi-asserted-by": "crossref", "first-page": "9", "journal-title": "Gastroenterology", "key": "ref_41", "volume": "162", "year": "2022" }, { "DOI": "10.1007/s13668-021-00375-z", "article-title": "Impact of COVID-19 on the Intestinal Microbiome", "author": "Sankararaman", "doi-asserted-by": "crossref", "first-page": "300", "journal-title": "Curr. Nutr. Rep.", "key": "ref_42", "volume": "10", "year": "2021" }, { "key": "ref_43", "unstructured": "(2022, September 28). Probiotics in Food: Health and Nutritional Properties and Guidelines for Evaluation. Available online: https://www.fao.org/3/a0512e/a0512e.pdf." }, { "DOI": "10.1093/cid/ciaa709", "article-title": "Alterations of the Gut Microbiota in Patients with Coronavirus Disease 2019 or H1N1 Influenza", "author": "Gu", "doi-asserted-by": "crossref", "first-page": "2669", "journal-title": "Clin. Infect. Dis.", "key": "ref_44", "volume": "71", "year": "2020" }, { "DOI": "10.1513/AnnalsATS.201503-133AW", "article-title": "The Gut-Lung Axis in Respiratory Disease", "author": "Marsland", "doi-asserted-by": "crossref", "first-page": "S150", "journal-title": "Ann. Am. Thorac. Soc.", "key": "ref_45", "volume": "12", "year": "2015" }, { "DOI": "10.3389/fimmu.2019.02754", "article-title": "Immunomodulating Activity and Therapeutic Effects of Short Chain Fatty Acids and Tryptophan Post-Biotics in Inflammatory Bowel Disease", "author": "Russo", "doi-asserted-by": "crossref", "first-page": "2754", "journal-title": "Front. Immunol.", "key": "ref_46", "volume": "10", "year": "2019" }, { "DOI": "10.1016/j.ebiom.2021.103293", "article-title": "Short chain fatty acids and its producing organisms: An overlooked therapy for IBD?", "author": "Deleu", "doi-asserted-by": "crossref", "first-page": "103293", "journal-title": "EBioMedicine", "key": "ref_47", "volume": "66", "year": "2021" }, { "DOI": "10.1016/j.cell.2017.01.022", "article-title": "Mining the Human Gut Microbiota for Immunomodulatory Organisms", "author": "Sefik", "doi-asserted-by": "crossref", "first-page": "928", "journal-title": "Cell", "key": "ref_48", "volume": "168", "year": "2017" }, { "DOI": "10.1006/biol.1997.0099", "article-title": "Mechanism of inactivation of enveloped viruses by the biosurfactant surfactin from Bacillus subtilis", "author": "Vollenbroich", "doi-asserted-by": "crossref", "first-page": "289", "journal-title": "Biologicals", "key": "ref_49", "volume": "25", "year": "1997" }, { "DOI": "10.1164/rccm.202005-1583OC", "article-title": "Characterization of the Inflammatory Response to Severe COVID-19 Illness", "author": "McElvaney", "doi-asserted-by": "crossref", "first-page": "812", "journal-title": "Am. J. Respir. Crit. Care Med.", "key": "ref_50", "volume": "202", "year": "2020" }, { "DOI": "10.3389/fimmu.2020.610300", "article-title": "Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases", "author": "Carsetti", "doi-asserted-by": "crossref", "first-page": "610300", "journal-title": "Front. Immunol.", "key": "ref_51", "volume": "11", "year": "2020" }, { "DOI": "10.1016/j.jaci.2020.07.001", "article-title": "The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection", "author": "Copaescu", "doi-asserted-by": "crossref", "first-page": "518", "journal-title": "J. Allergy Clin. Immunol.", "key": "ref_52", "volume": "146", "year": "2020" }, { "DOI": "10.1111/imm.13223", "article-title": "Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China", "author": "Tan", "doi-asserted-by": "crossref", "first-page": "261", "journal-title": "Immunology", "key": "ref_53", "volume": "160", "year": "2020" }, { "DOI": "10.1093/cid/ciaa851", "article-title": "Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load on Risk of Intubation and Mortality among Hospitalized Patients with Coronavirus Disease 2019", "author": "Magleby", "doi-asserted-by": "crossref", "first-page": "e4197", "journal-title": "Clin. Infect. Dis.", "key": "ref_54", "volume": "73", "year": "2021" }, { "DOI": "10.1038/nrd.2018.45", "article-title": "Interleukin-6: Designing specific therapeutics for a complex cytokine", "author": "Garbers", "doi-asserted-by": "crossref", "first-page": "395", "journal-title": "Nat. Rev. Drug Discov.", "key": "ref_55", "volume": "17", "year": "2018" }, { "article-title": "Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19)", "author": "Umakanthan", "first-page": "753", "journal-title": "Postgrad. Med. J.", "key": "ref_56", "volume": "96", "year": "2020" } ], "reference-count": 56, "references-count": 56, "relation": {}, "resource": { "primary": { "URL": "https://www.mdpi.com/2072-6643/15/3/488" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Food Science", "Nutrition and Dietetics" ], "subtitle": [], "title": "Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves Outcomes of Mild COVID-19", "type": "journal-article", "volume": "15" }