Recombinant Probiotic Preparations: Current State, Development and Application Prospects




genetic engineering, biotherapy, living microorganisms, cell-factory, metabolic disorders, immune stimulants, probiotic-based vaccines


The article is devoted to the latest achievements in the field of research, development, and implementation of various types of medicinal products based on recombinant probiotics. The benefits of probiotics, their modern use in medicine along with the most frequently used genera and species of probiotic microorganisms were highlighted. The medicinal and therapeutic activities of the studied probiotics were indicated. The review suggests various methods of creating recombinant probiotic microorganisms, including standard genetic engineering methods, as well as systems biology approaches and new methods of using the CRISPR-Cas system. The range of potential therapeutic applications of drugs based on recombinant probiotics was proposed. Special attention was paid to modern research on the creation of new, more effective recombinant probiotics that can be used for various therapeutic purposes. Considering the vast diversity of therapeutic applications of recombinant probiotics and ambiguous functions, their use for the potential treatment of various common human diseases (non-infectious and infectious diseases of the gastrointestinal tract, metabolic disorders, and allergic conditions) was investigated. The prospects for creating different types of vaccines based on recombinant probiotics together with the prospects for their implementation into medicine were considered. The possibilities of using recombinant probiotics in veterinary medicine, particularly for the prevention of domestic animal diseases, were reviewed. The prospects for the implementation of recombinant probiotics as vaccines and diagnostic tools for testing certain diseases as well as modeling the work of the human digestive system were highlighted. The risks of creation, application, including the issues related to the regulatory sphere regarding the use of new recombinant microorganisms, which can potentially enter the environment and cause unforeseen circumstances, were outlined.


Hanlon P, Sewalt V. GEMs: genetically engineered microorganisms and the regulatory oversight of their uses in modern food production. Crit Rev Food Sci Nutr. 2021;61(6):959-70. DOI: 10.1080/10408398.2020.1749026

Lanigan TM, Kopera HC, Saunders TL. Principles of genetic engineering. Genes (Basel). 2020 Mar 10;11(3):291. DOI: 10.3390/genes11030291

Chen J, Li X, Liu Y, Su T, Lin C, Shao L, et al. Engineering a probiotic strain of Escherichia coli to induce the regression of colorectal cancer through production of 5-aminolevulinic acid. Microb Biotechnol. 2021 Sep;14(5):2130-9. DOI: 10.1111/1751-7915.13894

Knott GJ, Doudna JA. CRISPR-Cas guides the future of genetic engineering. Science. 2018 Aug 31;361(6405):866-9. DOI: 10.1126/science.aat5011

Vailati-Riboni M, Palombo V, Loor JJ. What are omics sciences? In: Ametaj B, editor. Periparturient diseases of dairy cows. Cham: Springer; 2017. DOI: 10.1007/978-3-319-43033-1_1

Parello CS. Microbiomics. In: Sonis ST, Villa A, editors. Translational systems medicine and oral disease. Cambridge, MA: Academic Press; 2020. pp. 137-62. DOI: 10.1016/B978-0-12-813762-8.00006-2

Cullen CM, Aneja KK, Beyhan S, Cho CE, Woloszynek S, Convertino M, et al. Emerging priorities for microbiome research. Front Microbiol. 2020 Feb 19;11:136. DOI: 10.3389/fmicb.2020.00136

Santacroce L, Charitos IA, Bottalico L. A successful history: probiotics and their potential as antimicrobials. Expert Rev Anti Infect Ther. 2019 Aug;17(8):635-45. DOI: 10.1080/14787210.2019.1645597

Stavropoulou E, Bezirtzoglou E. Probiotics in medicine: a long debate. Front Immunol. 2020 Sep 25;11:2192. DOI: 10.3389/fimmu.2020.02192

Ventura M, Turroni F, van Sinderen D. Probiogenomics as a tool to obtain genetic insights into adaptation of probiotic bacteria to the human gut. Bioeng Bugs. 2012 Mar-Apr;3(2):73-9. DOI: 10.4161/bbug.18540

Mathipa MG, Thantsha MS. Probiotic engineering: towards development of robust probiotic strains with enhanced functional properties and for targeted control of enteric pathogens. Gut Pathog. 2017 May 8;9(1):28. DOI: 10.1186/s13099-017-0178-9

Probiotics in food: health and nutritional properties and guidelines for evaluation: Report of a Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria; Cordoba, Argentina; 2001 Oct 1-4.

Liong MT, editor. Probiotics: biology, genetics and health aspects. Berlin, Heidelberg: Springer Berlin Heidelberg; 2011. DOI: 10.1007/978-3-642-20838-6

Khalighi A, Behdani R, Kouhestani S. Probiotics: a comprehensive review of their classification, mode of action and role in human nutrition. In: Rao V, Rao LG, editors. Probiotics and prebiotics in human nutrition and health. InTech; 2016. DOI: 10.5772/63646

Khablenko A, Danylenko S, Yalovenko O, Duhan O, Potemskaia O. Potential of using Saccharomyces boulardii to produce fermented milk products. Food Sci Tech. 2022 Mar 1;16(1). DOI: 10.15673/fst.v16i1.2290

Ivanova A, Yalovenko O, Dugan, O. Human intestinal microbiome: scientific and practical principles and achievements. Proceedings of InterConf; 2021 Nov 10. p. 231-60. DOI: 10.51582/interconf.7-8.11.2021.024

Kumar M, Yadav AK, Verma V, Singh B, Mal G, Nagpal R, et al. Bioengineered probiotics as a new hope for health and diseases: an overview of potential and prospects. Future Microbiol. 2016;11(4):585-600. DOI: 10.2217/fmb.16.4

Singh B, Mal G, Gautam SK, Mukesh M. Designer probiotics: the next-gen high efficiency biotherapeutics. In: Advances in animal biotechnology. Cham: Springer International Publishing; 2019. p. 71-9. DOI: 10.1007/978-3-030-21309-1_7

Giani AM, Gallo GR, Gianfranceschi L, Formenti G. Long walk to genomics: history and current approaches to genome sequencing and assembly. Comput Struct Biotechnol J. 2019 Nov 17;18:9-19. DOI: 10.1016/j.csbj.2019.11.002

Mandal SM, Silva ON, Franco OL. Recombinant probiotics with antimicrobial peptides: a dual strategy to improve immune response in immunocompromised patients. Drug Discov Today. 2014 Aug;19(8):1045-50. DOI: 10.1016/j.drudis.2014.05.019

de Jesus LCL, Lima FA, Coelho-Rocha ND, Silva TF, Paz J, Azevedo V, et al. Recombinant probiotics and microbiota modulation as a good therapy for diseases related to the GIT. In: Salanță LC, editor. The health benefits of foods. IntechOpen; 2019. DOI: 10.5772/intechopen.88325

Alok A, Singh ID, Singh S, Kishore M, Jha PC, Iqubal MA. Probiotics: a new era of biotherapy. Adv Biomed Res. 2017 Mar 7;6(1):31. DOI: 10.4103/2277-9175.192625

Wieërs G, Belkhir L, Enaud R, Leclercq S, Philippart de Foy JM, Dequenne I, et al. How probiotics affect the microbiota? Front Cell Infect Microbiol. 2020 Jan 15;9:454. DOI: 10.3389/fcimb.2019.00454

Sharifi-Rad J, Rodrigues CF, Stojanović-Radić Z, Dimitrijević M, Aleksić A, Neffe-Skocińska K, et al. Probiotics: Versatile bioactive components in promoting human health. Medicina (Kaunas). 2020 Aug 27;56(9):433. DOI: 10.3390/medicina56090433

Attri S, Singh N, Nadda AK, Goel G. Probiotics and their potential applications: an introduction. In: Microorganisms for sustainability. Singapore: Springer Singapore; 2020. p. 1-26. DOI: 10.1007/978-981-15-6795-7_1

Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol. 2018 Mar;16(3):143-55. DOI: 10.1038/nrmicro.2017.157

Chen X, Lu Y, Chen T, Li R. The female vaginal microbiome in health and bacterial vaginosis. Front Cell Infect Microbiol. 2021 Apr 7;11:631972. DOI: 10.3389/fcimb.2021.631972

Bustamante M, Oomah BD, Oliveira WP, Burgos-Díaz C, Rubilar M, Shene C. Probiotics and prebiotics potential for the care of skin, female urogenital tract, and respiratory tract. Folia Microbiol (Praha). 2020 Apr;65(2):245-64. DOI: 10.1007/s12223-019-00759-3

Dhanaraju R, Rao DN. The human microbiome: an acquired organ? Resonance. 2022 Feb;27(2):247-72. DOI: 10.1007/s12045-022-1312-7

Ivanova A, Yalovenko O, Dugan, O. Fecal microbiota transplantation: achievements, practical significance, problems and prospects. Proceedings of InterConf; 2021 Oct 11. p. 291-306. DOI: 10.51582/interconf.7-8.10.2021.032

Alagiakrishnan K, Halverson T. Microbial therapeutics in neurocognitive and psychiatric disorders. J Clin Med Res. 2021 Sep;13(9):439-59. DOI: 10.14740/jocmr4575

Dimidi E, Christodoulides S, Scott SM, Whelan K. Mechanisms of action of probiotics and the gastrointestinal microbiota on gut motility and constipation. Adv Nutr. 2017 May 15;8(3):484-94. DOI: 10.3945/an.116.014407

Khodamoradi Y, Kessel J, Vehreschild JJ, Vehreschild MJGT. The role of microbiota in preventing multidrug-resistant bacterial infections. Dtsch Arztebl Int. 2019 Oct 4;116(40):670-6. DOI: 10.3238/arztebl.2019.0670

Kerry RG, Patra JK, Gouda S, Park Y, Shin HS, Das G. Benefaction of probiotics for human health: A review. J Food Drug Anal. 2018 Jul;26(3):927-39. DOI: 10.1016/j.jfda.2018.01.002

Fariq A, Saeed A. Production and biomedical applications of probiotic biosurfactants. Curr Microbiol. 2016 Apr;72(4):489-95. DOI: 10.1007/s00284-015-0978-4

Ibrahim SA, Gyawali R, Awaisheh SS, Ayivi RD, Silva RC, Subedi K, et al. Fermented foods and probiotics: an approach to lactose intolerance. J Dairy Res. 2021 Aug;88(3):357-65. DOI: 10.1017/S0022029921000625

Kelly CP, Chong Nguyen C, Palmieri LJ, Pallav K, Dowd SE, Humbert L, et al. Saccharomyces boulardii CNCM I-745 modulates the fecal bile acids metabolism during antimicrobial therapy in healthy volunteers. Front Microbiol. 2019 Mar 4;10:336. DOI: 10.3389/fmicb.2019.00336

Mekonnen SA, Merenstein D, Fraser CM, Marco ML. Molecular mechanisms of probiotic prevention of antibiotic-associated diarrhea. Curr Opin Biotechnol. 2020 Feb;61:226-34. DOI: 10.1016/j.copbio.2020.01.005

Choi CH, Jo SY, Park HJ, Chang SK, Byeon JS, Myung SJ. A randomized, double-blind, placebo-controlled multicenter trial of Saccharomyces boulardii in irritable bowel syndrome: effect on quality of life. J Clin Gastroenterol. 2011 Sep;45(8):679-83. DOI: 10.1097/MCG.0b013e318204593e

Ten Bruggencate SJ, Girard SA, Floris-Vollenbroek EG, Bhardwaj R, Tompkins TA. The effect of a multi-strain probiotic on the resistance toward Escherichia coli challenge in a randomized, placebo-controlled, double-blind intervention study. Eur J Clin Nutr. 2015 Mar;69(3):385-91. DOI: 10.1038/ejcn.2014.238

Champié I, Rousseau G. Probiotic formula. Nutrafoods. 2011;10(1):13-7. DOI: 10.1007/bf03223350

De Wolfe TJ, Eggers S, Barker AK, Kates AE, Dill-McFarland KA, Suen G, et al. Oral probiotic combination of Lactobacillus and Bifidobacterium alters the gastrointestinal microbiota during antibiotic treatment for Clostridium difficile infection. PLoS One. 2018 Sep 28;13(9):e0204253. DOI: 10.1371/journal.pone.0204253

Saavedra JM, Abi-Hanna A, Moore N, Yolken RH. Long-term consumption of infant formulas containing live probiotic bacteria: tolerance and safety. Am J Clin Nutr. 2004 Feb;79(2):261-7. DOI: 10.1093/ajcn/79.2.261

Ringel-Kulka T, Palsson OS, Maier D, Carroll I, Galanko JA, Leyer G, et al. Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders: a double-blind study. J Clin Gastroenterol. 2011 Jul;45(6):518-25. DOI: 10.1097/MCG.0b013e31820ca4d6

Oak SJ, Jha R. The effects of probiotics in lactose intolerance: a systematic review. Crit Rev Food Sci Nutr. 2019;59(11):1675-83. DOI: 10.1080/10408398.2018.1425977

Fung WY, Lye HS, Lim TJ, Kuan CY, Liong MT. Roles of probiotic on gut health. In: Liong MT, editor. Probiotics. Microbiology monographs, vol 21. Berlin, Heidelberg: Springer Berlin Heidelberg; 2011. p. 139-65. DOI: 10.1007/978-3-642-20838-6_6

Savitri, Lata P. Probiotics for human health. In: Goel G, Kumar A, editors. Microorganisms for sustainability. Singapore: Springer Singapore; 2020. p. 181-212. DOI: 10.1007/978-981-15-6795-7_8

Kruis W. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut. 2004 Nov 1;53(11):1617-23. DOI: 10.1136/gut.2003.037747

McFarland LV. Evidence-based review of probiotics for antibiotic-associated diarrhea and Clostridium difficile infections. Anaerobe. 2009 Dec;15(6):274-80. DOI: 10.1016/j.anaerobe.2009.09.002

Vandenplas Y, Huys G, Daube G. Probiotics: an update. J Pediatr (Rio J). 2015 Jan-Feb;91(1):6-21. DOI: 10.1016/j.jped.2014.08.005

Manfredi M, Bizzarri B, Sacchero RI, Maccari S, Calabrese L, Fabbian F, et al. Helicobacter pylori infection in clinical practice: probiotics and a combination of probiotics + lactoferrin improve compliance, but not eradication, in sequential therapy. Helicobacter. 2012 Aug;17(4):254-63. DOI: 10.1111/j.1523-5378.2012.00944.x

Emara MH, Mohamed SY, Abdel-Aziz HR. Lactobacillus reuteri in management of Helicobacter pylori infection in dyspeptic patients: a double-blind placebo-controlled randomized clinical trial. Therap Adv Gastroenterol. 2014 Jan;7(1):4-13. DOI: 10.1177/1756283X13503514

Panduru M, Panduru NM, Sălăvăstru CM, Tiplica GS. Probiotics and primary prevention of atopic dermatitis: a meta-analysis of randomized controlled studies. J Eur Acad Dermatol Venereol. 2015 Feb;29(2):232-42. DOI: 10.1111/jdv.12496

Morita H, He F, Kawase M, Kubota A, Hiramatsu M, Kurisaki JI, et al. Preliminary human study for possible alteration of serum immunoglobulin E production in perennial allergic rhinitis with fermented milk prepared with Lactobacillus gasseri TMC0356. Microbiol Immunol. 2006;50(9):701-6. DOI: 10.1111/j.1348-0421.2006.tb03842.x

Ishida Y, Nakamura F, Kanzato H, Sawada D, Hirata H, Nishimura A, et al. Clinical effects of Lactobacillus acidophilus strain L-92 on perennial allergic rhinitis: a double-blind, placebo-controlled study. J Dairy Sci. 2005 Feb;88(2):527-33. DOI: 10.3168/jds.S0022-0302(05)72714-4

Crovesy L, Gonçalves DC, Trigo EL. Probiotics in allergy treatment: a literature review. Rev Esp Nutr Hum Diet. 2017;21(3):293-9. DOI: 10.14306/renhyd.21.3.361

Bickert T, Trujillo-Vargas CM, Duechs M, Wohlleben G, Polte T, Hansen G, et al. Probiotic Escherichia coli Nissle 1917 suppresses allergen-induced Th2 responses in the airways. Int Arch Allergy Immunol. 2009;149(3):219-30. DOI: 10.1159/000199717

Zhang B, An J, Shimada T, Liu S, Maeyama K. Oral administration of Enterococcus faecalis FK-23 suppresses Th17 cell development and attenuates allergic airway responses in mice. Int J Mol Med. 2012 Aug;30(2):248-54. DOI: 10.3892/ijmm.2012.1010

Alexandre Y, Le Blay G, Boisramé-Gastrin S, Le Gall F, Héry-Arnaud G, Gouriou S, et al. Probiotics: a new way to fight bacterial pulmonary infections? Med Mal Infect. 2014 Jan;44(1):9-17. DOI: 10.1016/j.medmal.2013.05.001

Liu X, Cao S, Zhang X. Modulation of gut microbiota-brain axis by probiotics, prebiotics, and diet. J Agric Food Chem. 2015 Sep 16;63(36):7885-95. DOI: 10.1021/acs.jafc.5b02404

Kałużna-Czaplińska J, Błaszczyk S. The level of arabinitol in autistic children after probiotic therapy. Nutrition. 2012 Feb;28(2):124-6. DOI: 10.1016/j.nut.2011.08.002

Lavasani S, Dzhambazov B, Nouri M, Fåk F, Buske S, Molin G, et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One. 2010 Feb 2;5(2):e9009. DOI: 10.1371/journal.pone.0009009

Lunia MK, Sharma BC, Sharma P, Sachdeva S, Srivastava S. Probiotics prevent hepatic encephalopathy in patients with cirrhosis: a randomized controlled trial. Clin Gastroenterol Hepatol. 2014 Jun;12(6):1003-8.e1. DOI: 10.1016/j.cgh.2013.11.006

Homayouni A, Bastani P, Ziyadi S, Mohammad-Alizadeh-Charandabi S, Ghalibaf M, Mortazavian AM, et al. Effects of probiotics on the recurrence of bacterial vaginosis: a review. J Low Genit Tract Dis. 2014 Jan;18(1):79-86. DOI: 10.1097/LGT.0b013e31829156ec

Mazloom K, Siddiqi I, Covasa M. Probiotics: how effective are they in the fight against obesity? Nutrients. 2019 Jan 24;11(2):258. DOI: 10.3390/nu11020258

Kumar M, Nagpal R, Kumar R, Hemalatha R, Verma V, Kumar A, et al. Holesterol-lowering probiotics as potential biotherapeutics for metabolic diseases. Exp Diabetes Res. 2012;2012:902917. DOI: 10.1155/2012/902917

Shimauchi H, Mayanagi G, Nakaya S, Minamibuchi M, Ito Y, Yamaki K, et al. Improvement of periodontal condition by probiotics with Lactobacillus salivarius WB21: a randomized, double-blind, placebo-controlled study. J Clin Periodontol. 2008 Oct;35(10):897-905. DOI: 10.1111/j.1600-051X.2008.01306.x

Seminario-Amez M, Lopez-Lopez J, Estrugo-Devesa A, Ayuso-Montero R, Jane-Salas E. Probiotics and oral health: a systematic review. Med Oral Patol Oral Cir Bucal. 2017 May 1;22(3):e282-8. DOI: 10.4317/medoral.21494

Hatakka K, Ahola AJ, Yli-Knuuttila H, Richardson M, Poussa T, Meurman JH, et al. Probiotics reduce the prevalence of oral candida in the elderly—a randomized controlled trial. J Dent Res. 2007 Feb;86(2):125-30. DOI: 10.1177/154405910708600204

Tsigalou C, Stavropoulou E, Bezirtzoglou E. Current Insights in microbiome shifts in Sjogren's syndrome and possible therapeutic interventions. Front Immunol. 2018 May 24;9:1106. DOI: 10.3389/fimmu.2018.01106

Sales-Campos H, Soares SC, Oliveira CJF. An introduction of the role of probiotics in human infections and autoimmune diseases. Crit Rev Microbiol. 2019 Aug;45(4):413-32. DOI: 10.1080/1040841X.2019.1621261

Guo X, Yang X, Li Q, Shen X, Zhong H, Yang Y. The microbiota in systemic lupus erythematosus: an update on the potential function of probiotics. Front Pharmacol. 2021 Nov 23;12:759095. DOI: 10.3389/fphar.2021.759095

Lei WT, Shih PC, Liu SJ, Lin CY, Yeh TL 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):1175. DOI: 10.3390/nu9111175

El Hage R, Hernandez-Sanabria E, Van de Wiele T. Emerging trends in "smart probiotics": functional consideration for the development of novel health and industrial applications. Front Microbiol. 2017 Sep 29;8:1889. DOI: 10.3389/fmicb.2017.01889

de Vos WM. Microbe profile: Akkermansia muciniphila: a conserved intestinal symbiont that acts as the gatekeeper of our mucosa. Microbiology (Reading). 2017 May;163(5):646-8. DOI: 10.1099/mic.0.000444

Morovic W, Budinoff CR. Epigenetics: a new frontier in probiotic research. Trends Microbiol. 2021 Feb;29(2):117-26. DOI: 10.1016/j.tim.2020.04.008

Jain S, Chatterjee A, Panwar S, Yadav AK, Majumdar RS, Kumar A. Metabolic engineering approaches for improvement of probiotics functionality. In: Goel G, Kumar A, editors. Microorganisms for sustainability. Singapore: Springer Singapore; 2020. p. 225-40. DOI: 10.1007/978-981-15-6795-7_10

Kanadje AP, Banerjee UC. Designing probiotics and its clinical applications. In: Pawar SV, Rishi P, editors. Probiotic research in therapeutics. Singapore: Springer Singapore; 2021. p. 231-51. DOI: 10.1007/978-981-33-6236-9_10

Sola-Oladokun B, Culligan EP, Sleator RD. Engineered probiotics: applications and biological containment. Annu Rev Food Sci Technol. 2017 Feb 28;8:353-70. DOI: 10.1146/annurev-food-030216-030256

Bravo D, Landete JM. Genetic engineering as a powerful tool to improve probiotic strains. Biotechnol Genet Eng Rev. 2017 Oct;33(2):173-89. DOI: 10.1080/02648725.2017.1408257

Wu J, Xin Y, Kong J, Guo T. Genetic tools for the development of recombinant lactic acid bacteria. Microb Cell Fact. 2021 Jun 19;20(1):118. DOI: 10.1186/s12934-021-01607-1

Bober JR, Beisel CL, Nair NU. Synthetic biology approaches to engineer probiotics and members of the human microbiota for biomedical applications. Annu Rev Biomed Eng. 2018 Jun 4;20(1):277-300. DOI: 10.1146/annurev-bioeng-062117-121019

Börner RA, Kandasamy V, Axelsen AM, Nielsen AT, Bosma EF. Genome editing of lactic acid bacteria: opportunities for food, feed, pharma and biotech. FEMS Microbiol Lett. 2019 Jan 1;366(1):fny291. DOI: 10.1093/femsle/fny291

Plavec TV, Berlec A. Safety aspects of genetically modified lactic acid bacteria. Microorganisms. 2020 Feb 21;8(2):297. DOI: 10.3390/microorganisms8020297

Akçelik M, Akçelik N, Şanlıbaba P, Uymaz Tezel B. Genetic modification and sequence analysis of probiotic microorganisms. In: Dhanasekaran D, Sankaranarayanan A, editors. Advances in probiotics. Academic Press; 2021. p. 101-12. DOI: 10.1016/b978-0-12-822909-5.00006-x

Landete JM. A review of food-grade vectors in lactic acid bacteria: from the laboratory to their application. Crit Rev Biotechnol. 2017 May;37(3):296-308. DOI: 10.3109/07388551.2016.1144044

Papagianni M. Metabolic engineering of lactic acid bacteria for the production of industrially important compounds. Comput Struct Biotechnol J. 2012 Oct 29;3(4):e201210003. DOI: 10.5936/csbj.201210003

Almalki MA. Production of medically important lactic acid by lactobacillus pentosus: a biological conversion method. Indian J Sci Technol. 2016 Jan 9;9(4). DOI: 10.17485/ijst/2016/v9i4/84143

Steidler L, Neirynck S, Huyghebaert N, Snoeck V, Vermeire A, Goddeeris B, et al. Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nat Biotechnol. 2003 Jul;21(7):785-9. DOI: 10.1038/nbt840

Martín MC, Pant N, Ladero V, Günaydın G, Andersen KK, Álvarez B, et al. Integrative expression system for delivery of antibody fragments by lactobacilli. Appl Environ Microbiol. 2011 Mar;77(6):2174-9. DOI: 10.1128/AEM.02690-10

van Tilburg AY, Cao H, van der Meulen SB, Solopova A, Kuipers OP. Metabolic engineering and synthetic biology employing Lactococcus lactis and Bacillus subtilis cell factories. Curr Opin Biotechnol. 2019 Oct;59:1-7. DOI: 10.1016/j.copbio.2019.01.007

Sorokulova I. Recombinant probiotics: future perspectives in disease treatment. J Probiotics Health. 2014;2(2):1000e109. DOI: 10.4172/2329-8901.1000e109

Mazhar SF, Afzal M, Almatroudi A, Munir S, Ashfaq UA, Rasool M, et al. The prospects for the therapeutic implications of genetically engineered probiotics. J Food Qual. 2020 Apr 7;2020:1-11. DOI: 10.1155/2020/9676452

Barra M, Danino T, Garrido D. Engineered probiotics for detection and treatment of inflammatory intestinal diseases. Front Bioeng Biotechnol. 2020 Mar 31;8:265. DOI: 10.3389/fbioe.2020.00265

Carvalho RD, do Carmo FL, de Oliveira Junior A, Langella P, Chatel JM, Bermúdez-Humarán LG, et al. Use of wild type or recombinant lactic acid bacteria as an alternative treatment for gastrointestinal inflammatory diseases: a focus on inflammatory bowel diseases and mucositis. Front Microbiol. 2017 May 9;8:800. DOI: 10.3389/fmicb.2017.00800

Rochat T, Miyoshi A, Gratadoux JJ, Duwat P, Sourice S, Azevedo V, et al. High-level resistance to oxidative stress in Lactococcus lactis conferred by Bacillus subtilis catalase KatE. Microbiology (Reading). 2005 Sep;151(Pt 9):3011-8. DOI: 10.1099/mic.0.27861-0

Rochat T, Bermúdez-Humarán L, Gratadoux JJ, Fourage C, Hoebler C, Corthier G, et al. Anti-inflammatory effects of Lactobacillus casei BL23 producing or not a manganese-dependant catalase on DSS-induced colitis in mice. Microb Cell Fact. 2007 Jul 20;6(1):22. DOI: 10.1186/1475-2859-6-22

Sanders JW, Leenhouts KJ, Haandrikman AJ, Venema G, Kok J. Stress response in lactococcus lactis: cloning, expression analysis, and mutation of the lactococcal superoxide dismutase gene. J Bacteriol. 1995 Sep;177(18):5254-60. DOI: 10.1128/jb.177.18.5254-5260.1995

He JY, Wang WZ, Qi HZ, Ma Y, He SY. Use of recombinant Lactobacillus sakei for the prevention and treatment of radiation-induced enteritis. Med Hypotheses. 2018 Oct;119:37-40. DOI: 10.1016/j.mehy.2018.07.024

Breyner NM, Vilas Boas PB, Fernandes G, de Carvalho RD, Rochat T, Michel ML, et al. Oral delivery of pancreatitis-associated protein by Lactococcus lactis displays protective effects in dinitro-benzenesulfonic-acid-induced colitis model and is able to modulate the composition of the microbiota. Environ Microbiol. 2019 Nov;21(11):4020-31. DOI: 10.1111/1462-2920.14748

Carvalho R, Vaz A, Pereira FL, Dorella F, Aguiar E, Chatel JM, et al. Gut microbiome modulation during treatment of mucositis with the dairy bacterium Lactococcus lactis and recombinant strain secreting human antimicrobial PAP Sci Rep. 2018 Oct 10;8(1):15072. DOI: 10.1038/s41598-018-33469-w

Qiu ZB, Chen J, Chen JJ, Rong L, Ding WQ, Yang HJ, et al. Effect of recombinant Lactobacillus casei expressing interleukin-10 in dextran sulfate sodium-induced colitis mice. J Dig Dis. 2013 Feb;14(2):76-83. DOI: 10.1111/1751-2980.12006

Hong N, Ku S, Yuk K, Johnston TV, Ji GE, Park MS. Production of biologically active human interleukin-10 by Bifidobacterium bifidum BGN4. Microb Cell Fact. 2021 Jan 19;20(1):16. DOI: 10.1186/s12934-020-01505-y

Li J, Yu S, Pan X, Zhang M, Lv Z, Pan LL, Sun J. Recombinant CRAMP-producing Lactococcus lactis attenuates dextran sulfate sodium-induced colitis by colonic colonization and inhibiting p38/NF-κB signaling. Food Nutr Res. 2021 Sep 28;65. DOI: 10.29219/fnr.v65.5570

Gardlik R, Palffy R, Celec P. Recombinant probiotic therapy in experimental colitis in mice. Folia Biol (Praha). 2012;58(6):238-45.

Focareta A, Paton JC, Morona R, Cook J, Paton AW. A recombinant probiotic for treatment and prevention of cholera. Gastroenterology. 2006 May;130(6):1688-95. DOI: 10.1053/j.gastro.2006.02.005

Duan F, March JC Interrupting Vibrio cholerae infection of human epithelial cells with engineered commensal bacterial signaling. Biotechnol Bioeng. 2008 Sep 1;101(1):128-34. DOI: 10.1002/bit.21897

Duan F, March JC. Engineered bacterial communication prevents Vibrio cholerae virulence in an infant mouse model. Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11260-4. DOI: 10.1073/pnas.1001294107

Kokai-Kun JF, Chanturiya T, Mond JJ. Lysostaphin as a treatment for systemic Staphylococcus aureus infection in a mouse model. J Antimicrob Chemother. 2007 Nov;60(5):1051-9. DOI: 10.1093/jac/dkm347

Pipiya SO, Mokrushina YA, Gabibov AG, Smirnov IV, Terekhov SS. Selective eradication of Staphylococcus aureus by the designer genetically programmed yeast biocontrol agent. Antibiotics (Basel). 2020 Aug 19;9(9):527. DOI: 10.3390/antibiotics9090527

El-Chami C, Choudhury R, Mohammedsaeed W, McBain AJ, Kainulainen V, Lebeer et al. Multiple Proteins of Lacticaseibacillus rhamnosus GG Are Involved in the protection of keratinocytes from the toxic effects of Staphylococcus aureus. Front Microbiol. 2022 May 11;13:875542. DOI: 10.3389/fmicb.2022.875542

Cruz KC, Enekegho LO, Stuart DT. Bioengineered probiotics: synthetic biology can provide live cell therapeutics for the treatment of foodborne diseases. Front Bioeng Biotechnol. 2022 May 17;10:890479. DOI: 10.3389/fbioe.2022.890479

Vedantam G, Kochanowsky J, Lindsey J, Mallozzi M, Roxas JL, Adamson C, et al. An engineered synthetic biologic protects against Clostridium difficile infection. Front Microbiol. 2018 Sep 5;9:2080. DOI: 10.3389/fmicb.2018.02080

Paton AW, Jennings MP, Morona R, Wang H, Focareta A, Roddam LF, et al. Recombinant probiotics for treatment and prevention of enterotoxigenic Escherichia coli diarrhea. Gastroenterology. 2005 May;128(5):1219-28. DOI: 10.1053/j.gastro.2005.01.050

Koo OK, Amalaradjou MA, Bhunia AK. Recombinant probiotic expressing Listeria adhesion protein attenuates Listeria monocytogenes virulence in vitro. PLoS One. 2012;7(1):e29277. DOI: 10.1371/journal.pone.0029277

Potebnia HP, Safronova LA, Cheremshenko NL, Lisovenko HS, Sorokulova IB, Prykhod'ko VO, et al. Influence of probiotic subalin on efficiency of antitumor vaccine. Mikrobiol Z. 2006 Nov-Dec;68(6):51-8.

Starovoitova SА. Probiotics based on transgenic microorganisms. Biotechnologia Acta. 2013;6(1):34-45.

Choi HJ, Ahn JH, Park SH, Do KH, Kim J, Moon Y. Enhanced wound healing by recombinant Escherichia coli Nissle 1917 via human epidermal growth factor receptor in human intestinal epithelial cells: therapeutic implication using recombinant probiotics. Infect Immun. 2012 Mar;80(3):1079-87. DOI: 10.1128/IAI.05820-11

Yuan S, Dong M, Zhang H, Xu H, Wang Q, Yan C, et al. Oral delivery of a Lactococcus lactis expressing extracellular TGFβR2 alleviates hepatic fibrosis. Appl Microbiol Biotechnol. 2021 Aug;105(14-15):6007-18. DOI: 10.1007/s00253-021-11485-7

Lee J, Arun Kumar S, Jhan YY, Bishop CJ. Engineering DNA vaccines against infectious diseases. Acta Biomater. 2018 Oct 15;80:31-47. DOI: 10.1016/j.actbio.2018.08.033

Qiao N, Du G, Zhong X, Sun X. Recombinant lactic acid bacteria as promising vectors for mucosal vaccination. Exploration. 2021 Oct;1(2):20210026. DOI: 10.1002/EXP.20210026

Mezhenskaya D, Isakova-Sivak I, Gupalova T, Bormotova E, Kuleshevich E, Kramskaya T, et al. A live probiotic vaccine prototype based on conserved influenza a virus antigens protect mice against lethal influenza virus infection. Biomedicines. 2021 Oct 21;9(11):1515. DOI: 10.3390/biomedicines9111515

Desheva Y, Leontieva G, Kramskaya T, Gupalova T, Losev I, Kuleshevich E, et al. Developing a live probiotic vaccine based on the Enterococcus faecium L3 strain expressing Influenza neuraminidase. Microorganisms. 2021 Nov 27;9(12):2446. DOI: 10.3390/microorganisms9122446

Niu H, Xing JH, Zou BS, Shi CW, Huang HB, Jiang YL, et al. Immune evaluation of recombinant Lactobacillus plantarum with surface display of HA1-DCpep in mice. Front Immunol. 2021 Dec 1;12:800965. DOI: 10.3389/fimmu.2021.800965

Afchangi A, Latifi T, Jalilvand S, Marashi SM, Shoja Z. Combined use of lactic-acid-producing bacteria as probiotics and rotavirus vaccine candidates expressing virus-specific proteins. Arch Virol. 2021 Apr;166(4):995-1006. DOI: 10.1007/s00705-021-04964-9

Shonyela SM, Shi C, Yang W, Cao X, Yang G, Wang C. Recombinant Lactobacillus plantarum NC8 strain expressing porcine rotavirus VP7 induces specific antibodies in BALB/c mice. Acta Biochim Biophys Sin (Shanghai). 2021 May 21;53(6):707-18. DOI: 10.1093/abbs/gmab050

Wang J, Jiang H, Yang R, Zhang S, Zhao W, Hu J, et al. Construction and evaluation of recombinant Lactobacillus plantarum NC8 delivering one single or two copies of G protein fused with a DC-targeting peptide (DCpep) as novel oral rabies vaccine. Vet Microbiol. 2020 Dec;251:108906. DOI: 10.1016/j.vetmic.2020.108906

Moradi-kalbolandi S, Majidzadeh-A K, Abdolvahab MH, Jalili N, Farahmand L. The role of mucosal immunity and recombinant probiotics in SARS-CoV2 vaccine development. Probiotics Antimicrob Proteins. 2021 Oct;13(5):1239-53. DOI: 10.1007/s12602-021-09773-9

Taghinezhad-S S, Mohseni AH, Bermúdez-Humarán LG, Casolaro V, Cortes-Perez NG, Keyvani H, et al. Probiotic-Based vaccines may provide effective protection against COVID-19 acute respiratory disease. Vaccines (Basel). 2021 May 6;9(5):466. DOI: 10.3390/vaccines9050466

Zhang L, Yao L, Guo Y, Li X, Ma L, Sun R, et al. Oral SARS-CoV-2 spike protein recombinant yeast candidate prompts specific antibody and gut microbiota reconstruction in mice. Front Microbiol. 2022 Apr 7;13:792532. DOI: 10.3389/fmicb.2022.792532

Amalaradjou MA, Bhunia AK. Bioengineered probiotics, a strategic approach to control enteric infections. Bioengineered. 2013 Nov-Dec;4(6):379-87. DOI: 10.4161/bioe.23574

Lin R, Zhang Y, Long B, Li Y, Wu Y, Duan S, et al. Oral immunization with recombinant Lactobacillus acidophilus expressing espA-Tir-M confers protection against enterohemorrhagic Escherichia coli O157:H7 challenge in mice. Front Microbiol. 2017 Mar 15;8:417. DOI: 10.3389/fmicb.2017.00417

Diaz-Dinamarca DA, Hernandez C, Escobar DF, Soto DA, Muñoz GA, Badilla JF, et al. Mucosal vaccination with Lactococcus lactis-secreting surface immunological protein induces humoral and cellular immune protection against group b Streptococcus in a murine model. Vaccines (Basel). 2020 Mar 26;8(2):146. DOI: 10.3390/vaccines8020146

Mohammadi E, Golchin M. High protection of mice against Brucella abortus by oral immunization with recombinant probiotic Lactobacillus casei vector vaccine, expressing the outer membrane protein OMP19 of Brucella species. Comp Immunol Microbiol Infect Dis. 2020 Jun;70:101470. DOI: 10.1016/j.cimid.2020.101470

Shirdast H, Ebrahimzadeh F, Taromchi AH, Mortazavi Y, Esmaeilzadeh A, Sekhavati MH, et al. Recombinant Lactococcus Lactis displaying Omp31 antigen of Brucella melitensis can induce an immunogenic response in BALB/c mice. Probiotics Antimicrob Proteins. 2021 Feb;13(1):80-9. DOI: 10.1007/s12602-020-09684-1

Kajikawa A, Igimi S. Development of recombinant vaccines in Lactobacilli for elimination of Salmonella. Biosci Microflora. 2011;30(4):93-8. DOI: 10.12938/bifidus.30.93

Awad S, Al-Ahmer S, Salih S. Expression in Saccharomyces boulardii of recombinant toxin-coregulated pilus A subunit (TcpA) of Vibrio cholerae O1. VacciMonitor. 2020;29(3):136-42.

Alimolaei M, Golchin M, Abshenas J, Ezatkhah M, Bafti MS. A recombinant probiotic, Lactobacillus casei, expressing the Clostridium perfringens α-toxoid, as an orally vaccine candidate against gas gangrene and necrotic enteritis. Probiotics Antimicrob Proteins. 2018 Jun;10(2):251-7. DOI: 10.1007/s12602-017-9276-8

Ding G, Bai J, Feng B, Wang L, Qiao X, Zhou H, et al. An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ε, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity. Virulence. 2019 Dec;10(1):754-67. DOI: 10.1080/21505594.2019.1653720

Xue Y, Zhang B, Wang N, Huang HB, Quan Y, Lu HN, et al. Oral vaccination of mice with Trichinella spiralis putative serine protease and murine interleukin-4 DNA delivered by invasive Lactiplantibacillus plantarum elicits protective immunity. Front Microbiol. 2022 May 3;13:859243. DOI: 10.3389/fmicb.2022.859243

Wang D, Liu Q, Jiang YL, Huang HB, Li JY, Pan TX, et al. Oral immunization with recombinant Lactobacillus plantarum expressing Nudix hydrolase and 43 kDa proteins confers protection against Trichinella spiralis in BALB/c mice. Acta Trop. 2021 Aug;220:105947. DOI: 10.1016/j.actatropica.2021.105947

Lin J, Mou C, Zhang S, Zhu L, Li Y, Yang Q. Immune responses induced by recombinant Bacillus subtilis expressing the PEDV spike protein targeted at microfold cells. Vet Sci. 2022 Apr 25;9(5):211. DOI: 10.3390/vetsci9050211

Yigang XU, Yijing LI. Construction of recombinant Lactobacillus casei efficiently surface displayed and secreted porcine parvovirus VP2 protein and comparison of the immune responses induced by oral immunization. Immunology. 2008 May;124(1):68-75. DOI: 10.1111/j.1365-2567.2007.02738.x

Jin YB, Yang WT, Shi CW, Feng B, Huang KY, Zhao GX, et al. Immune responses induced by recombinant Lactobacillus plantarum expressing the spike protein derived from transmissible gastroenteritis virus in piglets. Appl Microbiol Biotechnol. 2018 Oct;102(19):8403-17. DOI: 10.1007/s00253-018-9205-0

Huang Q, Niu T, Zou B, Wang J, Xin J, Niu H, et al. Lactobacillus plantarum surface-displayed ASFV (p14.5] can stimulate immune responses in mice. Vaccines (Basel). 2022 Feb 24;10(3):355. DOI: 10.3390/vaccines10030355

Ou B, Jiang B, Jin D, Yang Y, Zhang M, Zhang D, et al. Engineered recombinant Escherichia coli probiotic strains integrated with F4 and F18 fimbriae cluster genes in the chromosome and their assessment of immunogenic efficacy in vivo. ACS Synth Biol. 2020 Feb 21;9(2):412-26. DOI: 10.1021/acssynbio.9b00430

Muñoz C, González-Lorca J, Parra M, Soto S, Valdes N, Sandino AM, et al. Lactococcus lactis expressing type I interferon from atlantic salmon enhances the innate antiviral immune response in vivo and in vitro. Front Immunol. 2021 Aug 12;12:696781. DOI: 10.3389/fimmu.2021.696781

Ryan PM, Patterson E, Kent RM, Stack H, O’Connor PM, Murphy K, et al. Recombinant incretin-secreting microbe improves metabolic dysfunction in high-fat diet fed rodents. Sci Rep. 2017 Oct 19;7(1):13523. DOI: 10.1038/s41598-017-14010-x

Dosoky NS, Chen Z, Guo Y, McMillan C, Flynn CR, Davies SS. Two-week administration of engineered Escherichia coli establishes persistent resistance to diet-induced obesity even without antibiotic pre-treatment. Appl Microbiol Biotechnol. 2019 Aug;103(16):6711-23. DOI: 10.1007/s00253-019-09958-x

Cao WY, Dong M, Hu ZY, Wu J, Li YC, Xu HD. Recombinant Lactococcus lactis NZ3900 expressing bioactive human FGF21 reduced body weight of Db/Db mice through the activity of brown adipose tissue. Benef Microbes. 2020 Feb 19;11(1):67-78. DOI: 10.3920/BM2019.0093

Oh JH, Schueler KL, Stapleton DS, Alexander LM, Yen CL, Keller MP, et al. Secretion of recombinant interleukin-22 by engineered lactobacillus reuteri reduces fatty liver disease in a mouse model of diet-induced obesity. mSphere. 2020 Jun 24;5(3):e00183-20. DOI: 10.1128/mSphere.00183-20

Sun Z, Sun X, Li J, Li Z, Hu Q, Li L, et al. Using probiotics for type 2 diabetes mellitus intervention: advances, questions, and potential. Crit Rev Food Sci Nutr. 2020;60(4):670-83. DOI: 10.1080/10408398.2018.1547268

Lin Y, Krogh-Andersen K, Pelletier J, Marcotte H, Östenson CG, Hammarström L. Oral delivery of pentameric glucagon-like peptide-1 by recombinant lactobacillus in diabetic rats. PLoS One. 2016 Sep 9;11(9):e0162733. DOI: 10.1371/journal.pone.0162733

Ma Y, Liu J, Hou J, Dong Y, Lu Y, Jin L, et al. Oral administration of recombinant Lactococcus lactis expressing HSP65 and tandemly repeated P277 reduces the incidence of type I diabetes in non-obese diabetic mice. PLoS One. 2014 Aug 26;9(8):e105701. DOI: 10.1371/journal.pone.0105701

Verma A, Xu K, Du T, Zhu P, Liang Z, Liao S, et al. Expression of human ACE2 in Lactobacillus and beneficial effects in diabetic retinopathy in mice. Mol Ther Methods Clin Dev. 2019 Jul 10;14:161-70. DOI: 10.1016/j.omtm.2019.06.007

Verma A, Zhu P, Xu K, Du T, Liao S, Liang Z, et al. Angiotensin-[1–7] expressed from Lactobacillus bacteria protect diabetic retina in mice. Transl Vis Sci Technol. 2020 Dec 14;9(13):20. DOI: 10.1167/tvst.9.13.20

Ramírez AM, Rodriguez-López A, Ardila A, Beltran L, Patarroyo CA, Melendez AD, et al. Production of human recombinant phenylalanine hydroxylase in Lactobacillus plantarum for gastrointestinal delivery. Eur J Pharm Sci. 2017 Nov 15;109:48-55. DOI: 10.1016/j.ejps.2017.07.033

Durrer KE, Allen MS, Hunt von Herbing I. Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU. PLoS One. 2017 May 17;12(5):e0176286. DOI: 10.1371/journal.pone.0176286

Wang G, Hao M, Liu Q, Jiang Y, Huang H, Yang G, et al. Protective effect of recombinant Lactobacillus plantarum against H2O2-induced oxidative stress in HUVEC cells. J Zhejiang Univ Sci B. 2021 May 15;22(5):348-65. DOI: 10.1631/jzus.B2000441

Petrarca C, Carpiniello F, Di Gioacchino M. Recombinant probiotics for allergen immunotherapy. Int J Vaccines Vaccin. 2015;1(3):00017. DOI: 10.15406/ijvv.2015.01.00017

Jaworska K, Koper M, Ufnal M. Gut microbiota and renin-angiotensin system: a complex interplay at local and systemic levels. Am J Physiol Gastrointest Liver Physiol. 2021 Oct 1;321(4):355-66. DOI: 10.1152/ajpgi.00099.2021

Charng Y, Lin C, Hsu C. Inhibition of allergen-induced airway inflammation and hyperreactivity by recombinant lactic-acid bacteria. Vaccine. 2006 Aug 14;24(33-34):5931-6. DOI: 10.1016/j.vaccine.2005.07.107

Rigaux P, Daniel C, Hisbergues M, Muraille E, Hols P, Pot B, et al. Immunomodulatory properties ofLactobacillus plantarumand its use as a recombinant vaccine against mite allergy. Allergy. 2009 Mar;64(3):406-14. DOI: 10.1111/j.1398-9995.2008.01825.x

Adam E, Delbrassinne L, Bouillot C, Reynders V, Mailleux AC, Muraille E, et al. Probiotic Escherichia coli Nissle 1917 activates DC and prevents house dust mite allergy through a TLR4-dependent pathway. Eur J Immunol. 2010 Jul;40(7):1995-2005. DOI: 10.1002/eji.200939913

Ai C, Zhang Q, Ren C, Wang G, Liu X, Tian F, et al. Genetically engineered Lactococcus lactis protect against house dust mite allergy in a balb/c mouse model. PLoS One. 2014 Oct 7;9(10):e109461. DOI: 10.1371/journal.pone.0109461

Moussu H, Van Overtvelt L, Horiot S, Tourdot S, Airouche S, Zuercher A, et al. Bifidobacterium bifidum NCC 453 promotes tolerance induction in murine models of sublingual immunotherapy. Int Arch Allergy Immunol. 2012;158(1):35-42. DOI: 10.1159/000330101

Schabussova I, Hufnagl K, Tang ML, Hoflehner E, Wagner A, Loupal G, et al. Perinatal maternal administration of lactobacillus paracasei NCC 2461 prevents allergic inflammation in a mouse model of birch pollen allergy. PLoS One. 2012;7(7):e40271. DOI: 10.1371/journal.pone.0040271

Daniel C, Repa A, Wild C, Pollak A, Pot B, Breiteneder H, et al. Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1. Allergy. 2006 Jul;61(7):812-9. DOI: 10.1111/j.1398-9995.2006.01071.x

Nasiraie LR, Tabatabaie F, Sankian M, Shahidi F, Varasteh A. Construction of a recombinant allergen-producing probiotic bacterial strain: Introduction of a new line for a live oral vaccine against Chenopodium album pollen allergy. Rep Biochem Mol Biol. 2013 Oct;2(1):16-27.

Vasiee A, Falah F, Sankian M, Tabatabaei-Yazdi F, Mortazavi SA. Oral immunotherapy using probiotic ice cream containing recombinant food-grade Lactococcus lactis which inhibited allergic responses in a BALB/c mouse model. J Immunol Res. 2020 Sep 24;2020:2635230. DOI: 10.1155/2020/2635230

Ghasemi Z, Varasteh AR, Moghadam M, Jalali SA, Anissian A, Sankian M. Sublingual immunotherapy with sal k1 expressing Lactococcus lactis down-regulates Th2 immune responses in BALB/c mice. Iran J Allergy Asthma Immunol. 2018 Jun;17(3):281-90.

Sarate PJ, Srutkova D, Geissler N, Schwarzer M, Schabussova I, Inic-Kanada A, et al. Pre- and neonatal imprinting on immunological homeostasis and epithelial barrier integrity by Escherichia coli Nissle 1917 prevents allergic poly-sensitization in mice. Front Immunol. 2021 Feb 17;11:612775. DOI: 10.3389/fimmu.2020.612775

Zhang K, Mirza WA, Ni P, Yu M, Wang C, Wang B, et al. Recombination Lactococcus lactis expressing Helicobacter pylori neutrophil-activating protein A attenuates food allergy symptoms in mice. FEMS Microbiol Lett. 2021 Apr 22;368(6):fnab034. DOI: 10.1093/femsle/fnab034

Ren C, Zhang Q, Wang G, Ai C, Hu M, Liu X, et al. Modulation of peanut-induced allergic immune responses by oral lactic acid bacteria-based vaccines in mice. Appl Microbiol Biotechnol. 2014;98(14):6353-64. DOI: 10.1007/s00253-014-5678-7

Shigemori S, Yonekura S, Sato T, Otani H, Shimosato T. Expression of the immunoreactive buckwheat major allergenic storage protein in Lactococcus lactis. Appl Microbiol Biotechnol. 2013 Apr;97(8):3603-11. DOI: 10.1007/s00253-012-4608-9

Cortes-Perez NG, Ah-Leung S, Bermúdez-Humarán LG, Corthier G, Langella P, Wal JM, et al. Allergy therapy by intranasal administration with recombinant Lactococcus lactis producing bovine β-lactoglobulin. Int Arch Allergy Immunol. 2009;150(1):25-31. DOI: 10.1159/000210377

Li J, Zhang W, Wang C, Yu Q, Dai R, Pei X. Lactococcus lactis expressing food-grade β-galactosidase alleviates lactose intolerance symptoms in post-weaning Balb/c mice. Appl Microbiol Biotechnol. 2012 Dec;96(6):1499-506. DOI: 10.1007/s00253-012-3977-4

de Azevedo MS, Innocentin S, Dorella FA, Rocha CS, Mariat D, Pontes DS, et al. Immunotherapy of allergic diseases using probiotics or recombinant probiotics. J Appl Microbiol. 2013 Aug;115(2):319-33. DOI: 10.1111/jam.12174

Zhou Z, Chen X, Sheng H, Shen X, Sun X, Yan Y, et al. Engineering probiotics as living diagnostics and therapeutics for improving human health. Microb Cell Fact. 2020 Mar 4;19(1):56. DOI: 10.1186/s12934-020-01318-z

Lubkowicz D, Ho CL, Hwang IY, Yew WS, Lee YS, Chang MW. Reprogramming Probiotic Lactobacillus reuteri as a biosensor for Staphylococcus aureus derived AIP-I detection. ACS Synth Biol. 2018 May 18;7(5):1229-37. DOI: 10.1021/acssynbio.8b00063

Borrero J, Chen Y, Dunny GM, Kaznessis YN. Modified lactic acid bacteria detect and inhibit multiresistant enterococci. ACS Synth Biol. 2015 Mar 20;4(3):299-306. DOI: 10.1021/sb500090b

Danino T, Prindle A, Kwong GA, Skalak M, Li H, Allen K, et al. Programmable probiotics for detection of cancer in urine. Sci Transl Med. 2015 May 27;7(289):289ra84. DOI: 10.1126/scitranslmed.aaa3519

Han X, Wang L, Li W, Li B, Yang Y, Yan H, et al. Use of green fluorescent protein to monitor Lactobacillus plantarum in the gastrointestinal tract of goats. Braz J Microbiol. 2015 Jul 1;46(3):849-54. DOI: 10.1590/S1517-838246320140556

Moon GS, Narbad A. Construction of a bioluminescent labelling plasmid vector for bifidobacteria. Korean J Food Sci Anim Resour. 2018 Sep;38(4):816-22. DOI: 10.5851/kosfa.2018.e17

Lee MS, Moon GS. In vivo imaging of Escherichia coli and Lactococcus lactis in murine intestines using a reporter luciferase gene. Food Sci Biotechnol. 2012 Jun;21(3):917-20. DOI: 10.1007/s10068-012-0120-3

Eom JE, Ahn WG, Her S, Moon GS. Construction of bioluminescent Lactobacillus casei CJNU 0588 for murine whole body imaging. Food Sci Biotechnol. 2015 Apr;24(2):595-9. DOI:10.1007/s10068-015-0077-0

Van Zyl WF, Deane SM, Dicks LM. In vivo bioluminescence imaging of the spatial and temporal colonization of lactobacillus plantarum 423 and enterococcus mundtii ST4SA in the intestinal tract of mice. BMC Microbiol. 2018 Oct 30;18(1):171. DOI: 10.1186/s12866-018-1315-4

Ferrer-Miralles N, Villaverde A. Bacterial cell factories for recombinant protein production; expanding the catalogue. Microb Cell Fact. 2013 Nov 18;12(1):113. DOI: 10.1186/1475-2859-12-113

Romero-Luna HE, Hernández-Mendoza A, González-Córdova AF, Peredo-Lovillo A. Bioactive peptides produced by engineered probiotics and other food-grade bacteria: a review. Food Chem X. 2021 Dec 22;13:100196. DOI: 10.1016/j.fochx.2021.100196

Li R, Wan X, Takala TM, Saris PE. Heterologous expression of the Leuconostoc bacteriocin leucocin C in probiotic yeast Saccharomyces boulardii. Probiotics Antimicrob Proteins. 2021 Feb;13(1):229-37. DOI: 10.1007/s12602-020-09676-1

Jiménez JJ, Diep DB, Borrero J, Gútiez L, Arbulu S, Nes IF, et al. Cloning strategies for heterologous expression of the bacteriocin enterocin A by Lactobacillus sakei Lb790, Lb. plantarum NC8 and Lb. casei CECT475. Microb Cell Fact. 2015 Oct 15;14(1):166. DOI: 10.1186/s12934-015-0346-x

Morales-Contreras JA, Rodríguez-Pérez JE, Álvarez-González CA, Martínez-López MC, Juárez-Rojop IE, Ávila-Fernández Á. Potential applications of recombinant bifidobacterial proteins in the food industry, biomedicine, process innovation and glycobiology. Food Sci Biotechnol. 2021 Aug 3;30(10):1277-91. DOI: 10.1007/s10068-021-00957-1

Sun Z, Yue Z, Yang X, Hao X, Song M, Li L, et al. Efficient phytase secretion and phytate degradation by recombinant Bifidobacterium longum JCM 1217. Front Microbiol. 2019 Apr 16;10:796. DOI: 10.3389/fmicb.2019.00796

Sauer M, Russmayer H, Grabherr R, Peterbauer CK, Marx H. The efficient clade: lactic acid bacteria for industrial chemical production. Trends Biotechnol. 2017 Aug;35(8):756-69. DOI: 10.1016/j.tibtech.2017.05.002

Yang B, Gao H, Stanton C, Ross RP, Zhang H, Chen YQ, et al. Bacterial conjugated linoleic acid production and their applications. Prog Lipid Res. 2017 Oct;68:26-36. DOI: 10.1016/j.plipres.2017.09.002

Amiri-Jami M, Abdelhamid AG, Hazaa M, Kakuda Y, Griffths MW. Recombinant production of omega-3 fatty acids by probiotic Escherichia coli Nissle 1917. FEMS Microbiol Lett. 2015 Oct;362(20):fnv166. DOI: 10.1093/femsle/fnv166

Altaib H, Kozakai T, Badr Y, Nakao H, El-Nouby MA, Yanase E, et al. Cell factory for γ-aminobutyric acid (GABA) production using Bifidobacterium adolescentis. Microb Cell Fact. 2022 Mar 7;21(1):33. DOI: 10.1186/s12934-021-01729-6

Lan YJ, Tan SI, Cheng SY, Ting WW, Xue C, Lin TH, et al. Development of Escherichia coli Nissle 1917 derivative by CRISPR/Cas9 and application for gamma-aminobutyric acid (GABA) production in antibiotic-free system. Biochem Eng J. 2021 Apr;168:107952. DOI:10.1016/j.bej.2021.107952

Lyu C, Yao L, Zhu Q, Mei J, Cao Y, Hu S, et al. Reconstruction of the glutamate decarboxylase system in Lactococcus lactis for biosynthesis of food-grade γ-aminobutyric acid. Appl Microbiol Biotechnol. 2021 May;105(10):4127-40. DOI: 10.1007/s00253-021-11328-5

Nguyen HM, Mathiesen G, Stelzer EM, Pham ML, Kuczkowska K, Mackenzie A, et al. Display of a β-mannanase and a chitosanase on the cell surface of Lactobacillus plantarum towards the development of whole-cell biocatalysts. Microb Cell Fact. 2016 Oct 4;15(1):169. DOI: 10.1186/s12934-016-0570-z

Su HH, Xu RY, Yang ZD, Guo YS, Gao JY, Mo LZ, et al. Green synthesis of isomaltulose from cane molasses by an immobilized recombinant Escherichia coli strain and its prebiotic activity. Lwt. 2021 May;143:111054. DOI: 10.1016/j.lwt.2021.111054

Jin Y, Yu S, Liu JJ, Yun EJ, Lee JW, Jin YS, et al. Production of neoagarooligosaccharides by probiotic yeast Saccharomyces cerevisiae var. boulardii engineered as a microbial cell factory. Microb Cell Fact. 2021 Aug 18;20(1):160. DOI: 10.1186/s12934-021-01644-w

Datta P, Fu L, Brodfuerer P, Dordick JS, Linhardt RJ. High density fermentation of probiotic E. coli Nissle 1917 towards heparosan production, characterization, and modification. Appl Microbiol Biotechnol. 2021 Feb;105(3):1051-62. DOI: 10.1007/s00253-020-11079-9

Jacouton E, Torres Maravilla E, Boucard AS, Pouderous N, Pessoa Vilela AP, et al. Anti-tumoral effects of recombinant Lactococcus lactis strain secreting IL-17A cytokine. Front Microbiol. 2019 Jan 23;9:3355. DOI: 10.3389/fmicb.2018.03355

Daliri EB, Lee BH, Oh DH. Safety of probiotics in health and disease. In: Singh RB, Watson RR, Takahashi T, editors. The role of functional food security in global health. Academic Press; 2019. p. 603-22. DOI: 10.1016/b978-0-12-813148-0.00034-7

Nadar Rajivgandhi G, Rtv V, Ramachandran G, Manoharan N. Industrial requirements and other techno-functional traits of probiotics. In: Dhanasekaran D, Sankaranarayanan A, editors. Advances in probiotics. Academic Press; 2021. p. 519-33. DOI: 10.1016/b978-0-12-822909-5.00030-7

van den Nieuwboer M, Claassen E. Dealing with the remaining controversies of probiotic safety. Benef Microbes. 2019 Jul 10;10(6):605-16. DOI: 10.3920/BM2018.0159




How to Cite

Khablenko A, Danylenko S, Yalovenko O, Duhan O, Potemskaia O, Prykhodko D. Recombinant Probiotic Preparations: Current State, Development and Application Prospects. Innov Biosyst Bioeng [Internet]. 2023Feb.15 [cited 2024May28];6(3-4):119-47. Available from: