{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T12:19:09Z","timestamp":1764764349059,"version":"3.46.0"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Daiwa Pharmaceutical Co., Ltd., Tokyo, Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: MGN-3\/Biobran (BRM4, Lentin Plus or Ribraxx) is a natural, rice bran-derived arabinoxylan immunoceutical that modulates the adaptive immune response to viral infections. In response to bacterial infections, basophils act as \u201cfirst responders\u201d and are also associated with modulation of the adaptive immune response. The maturation of pluripotent CD34+ stem cells into basophils is supported by the cytokine interleukin-3 (IL-3). The aim was to test the hypothesis that modulation of the adaptive immune response in bacterial infection by MGN-3\/Biobran entails a basophilic response. The tick-related disorder Lyme borreliosis was chosen as the disease model; tick bites are associated with cutaneous IL-3-mediated basophil recruitment. Materials and Methods: A three-month randomised double-blind placebo-controlled trial was conducted in patients with a history of borreliosis who were suffering from symptoms attributable to this disorder. The immunoceutical group received oral Biobran; the dosage for both groups was 1 g thrice daily. Both groups were matched for age, sex, and ethnicity. Results: A higher percentage of basophil count occurred in the immunoceutical group (p = 0.038). The final general linear model included the group (immunoceutical\/placebo) and change in fatigue assessed by the 11-item Chalder Fatigue Questionnaire (CFQ) (r2 = 0.63; p = 0.0066). The change in basophil count was positively correlated with CFQ change (rs = 0.633; p = 0.020); only the immunoceutical group showed a positive correlation. Conclusions: These results support the hypothesis being tested. Basophils may modulate the adaptive immune response by acting as immunoregulatory cells. They can regulate the functioning of type 2 T-helper lymphocytes, enhance immunological memory, and present antigens to CD8 T lymphocytes. Further studies are needed to clarify potential mechanistic factors and the timing of this basophilic response.<\/jats:p>","DOI":"10.3390\/medicina61122156","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T11:29:30Z","timestamp":1764761370000},"page":"2156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Basophilic Response in Patients with Persistent Symptoms Attributed to Lyme Borreliosis Treated with Hydrolysed Arabinoxylan Rice Bran"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6101-0139","authenticated-orcid":false,"given":"Basant K.","family":"Puri","sequence":"first","affiliation":[{"name":"Cambridge Advanced Research, Cambridge CB21, UK"},{"name":"Department of Psychology, Neapolis University Pafos, 8042 Pafos, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8521-6534","authenticated-orcid":false,"given":"Gary S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Southampton, Southampton SO17, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5200-0406","authenticated-orcid":false,"given":"Georgia","family":"Tuckey","sequence":"additional","affiliation":[{"name":"The Clinical Department, TBD Clinic, Worthing BN14, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5222-2908","authenticated-orcid":false,"given":"Lisa","family":"Wyness","sequence":"additional","affiliation":[{"name":"The Clinical Department, TBD Clinic, Worthing BN14, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reine","family":"Corley","sequence":"additional","affiliation":[{"name":"The Clinical Department, TBD Clinic, Worthing BN14, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0285-7177","authenticated-orcid":false,"given":"Lucy","family":"Monaghan","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy, Isle of Wight NHS Trust, Newport PO30, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7186-8323","authenticated-orcid":false,"given":"Sari J.","family":"Arminen","sequence":"additional","affiliation":[{"name":"Cambridge Advanced Research, Cambridge CB21, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hunfeld, K.-P., and Gray, J. (2022). Characteristics of Borrelia burgdorferi sensu lato. Lyme Borreliosis, Springer International Publishing.","DOI":"10.1007\/978-3-030-93680-8"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hunfeld, K.-P., and Gray, J. (2022). The History, Epidemiology, Clinical Manifestations and Treatment of Lyme Borreliosis. Lyme Borreliosis, Springer International Publishing.","DOI":"10.1007\/978-3-030-93680-8"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Berende, A., ter Hofstede, H.J., Donders, A.R., van Middendorp, H., Kessels, R.P., Adang, E.M., Vos, F.J., Evers, A.W., and Kullberg, B.J. (2014). Persistent Lyme Empiric Antibiotic Study Europe (PLEASE)\u2014Design of a randomized controlled trial of prolonged antibiotic treatment in patients with persistent symptoms attributed to Lyme borreliosis. BMC Infect. Dis., 14.","DOI":"10.1186\/s12879-014-0543-y"},{"key":"ref_4","unstructured":"Huismans, B.-D., Klemann, W., and Heyl, S. (2015). Prolonged Antibiotic Therapy in PCR Confirmed Persistent Lyme Disease, Anchor Academic Publishing."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1093\/cid\/ciae302","article-title":"The Use of Long-term Antibiotics for Suppression of Bacterial Infections","volume":"79","author":"Horne","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/nri.2016.13","article-title":"Immunological memory: Lessons from the past and a look to the future","volume":"16","author":"Farber","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.chom.2018.12.006","article-title":"Innate and Adaptive Immune Memory: An Evolutionary Continuum in the Host\u2019s Response to Pathogens","volume":"25","author":"Netea","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1006\/bbrc.1997.8047","article-title":"Anti-HIV activity in vitro of MGN-3, an activated arabinoxylane from rice bran","volume":"243","author":"Ghoneum","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ooi, S.L., Micalos, P.S., and Pak, S.C. (2023). Modified rice bran arabinoxylan as a nutraceutical in health and disease-A scoping review with bibliometric analysis. PLoS ONE, 18.","DOI":"10.20944\/preprints202304.1154.v1"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ooi, S.L., Pak, S.C., Micalos, P.S., Schupfer, E., Lockley, C., Park, M.H., and Hwang, S.J. (2021). The Health-Promoting Properties and Clinical Applications of Rice Bran Arabinoxylan Modified with Shiitake Mushroom Enzyme-A Narrative Review. Molecules, 26.","DOI":"10.3390\/molecules26092539"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ooi, S.L., Micalos, P.S., and Pak, S.C. (2023). Modified Rice Bran Arabinoxylan by Lentinus edodes Mycelial Enzyme as an Immunoceutical for Health and Aging\u2013A Comprehensive Literature Review. Molecules, 28.","DOI":"10.20944\/preprints202307.0300.v1"},{"key":"ref_12","first-page":"e77694","article-title":"Modulation of Glutamatergic Burst Activity by Hydrolysed Arabinoxylan Rice Bran: A Multielectrode Array Study in Human-Induced Pluripotent Stem Cell-Derived Neurones and Astrocytes","volume":"17","author":"Puri","year":"2025","journal-title":"Cureus"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4149\/neo_2009_02_89","article-title":"BioBran-augmented maturation of human monocyte-derived dendritic cells","volume":"56","author":"Cholujova","year":"2009","journal-title":"Neoplasma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1177\/039463201102400412","article-title":"Activation of human monocyte-derived dendritic cells in vitro by the biological response modifier arabinoxylan rice bran (MGN-3\/Biobran)","volume":"24","author":"Ghoneum","year":"2011","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1177\/039463201402700408","article-title":"Mgn-3\/biobran enhances generation of cytotoxic CD8+ T cells via upregulation of dec-205 expression on dendritic cells","volume":"27","author":"Ghoneum","year":"2014","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ghoneum, M., Abdulmalek, S., and Fadel, H.H. (2023). Biobran\/MGN-3, an Arabinoxylan Rice Bran, Protects against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An In Vitro and In Silico Study. Nutrients, 15.","DOI":"10.3390\/nu15020453"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Agrawal, S., Agrawal, A., and Ghoneum, M. (2024). Biobran\/MGN-3, an Arabinoxylan Rice Bran, Exerts Anti-COVID-19 Effects and Boosts Immunity in Human Subjects. Nutrients, 16.","DOI":"10.3390\/nu16060881"},{"key":"ref_18","first-page":"132","article-title":"The orally administration of the Hydrolysis Rice Bran prevents a common cold syndrome for the elderly people based on immunomodulatory function","volume":"20","author":"Tazawa","year":"2003","journal-title":"J. Tradit. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Elsaid, A.F., Agrawal, S., Agrawal, A., and Ghoneum, M. (2021). Dietary Supplementation with Biobran\/MGN-3 Increases Innate Resistance and Reduces the Incidence of Influenza-like Illnesses in Elderly Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial. Nutrients, 13.","DOI":"10.3390\/nu13114133"},{"key":"ref_20","unstructured":"Punt, J., Stranford, S.A., Jones, P.P., and Owen, J.A. (2019). Kuby Immunology, W.H. Freeman\/Macmillan Learning. [8th ed.]."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0021-9975(08)80204-6","article-title":"The eosinophil","volume":"108","author":"Jones","year":"1993","journal-title":"J. Comp. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1093\/icb\/icz037","article-title":"Avian Health across the Landscape: Nestling Immunity Covaries with Changing Landcover","volume":"59","author":"Merrill","year":"2019","journal-title":"Integr. Comp. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/ni.1621","article-title":"Basophils enhance immunological memory responses","volume":"9","author":"Denzel","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/infdis\/jiu056","article-title":"Basophil expansion protects against invasive pneumococcal disease in mice","volume":"210","author":"Bischof","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1189\/jlb.71.4.557","article-title":"Differentiation of human basophils: An overview of recent advances and pending questions","volume":"71","author":"Arock","year":"2002","journal-title":"J. Leukoc. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ohta, T., Yoshikawa, S., Tabakawa, Y., Yamaji, K., Ishiwata, K., Shitara, H., Taya, C., Oh-Hora, M., Kawano, Y., and Miyake, K. (2017). Skin CD4(+) Memory T Cells Play an Essential Role in Acquired Anti-Tick Immunity through Interleukin-3-Mediated Basophil Recruitment to Tick-Feeding Sites. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01348"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0020-7519(73)90024-6","article-title":"Tick resistance: Basophils in skin reactions of resistant guinea pigs","volume":"3","author":"Allen","year":"1973","journal-title":"Int. J. Parasitol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.4049\/jimmunol.127.5.2163","article-title":"Cutaneous basophil responses and immune resistance of guinea pigs to ticks: Passive transfer with peritoneal exudate cells or serum","volume":"127","author":"Brown","year":"1981","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e081123","DOI":"10.1136\/bmj-2024-081123","article-title":"CONSORT 2025 statement: Updated guideline for reporting randomised trials","volume":"389","author":"Hopewell","year":"2025","journal-title":"BMJ"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0022-3999(93)90081-P","article-title":"Development of a fatigue scale","volume":"37","author":"Chalder","year":"1993","journal-title":"J. Psychosom. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1001\/archneur.1989.00520460115022","article-title":"The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus","volume":"46","author":"Krupp","year":"1989","journal-title":"Arch. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.mayocp.2012.10.013","article-title":"COMPASS 31: A refined and abbreviated Composite Autonomic Symptom Score","volume":"87","author":"Sletten","year":"2012","journal-title":"Mayo Clin. Proc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1023\/A:1016370925601","article-title":"Psychometric validation of an overactive bladder symptom and health-related quality of life questionnaire: The OAB-q","volume":"11","author":"Coyne","year":"2002","journal-title":"Qual. Life Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1001\/archotol.1996.01890140029007","article-title":"Development of the Tinnitus Handicap Inventory","volume":"122","author":"Newman","year":"1996","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_35","unstructured":"R Core Team (2022). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_36","unstructured":"JASP Team (JASP, 2025). JASP, 0.19.3."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1037\/met0000424","article-title":"Flexplot: Graphically-based data analysis","volume":"27","author":"Fife","year":"2022","journal-title":"Psychol. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer. [2nd ed.].","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_39","first-page":"148","article-title":"State-of-the-art review about basophil research in immunology and allergy: Is the time right to treat these cells with the respect they deserve?","volume":"10","author":"Chirumbolo","year":"2012","journal-title":"Blood Transfus."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.imlet.2011.02.012","article-title":"Basophils and mast cells: Underdog in immune regulation?","volume":"138","author":"Knol","year":"2011","journal-title":"Immunol. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1586\/eci.09.47","article-title":"Basophils as critical orchestrators of Th2-type immune responses","volume":"5","author":"Gibbs","year":"2009","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.coi.2010.01.012","article-title":"Role of basophils in the initiation of Th2 responses","volume":"22","author":"Sokol","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.4049\/jimmunol.0900332","article-title":"Basophils can directly present or cross-present antigen to CD8 lymphocytes and alter CD8 T cell differentiation into IL-10-producing phenotypes","volume":"183","author":"Kim","year":"2009","journal-title":"J. Immunol."},{"key":"ref_44","first-page":"183","article-title":"Posttreatment Lyme disease syndrome and myalgic encephalomyelitis\/chronic fatigue syndrome: A systematic review and comparison of pathogenesis","volume":"9","author":"Bai","year":"2023","journal-title":"Chronic Dis. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1055\/s-2007-971925","article-title":"Effects of prolonged exercise on brain ammonia and amino acids","volume":"19","author":"Guezennec","year":"1998","journal-title":"Int. J. Sports Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1177\/0394632016674954","article-title":"Arabinoxylan rice bran (Biobran) suppresses the viremia level in patients with chronic HCV infection: A randomized trial","volume":"29","author":"Salama","year":"2016","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"55","DOI":"10.15430\/JCP.2020.25.1.55","article-title":"Efficacy of Cereal-based oral nutrition supplement on nutritional status, inflammatory cytokine secretion and quality of life in cancer patients under cancer therapy","volume":"25","author":"Kim","year":"2020","journal-title":"J. Cancer Prev."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/12\/2156\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T12:15:11Z","timestamp":1764764111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/12\/2156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,3]]},"references-count":47,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["medicina61122156"],"URL":"https:\/\/doi.org\/10.3390\/medicina61122156","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,3]]}}}