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Review

Gut immune homeostasis: the immunomodulatory role of Bacillus clausii, from basic to clinical evidence

ORCID Icon, , ORCID Icon, ORCID Icon & ORCID Icon
Pages 717-729 | Received 13 Aug 2021, Accepted 31 May 2022, Published online: 19 Jun 2022

References

  • Vieira AT, Teixeira MM, Martins FS. The role of probiotics and prebiotics in inducing gut immunity. Front Immunol. 2013. 12. Dec(4):445.
  • La Fata G, Weber P, Mohajeri MH. Probiotics and the gut immune system: indirect regulation. Probiotics Antimicrob Proteins. 2018 Mar;10(1):11–21.
  • Johansson ME, Sjovall H, Hansson GC. The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol. 2013 Jun;10(6):352–361.
  • Bron PA, Kleerebezem M, Brummer RJ, et al. Can probiotics modulate human disease by impacting intestinal barrier function? Br J Nutr. 2017 Jan;117(1):93–107.
  • Schenk M, Mueller C. The mucosal immune system at the gastrointestinal barrier. Best Pract Res Clin Gastroenterol. 2008;22(3):391–409.
  • Flannigan KL, Geem D, Harusato A, et al. Intestinal antigen-presenting cells: Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trialtion. Am J Pathol. 2015 Jul;185(7):1809–1819.
  • Sanders ME, Merenstein DJ, Reid G, et al. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat Rev Gastroenterol Hepatol. 2019 Oct;16(10):605–616.
  • Azad MAK, Sarker M, Wan D. Immunomodulatory Effects of Probiotics on Cytokine Profiles. Biomed Res Int. 2018;2018:8063647.
  • Lycke NY, Bemark M. The regulation of gut mucosal IgA B-cell responses: recent developments. Mucosal Immunol. 2017 Nov;10(6):1361–1374.
  • Wilson NJ, Boniface K, Chan JR, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007 Sep;8(9):950–957.
  • Saravia J, Chapman NM, Helper CH. T cell differentiation. Cell Mol Immunol. 2019 Jul;16(7):634–643.
  • Taylor A, Verhagen J, Blaser K, et al. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology. 2006 Apr;117(4):433–442.
  • Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res. 2020 Jun;30(6):492–506.
  • Kostic AD, Chun E, Meyerson M, et al. Microbes and inflammation in colorectal cancer. Cancer Immunol Res. 2013 Sep;1(3):150–157.
  • Buccigrossi V, Nicastro E, Guarino A. Functions of intestinal microflora in children. Curr Opin Gastroenterol. 2013 Jan;29(1):31–38.
  • Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989 Nov 18;299(6710):1259–1260.
  • Jain N. The early life education of the immune system: moms, microbes and (missed) opportunities. Gut Microbes. 2020 Nov 9;12(1):1824564.
  • Lazar V, Ditu LM, Pircalabioru GG, et al. Aspects of gut microbiota and immune system interactions in infectious diseases, immunopathology, and cancer. Front Immunol. 2018;9:1830.
  • Al Nabhani Z, Eberl G. Imprinting of the immune system by the microbiota early in life. Mucosal Immunol. 2020 Mar;13(2):183–189.
  • Marques AH, O’Connor TG, Roth C, et al. The influence of maternal prenatal and early childhood nutrition and maternal prenatal stress on offspring immune system development and neurodevelopmental disorders. Front Neurosci. 2013;7:120.
  • Ardissone AN, de la Cruz DM, Davis-Richardson AG, et al. Meconium microbiome analysis identifies bacteria correlated with premature birth. PLoS One. 2014;9(3):e90784.
  • Nagpal R, Tsuji H, Takahashi T, et al. Sensitive quantitative analysis of the meconium bacterial microbiota in healthy term infants born vaginally or by cesarean section. Front Microbiol. 2016;7:1997.
  • Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11971–11975.
  • Azad MB, Konya T, Maughan H, et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. Can Med Assoc J. 2013;185(5):385–394.
  • Benno YS K, Mitsuoka T. The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol Immunol. 1984;28(9):975–986.
  • Gomez-Llorente C, Plaza-Diaz J, Aguilera M, et al. Three main factors define changes in fecal microbiota associated with feeding modality in infants. J Pediatr Gastroenterol Nutr. 2013 Oct;57(4):461–466.
  • Stewart CJ, Ajami NJ, O’Brien JL, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018 Oct;562(7728):583–588.
  • Laursen MF, Andersen LBB, Michaelsen KF, et al. Infant gut microbiota development is driven by transition to family foods independent of maternal obesity. mSphere. 2016;1:1.
  • Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol. 2013 Jan;6(1):39–51.
  • Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506–514.
  • Guarner FS ME, Eliakim R, Fedorak R, et al., World Gastroenterology Guidelines: probiotics and prebiotics. World Gastroenterol Organ. 2017;
  • Asahara T, Shimizu K, Nomoto K, et al. Probiotic bifidobacteria protect mice from lethal infection with Shiga toxin-producing Escherichia coli O157:H7. Infect Immun. 2004 Apr;72(4):2240–2247.
  • Corr SC, Li Y, Riedel CU, et al. Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118. Proc Nat Acad Sci. 2007; 104(18):7617–7621.
  • Cleusix V, Lacroix C, Vollenweider S, et al. Inhibitory activity spectrum of reuterin produced by Lactobacillus reuteri against intestinal bacteria. BMC Microbiol. 2007 Nov;12(7):101.
  • Tytgat HL, Douillard FP, Reunanen J, et al. Lactobacillus rhamnosus GG Outcompetes Enterococcus faecium via Mucus-Binding Pili: evidence for a Novel and heterospecific probiotic mechanism. Appl Environ Microbiol. 2016 Oct 1;82(19):5756–5762.
  • Altenhoefer A, Oswald S, Sonnenborn U, et al. The probioticEscherichia colistrain Nissle 1917 interferes with invasion of human intestinal epithelial cells by different enteroinvasive bacterial pathogens. FEMS Immunol Med Microbiol. 2004;40(3):223–229.
  • Sassone-Corsi M, Nuccio SP, Liu H, et al. Microcins mediate competition among Enterobacteriaceae in the inflamed gut. Nature. 2016 Dec 8;540(7632):280–283.
  • Castagliuolo I, LaMont JT, Nikulasson ST, et al. Saccharomyces boulardii protease inhibits Clostridium difficile toxin A effects in the rat ileum. Infect Immun. 1996 Dec;64(12):5225–5232.
  • Mennigen R, Nolte K, Rijcken E, et al. Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am J Physiol Gastrointest Liver Physiol. 2009 May;296(5):G1140–9.
  • Hummel S, Veltman K, Cichon C, et al. Differential targeting of the E-Cadherin/beta-Catenin complex by gram-positive probiotic lactobacilli improves epithelial barrier function. Appl Environ Microbiol. 2012 Feb;78(4):1140–1147.
  • Zyrek AA, Cichon C, Helms S, et al. Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCzeta redistribution resulting in tight junction and epithelial barrier repair. Cell Microbiol. 2007 Mar;9(3):804–816.
  • Mack DR, Ahrne S, Hyde L, et al. Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut. 2003 Jun;52(6):827–833.
  • Niers LE, Timmerman HM, Rijkers GT, et al. Identification of strong interleukin-10 inducing lactic acid bacteria which down-regulate T helper type 2 cytokines. Clin Exp Allergy. 2005 Nov;35(11):1481–1489.
  • Feleszko W, Jaworska J, Rha RD, et al. Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma. Clin Exp Allergy. 2007 Apr;37(4):498–505.
  • Chen YH, Wu CS, Chao YH, et al. Lactobacillus pentosus GMNL-77 inhibits skin lesions in imiquimod-induced psoriasis-like mice. J Food Drug Anal. 2017 Jul;25(3):559–566.
  • Frank MG, Fonken LK, Watkins LR, et al. Could Probiotics Be Used to Mitigate Neuroinflammation? ACS Chem Neurosci. 2019 Jan 16;10(1):13–15.
  • Reber SO, Siebler PH, Donner NC, et al. Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice. Proc Natl Acad Sci U S A. 2016 May 31;113(22):E3130–9.
  • Aindelis G, Chlichlia K. Modulation of Anti-Tumour Immune Responses by Probiotic Bacteria. Vaccines (Basel). 2020 Jun 21;8:2.
  • Habil N, Abate W, Beal J, et al. Heat-killed probiotic bacteria differentially regulate colonic epithelial cell production of human beta-defensin-2: dependence on inflammatory cytokines. Benef Microbes. 2014 Dec;5(4):483–495.
  • Wehkamp J, Harder J, Wehkamp K, et al. NF-kappaB- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium. Infect Immun. 2004 Oct;72(10):5750–5758.
  • Paolillo R, Romano Carratelli C, Sorrentino S, et al. Immunomodulatory effects of Lactobacillus plantarum on human colon cancer cells. Int Immunopharmacol. 2009;9(11):1265–1271.
  • Ghadimi D, Vrese M, Heller KJ, et al. Effect of natural commensal-origin DNA on toll-like receptor 9 (TLR9) signaling cascade, chemokine IL-8 expression, and barrier integritiy of polarized intestinal epithelial cells. Inflamm Bowel Dis. 2010;16(3):410–427.
  • Yang YJ, Chuang CC, Yang HB, et al. Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFkappaB pathways. BMC Microbiol. 2012 Mar;19(12):38.
  • Frei R, Akdis M, O’Mahony L. Prebiotics, probiotics, synbiotics, and the immune system: experimental data and clinical evidence. Curr Opin Gastroenterol. 2015 Mar;31(2):153–158.
  • Zeng W, Shen J, Bo T, et al. Cutting edge: probiotics and fecal microbiota transplantation in immunomodulation. J Immunol Res. 2019;2019:1603758.
  • Kalliomäki M, Salminen S, Arvilommi H, et al. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet. 2001;357(9262):1076–1079.
  • Kim SO, Ah YM, Yu YM, et al. Effects of probiotics for the treatment of atopic dermatitis: a meta-analysis of randomized controlled trials. Ann Allergy Asthma Immunol. 2014 Aug;113(2):217–226.
  • Klewicka E, Cukrowska B, Libudzisz Z, et al. Changes in gut microbiota in children with atopic dermatitis administered the bacteria lactobacillus casei DN – 114001. Pol J Microbiol. 2011;60(4):329–333.
  • Kouchaki E, Tamtaji OR, Salami M, et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2017;36(5):1245–1249.
  • Leblhuber F, Steiner K, Schuetz B, et al. Probiotic Supplementation in Patients with Alzheimer’s Dementia - An explorative intervention study. Curr Alzheimer Res. 2018;15(12):1106–1113.
  • Michail SK, Stolfi A, Johnson T, et al. Efficacy of probiotics in the treatment of pediatric atopic dermatitis: a meta-analysis of randomized controlled trials. Ann Allergy Asthma Immunol. 2008 Nov;101(5):508–516.
  • Navarro-Lopez V, Martinez-Andres A, Ramirez-Bosca A, et al. Efficacy and safety of oral administration of a mixture of probiotic strains in patients with psoriasis: a randomized controlled clinical trial. Acta Derm Venereol. 2019 Nov 1;99(12):1078–1084.
  • Vijayashankar M, Raghunath N. Pustular psoriasis responding to Probiotics – a new insight. Our Dermatol Online. 2012;3(4):326–329
  • Emre İE, Eroğlu Y, Kara A, et al. The effect of probiotics on prevention of upper respiratory tract infections in the paediatric community – a systematic review. Benef Microbes. 2020;11(3):201–211.
  • Groeger D, O’Mahony L, Murphy EF, et al. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. 2014;4(4):325–339.
  • Salami M, Kouchaki E, Asemi Z, et al. How probiotic bacteria influence the motor and mental behaviors as well as immunological and oxidative biomarkers in multiple sclerosis? A double blind clinical trial. J Funct Foods. 2019;52:8–13.
  • Tenorio-Jimenez C, Martinez-Ramirez MJ, Gil A, et al. Effects of probiotics on metabolic syndrome: a systematic review of randomized clinical Trials. Nutrients. 2020 Jan 1;12(1):124.
  • Hickson M. Probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection. Therap Adv Gastroenterol. 2011 May;4(3):185–197.
  • Homan M. Are probiotics useful inHelicobacter pylorieradication? World J Gastroenterol. 2015;21:37.
  • Lei WT, Shih PC, Liu SJ, et al. Effect of Probiotics and prebiotics on immune response to influenza vaccination in adults: A systematic review and meta-analysis of randomized controlled trials. Nutrients. 2017 Oct 27;9:11.
  • McFarland LV, Ozen M, Dinleyici EC, et al. Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections. World J Gastroenterol. 2016 Mar 21;22(11):3078–3104.
  • Miller LE, Lehtoranta L, Lehtinen MJ. Short-term probiotic supplementation enhances cellular immune function in healthy elderly: systematic review and meta-analysis of controlled studies. Nutr Res. 2019 Apr;64:1–8.
  • Ozen M, Kocabas Sandal G, Dinleyici EC. Probiotics for the prevention of pediatric upper respiratory tract infections: a systematic review. Expert Opin Biol Ther. 2014;15(1):9–20.
  • Szajewska H, Horvath A, Kolodziej M. Systematic review with meta-analysis: saccharomyces boulardii supplementation and eradication of Helicobacter pylori infection. Aliment Pharmacol Ther. 2015 Jun;41(12):1237–1245.
  • Zimmermann P, Curtis N. The influence of probiotics on vaccine responses - A systematic review. Vaccine. 2018 Jan 4;36(2):207–213.
  • Elshaghabee FMF, Rokana N, Gulhane RD, et al. Bacillus as potential probiotics: status, concerns, and future perspectives. Front Microbiol. 2017;8:1490.
  • Hong HA, Duc LH, Cutting SM, et al. The use of bacterial spore formers as probiotics. FEMS Microbiol Rev. 2005 Sep;29(4): 813–835.
  • Tam NK, Uyen NQ, Hong HA, et al. The intestinal life cycle of Bacillus subtilis and close relatives. J Bacteriol. 2006 Apr;188(7):2692–2700.
  • Hoyles L, Honda H, Logan NA, et al. Recognition of greater diversity of Bacillus species and related bacteria in human faeces. Res Microbiol. 2012;163(1):3–13.
  • Khatri I, Sharma G, Subramanian S. Composite genome sequence of Bacillus clausii, a probiotic commercially available as Enterogermina((R)), and insights into its probiotic properties. BMC Microbiol. 2019 Dec 30;19(1):307.
  • Lopetuso LR, Scaldaferri F, Franceschi F, et al. Bacillus clausii and gut homeostasis: state of the art and future perspectives. Expert Rev Gastroenterol Hepatol.2016;1–6.https://doi.org/10.1080/17474124.2016.1200465
  • Abbrescia AP, Papa LL, Gaballo S, et al. Sensitivity of Bacillus clausii Strains in Commercial Preparation. Clin Immunol Endocr Metab Drugs. 2014;1:102–110.
  • Bozdogan B, Galopin S, Gerbaud G, et al. Chromosomal aadD2 encodes an aminoglycoside nucleotidyltransferase in Bacillus clausii. Antimicrob Agents Chemother. 2003 Apr;47(4):1343–1346.
  • Bozdogan B, Galopin S, Leclercq R. Characterization of a new erm-related macrolide resistance gene present in probiotic strains of Bacillus clausii. Appl Environ Microbiol. 2004 Jan;70(1):280–284.
  • Galopin S, Cattoir V, Leclercq R. A chromosomal chloramphenicol acetyltransferase determinant from a probiotic strain of Bacillus clausii. FEMS Microbiol Lett. 2009 Jun;296(2):185–189.
  • Girlich D, Leclercq R, Naas T, et al. Molecular and biochemical characterization of the chromosome-encoded class A beta-lactamase BCL-1 from Bacillus clausii. Antimicrob Agents Chemother. 2007 Nov;51(11):4009–4014.
  • Nista EC, Candelli M, Cremonini F, et al. Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori treatment: randomized, double-blind, placebo controlled trial. Aliment Pharmacol Ther. 2004 Nov 15;20(10):1181–1188.
  • Urdaci MC, Bressollier P, Pinchuk I. Bacillus clausii probiotic strains: antimicrobial and immunomodulatory activities. J Clin Gastroenterol. 2004 Jul;38(6 Suppl):S86–90.
  • Lefevre M, Racedo SM, Ripert G, et al. Probiotic strain Bacillus subtilis CU1 stimulates immune system of elderly during common infectious disease period: a randomized, double-blind placebo-controlled study. Immun Ageing. 2015;12:24.
  • Nyangale EP, Farmer S, Keller D, et al. Effect of prebiotics on the fecal microbiota of elderly volunteers after dietary supplementation of Bacillus coagulans GBI-30, 6086. Anaerobe. 2014;30:75–81.
  • Nyangale EP, Farmer S, Keller D, et al. Corrigendum to “Effects of prebiotics on the fecal microbiota of elderly volunteers after dietary supplementation of Bacillus coagulans GBI-30, 6086” [Anaerobe 30 (2014) 75–81]. Anaerobe. 2015;34:187.
  • Gupta AK, Maity C. Efficacy and safety of Bacillus coagulans LBSC in irritable bowel syndrome: a prospective, interventional, randomized, double-blind, placebo-controlled clinical study [CONSORT Compliant]. Medicine (Baltimore). 2021 Jan 22;100(3):e23641.
  • Sudha MR, Jayanthi N, Aasin M, et al. Efficacy of Bacillus coagulans Unique IS2 in treatment of irritable bowel syndrome in children: a double blind, randomised placebo controlled study. Benef Microbes. 2018;9(4):563–572.
  • Urgesi R, Casale C, Pistelli R, et al. A randomized double-blind placebo-controlled clinical trial on efficacy and safety of association of simethicone and Bacillus coagulans (Colinox(R)) in patients with irritable bowel syndrome. Eur Rev Med Pharmacol Sci. 2014;18(9):1344–1353.
  • Minamida K, Nishimura M, Miwa K, et al. Effects of dietary fiber with Bacillus coagulans lilac-01 on bowel movement and fecal properties of healthy volunteers with a tendency for constipation. Biosci Biotechnol Biochem. 2015;79(2):300–306.
  • Horosheva TV, Vodyanoy V, Sorokulova I. Efficacy of Bacillus probiotics in prevention of antibiotic‐associated diarrhoea: a randomized, double‐blind, placebo‐controlled clinical trial. JMM Case Rep. 2014;1:3.
  • Pinchuk IV, Bressollier P, Verneuil B, et al. In vitro anti-Helicobacter pylori activity of the probiotic strain Bacillus subtilis 3 is due to secretion of antibiotics. Antimicrob Agents Chemother. 2001 Nov;45(11):3156–3161.
  • Abdhul K, Ganesh M, Shanmughapriya S, et al. Bacteriocinogenic potential of a probiotic strain Bacillus coagulans [BDU3] from Ngari. Int J Biol Macromol. 2015 Aug;79:800–806.
  • Lee KH, Jun KD, Kim WS, et al. Partial characterization of polyfermenticin SCD, a newly identified bacteriocin of Bacillus polyfermenticus. Lett Appl Microbiol. 2001 Mar;32(3):146–151.
  • Khochamit N, Siripornadulsil S, Sukon P, et al. Antibacterial activity and genotypic-phenotypic characteristics of bacteriocin-producing Bacillus subtilis KKU213: potential as a probiotic strain. Microbiol Res. 2015 Jan;170:36–50.
  • Duysburgh C, Van den Abbeele P, Krishnan K, et al. A synbiotic concept containing spore-forming Bacillus strains and a prebiotic fiber blend consistently enhanced metabolic activity by modulation of the gut microbiome in vitro. Int J Pharm X. 2019 Dec;1:100021.
  • Ji J, Hu SL, Cui ZW, et al. Probiotic Bacillus amyloliquefaciens mediate M1 macrophage polarization in mouse bone marrow-derived macrophages. Arch Microbiol. 2013 May;195(5):349–356.
  • Guo L, Meng M, Wei Y, et al. Protective Effects of Live Combined B. subtilis and E. faecium in polymicrobial sepsis through modulating activation and transformation of macrophages and mast cells. Front Pharmacol. 2018;9:1506.
  • Paynich ML, Jones-Burrage SE, Knight KL. Exopolysaccharide from Bacillus subtilis Induces Anti-Inflammatory M2 macrophages that prevent T cell-mediated disease. J Immunol. 2017 Apr 1;198(7):2689–2698.
  • Foligne B, Peys E, Vandenkerckhove J, et al. Spores from two distinct colony types of the strain Bacillus subtilis PB6 substantiate anti-inflammatory probiotic effects in mice. Clin Nutr. 2012 Dec;31(6):987–994.
  • Abhari K, Shekarforoush SS, Hosseinzadeh S, et al. The effects of orally administered Bacillus coagulans and inulin on prevention and progression of rheumatoid arthritis in rats. Food Nutr Res. 2016;60:30876.
  • Appel-da-Silva MC, Narvaez GA, Perez LRR, et al. Saccharomyces cerevisiae var. boulardii fungemia following probiotic treatment. Med Mycol Case Rep. 2017;18:15–17.
  • Bertelli C, Pillonel T, Torregrossa A, et al. Bifidobacterium longum bacteremia in preterm infants receiving probiotics. Clinl Infect Dis. 2015;60(6):924–927.
  • Meini S, Laureano R, Fani L, et al. Breakthrough Lactobacillus rhamnosus GG bacteremia associated with probiotic use in an adult patient with severe active ulcerative colitis: case report and review of the literature. Infection. 2015;43(6):777–781.
  • Munoz P, Bouza E, Cuenca-Estrella M, et al. Saccharomyces cerevisiae Fungemia: an Emerging Infectious Disease. Clinl Infect Dis. 2005;40(11):1625–1634.
  • Khatri AM, Rai S, Shank C, et al. A tale of caution: prolonged Bacillus clausii bacteraemia after probiotic use in an immunocompetent child. Access Microbiol. 2021; 3: 3.
  • Joshi S, Udani S, Sen S, et al. Bacillus Clausii septicemia in a pediatric patient after treatment with probiotics. Pediatr Infect Dis J. 2019;38(9):e228–e230.
  • Pradhan B, Guha D, Ray P, et al. Comparative analysis of the effects of two probiotic bacterial strains on metabolism and innate immunity in the RAW 264.7 murine macrophage cell line. Probiotics Antimicrob Proteins. 2016 Jun;8(2):73–84.
  • Ahire JJ, Kashikar MS, Madempudi RS. Survival and Germination of Bacillus clausii UBBC07 Spores in in vitro Human Gastrointestinal Tract Simulation Model and Evaluation of Clausin Production. Front Microbiol. 2020;11:1010.
  • Pradhan B, Guha D, Naik AK, et al. Probiotics L. acidophilus and B. clausii modulate gut microbiota in Th1- and Th2-Biased Mice to Ameliorate salmonella typhimurium-induced diarrhea. Probiotics Antimicrob Proteins. 2019 Sep;11(3):887–904.
  • Bouhss A, Al-Dabbagh B, Vincent M, et al. Specific interactions of clausin, a new lantibiotic, with lipid precursors of the bacterial cell wall. Biophys J. 2009 Sep 2;97(5):1390–1397.
  • Paparo L, Tripodi L, Bruno C, et al. Protective action of Bacillus clausii probiotic strains in an in vitro model of Rotavirus infection. Sci Rep. 2020 Jul 28;10(1):12636.
  • Lippolis R, Siciliano RA, Mazzeo MF, et al. Comparative secretome analysis of four isogenic Bacillus clausii probiotic strains. Proteome Sci. 2013 Jul 1;11(1):28.
  • Villeger R, Saad N, Grenier K, et al. Characterization of lipoteichoic acid structures from three probiotic Bacillus strains: involvement of D-alanine in their biological activity. Antonie Van Leeuwenhoek. 2014 Oct;106(4):693–706.
  • Gao F, Lucke-Wold BP, Li X, et al. Reduction of endothelial nitric oxide increases the adhesiveness of constitutive endothelial membrane ICAM-1 through Src-Mediated Phosphorylation. Front Physiol. 2018;6:8.
  • Ripert G, Racedo SM, Elie AM, et al. Secreted Compounds of the Probiotic Bacillus clausii Strain O/C inhibit the cytotoxic effects induced by clostridium difficile and bacillus cereus toxins. Antimicrob Agents Chemother. 2016 Jun;60(6):3445–3454.
  • Cenci G, Caldini G, Trotta F, et al. In vitro inhibitory activity of probiotic spore-forming bacilli against genotoxins. Lett Appl Microbiol. 2008 Mar;46(3):331–337.
  • Ghelardi E, Celandroni F, Salvetti S, et al. Survival and persistence of Bacillus clausii in the human gastrointestinal tract following oral administration as spore-based probiotic formulation. J Appl Microbiol. 2015;119(2):552–559.
  • Ianiro G, Rizzatti G, Plomer M, et al. Bacillus clausii for the treatment of acute diarrhea in children: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2018 Aug 12;10(8):1074.
  • De Castro JA, Kesavelu D, Lahiri KR, et al. Recommendations for the adjuvant use of the poly-antibiotic-resistant probiotic Bacillus clausii (O/C, SIN, N/ R,T) in acute, chronic, and antibiotic-associated diarrhea in children: consensus from Asian experts. Trop Dis Travel Med Vaccines. 2020;6:21.
  • de Castro JA, Guno MJV, Perez MO. Bacillus clausii as adjunctive treatment for acute community-acquired diarrhea among Filipino children: a large-scale, multicenter, open-label study (CODDLE). Trop Dis Travel Med Vaccines. 2019;5:14.
  • Sudha MR, Jayanthi N, Pandey DC, et al. Bacillus clausii UBBC-07 reduces severity of diarrhoea in children under 5 years of age: a double blind placebo controlled study. Benef Microbes. 2019;10(2):149–154.
  • Smiyan OI, Smiian-Horbunova KO, Bynda TP, et al. Optimization of the treatment of rotavirus infection in children by using Bacillus Clausii. Wiadomości Lekarskie. 2019; 72(7):1320–1323.
  • Plomer M, Iii Perez M, Greifenberg DM. Effect of Bacillus clausii capsules in reducing adverse effects associated with helicobacter pylori eradication therapy: a randomized, double-blind, controlled trial. Infect Dis Ther. 2020 Dec;9(4):867–878.
  • Ji J, Yang H. Using probiotics as supplementation for helicobacter pylori antibiotic therapy. Int J Mol Sci. 2020;21:3.
  • Di Caro ST H, Grillo A, Franceschi F, et al. Bacillus clausii effect on gene expression pattern in small bowel mucosa using DNA microarray analysis. Eur J Gastroenterol Hepatol. 2005;17:951–960.
  • Tewari VV, Dubey SK, Gupta G. Bacillus clausii for prevention of late-onset sepsis in preterm infants: a randomized controlled trial. J Trop Pediatr. 2015 Oct;61(5):377–385.
  • Chang HY, Chen JH, Chang JH, et al. Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: an updated meta-analysis. PLoS One. 2017;12(2):e0171579.
  • Bi LW, Yan BL, Yang QY, et al. Which is the best probiotic treatment strategy to prevent the necrotizing enterocolitis in premature infants: a network meta-analysis revealing the efficacy and safety. Medicine (Baltimore). 2019 Oct;98(41):e17521.
  • Beghetti I, Panizza D, Lenzi J, et al. Probiotics for preventing necrotizing enterocolitis in preterm infants: a network meta-analysis. Nutrients. 2021 9; 13(1): Jan.
  • Marseglia GL, Tosca M, Cirillo I, et al. Efficacy of Bacillus clausii spores in the prevention of recurrent respiratory infections in children: a pilot study. Ther Clin Risk Manag. 2007 3;Mar(1):13–17.
  • Ciprandi G, Tosca MA, Milanese M, et al. Cytokines evaluation in nasal lavage of allergic children after Bacillus clausii administration: a pilot study. Pediatr Allergy Immunol. 15(2): 148–151. 2004.
  • Ciprandi G, Vizzaccaro A, Cirillo I, et al. Bacillus clausii exerts immuno-modulatory activity in allergic subjects: a pilot study. Eur Ann Allergy Clin Immunol. 2005 Apr;37(4):129–134.