Genetically Engineered Probiotics

As the dawn of genetic engineering has started breaking barriers across multiple sectors, there are microscopic but potent entities that could be at the epicenter of many innovations - microbes that live all around us and sometimes call us home. The human microbiome, comprising trillions of microorganisms, plays a vital role in maintaining overall health. Genetically engineered probiotics have the potential to positively influence the composition and function of the microbiome. With the successful advent of genetically engineered bacteria, the fields of probiotics and personal care products could be significantly impacted, leading to a series of groundbreaking innovations. 

Genetically engineered (GE) microorganisms have their genetic material altered through genetic engineering techniques. This equips them with new properties, enabling to produce useful substances, counteract certain processes or perform specific functions. This includes everything from producing insulin to treating water pollution and enhancing probiotics and personal care products.

There has been a growing number of reports focusing on the assessment of bioengineered bacterial strains as probiotics, paraprobiotics, and postbiotics.

Probiotics, often referred to as "good" bacteria, are live microorganisms that offer a health benefit when consumed, generally by improving or restoring the gut flora. The naturally occurring probiotic bacteria have been used in our diets for years, especially in fermented foods. Traditional probiotics are obtained from natural sources or cultured under controlled conditions, and their therapeutic potential is well-documented. However, probiotics could be given a new dimension through genetic modification: to enhance their functionalities and create customized solutions. 

By modifying the genes of bacteria, scientists can design strains with enhanced properties. For instance, Lactobacillus, a common strain found in our gut, can be engineered to produce therapeutic compounds such as short-chain fatty acids, antioxidants, and other metabolites that can be beneficial for gut health.

GE bacteria could be customized to target specific health issues. For example, some engineered probiotics are being developed to treat conditions like inflammatory bowel disease (IBD) and obesity. These probiotics can sense inflammation in the gut and release anti-inflammatory compounds, hence directly addressing the problem at its source. Genetically engineered bacteria to cure TMAU are also being investigated

The evaluation of bioengineered strains as probiotics is subjected to approval by regulatory authorities and is performed under strict biological conditions. However, the number of reports on the evaluation of bioengineered bacterial strains as probiotics (live cells), paraprobiotics (dead, non-viable cells) and postbiotics (physical-, chemical- or enzymatic-lysis of probiotic cells) is increasing. 

The personal care industry has seen a dramatic shift with the introduction of products that contain live bacteria, often referred to as "biotic" products. The focus has now shifted from eliminating all bacteria — the "anti-bacterial" approach — to promoting beneficial ones.

Genetically engineered bacteria are playing a significant role in this shift. For example, a bacterium named Nitrosomonas eutropha, which is commonly found in soil and water, is now engineered and added to skin care products. This bacterium metabolizes ammonia, a component of sweat, into nitrite and nitric oxide, ingredients that are beneficial for the skin. The result is a product that not only combats body odor but also enhances skin health.

Other skin care products employ engineered versions of Staphylococcus epidermidis, a skin microbiome resident, to produce antimicrobial peptides that prevent the colonization of harmful bacteria, helping maintain a balanced and healthy skin microbiome.

The application of genetically engineered bacteria in probiotics and personal care products is an area that continues to burgeon with immense possibilities. With the ever-growing understanding of microbiome's role in human health and disease, the era of personalized probiotics and care products designed for individual microbiome profiles may not be far.

It's worth noting, however, that this is a nascent field with potential ethical and safety concerns. Rigorous testing and regulations are necessary to ensure the safe use of these technologies. Further research will determine the ultimate success of these promising applications, unlocking a new world of microbiome-enhanced products for consumers around the globe.


Mugwanda K, Hamese S, Van Zyl WF, Prinsloo E, Du Plessis M, Dicks LMT, Thimiri Govinda Raj DB. Recent advances in genetic tools for engineering probiotic lactic acid bacteria. Biosci Rep. 2023 Jan 31;43(1):BSR20211299. doi: 10.1042/BSR20211299. PMID: 36597861; PMCID: PMC9842951.

Cuevas-González, P.F.; Liceaga, A.M.; Aguilar-Toalá, J.E. Postbiotics and paraprobiotics: From concepts to applications. Food Res. Int. 2020, 136, 109502.

Sadeghi, A.; Ebrahimi, M.; Kharazmi, M.S.; Jafari, S.M. Effects of microbial-derived biotics (meta/pharma/post-biotics) on the modulation of gut microbiome and metabolome. General aspects and emerging trends. Food Chem. 2023, 411, 135478. 


L. lactis AG019 developed by Precigen ActoBio for the treatment of Type 1 diabetes: Phase 1 and 2 completed: NCT03751007

L. gasseri: Duan F.F., Liu J.H. and March J.C. (2015) Engineered commensal bacteria reprogram intestinal cells into glucose-responsive insulin-secreting cells for the treatment of diabetes. Diabetes 64, 1794–1803 10.2337/db14-0635

Lc. lactis: Agarwal P., Khatri P., Billack B., Low W.K. and Shao J. (2014) Oral delivery of glucagon like peptide-1 by a recombinant Lactococcus lactis. Pharm. Res. 31, 3404–3414 10.1007/s11095-014-1430-3

E.-Coli-Nissle: Completed Trial: Investigation of the Effect of E.-Coli-Nissle as Supporting Therapy to Standard Care of Diabetes Mellitus Type II (PUNiDIA). ID NCT02144948; Sponsor GWT-TUD GmbH Investigation of the Effect of E.-Coli-Nissle as Supporting Therapy to Standard Care of Diabetes Mellitus Type II (PUNiDIA)Study Record | Beta


Lc. lactis NZ9000: Namai F., Shigemori S., Sudo K., Sato T., Yamamoto Y., Nigar al.. (2018) Recombinant mouse osteocalcin secreted by Lactococcus lactis promotes glucagon-like peptide-1 induction in STC-1 cells. Curr. Microbiol. 75, 92–98 10.1007/s00284-017-1354-3


Cancer therapy: Lc. lactis KiSS1 Human melanoma cell lines Expression plasmid pNZ401, nisin inducible promoter Cancer therapy for prevention of proliferation and migration of human colon carcinoma HT-29 cells: Holo H, Nes IF. High-frequency transformation, by electroporation, of Lactococcus lactis subsp. cremoris grown with glycine in osmotically stabilized media. Appl. Environ. Microbiol. 1989;55:3119–3123. [PMC free article]


Mutations incorporated in the chromosome of Lactobacillus reuteri and Lactococcus lactis without selection at frequencies ranging between 0.4% and 19%. This reduced the intrinsic vancomycin resistance of L. reuteri >100-fold: Van Pijkeren J.P.P. and Britton R.A. (2012) High efficiency recombineering in lactic acid bacteria. Nucleic Acids Res. 40, e76–e76 10.1093/nar/gks147


Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) delivering Spike protein Receptor-binding domain (RBD) for vaccine development: Li L., Wang M., Hao J., Han J., Fu T., Bai al.. (2021) Mucosal IgA response elicited by intranasal immunization of Lactobacillus plantarum expressing surface-displayed RBD protein of SARS-CoV-2. Int. J. Biol. Macromol. 190, 409–416 10.1016/j.ijbiomac.2021.08.232 [PMC free article] Phase 1 clinical trial: NCT04334980)

L. plantarum with SARS-CoV-2 spike protein(S) for vaccine development: Li L., Wang M., Hao J., Han J., Fu T., Bai al.. (2021) Mucosal IgA response elicited by intranasal immunization of Lactobacillus plantarum expressing surface-displayed RBD protein of SARS-CoV-2. Int. J. Biol. Macromol. 190, 409–416 10.1016/j.ijbiomac.2021.08.232 [PMC free article]

Lc. lactis with Human Papilloma Virus 16 E7 protein Ag (LL-E7) and biologically active murine IL-12: Ahrné S, Molin G, Axelsson L. Transformation of Lactobacillus reuteri with electroporation: studies on the erythromycin resistance plasmid pLUL631. Curr. Microbiol. 1992;24:199–205. (Cancer vaccine)

Lc. lactis with Glycosylated tyrosinase related protein-2 Josson K, Scheirlinck T, Michiels F, Platteeuw C, Stanssens P, Joos H, Dhaese P, Zabeau M, Mahillon J. Characterization of a gram-positive broad-host-range plasmid isolated from Lactobacillus hilgardii. Plasmid. 1989;21:9–20. (Cancer vaccine)

Bacillus Calmette-Guerin (BCG)  - modified Mycobacterium bovis (weakened TB bacteria) - Study Record | Beta - terminated


AG013 (genetically modified L. lactis bacteria engineered to secrete human Trefoil Factor 1: Study Record | Beta (completed)


L. reuteri: Durrer K.E., Allen M.S. and Hunt von Herbing I. (2017) Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU. Wilson BA (ed.). PloS ONE 12, e0176286 10.1371/journal.pone.0176286


Lc. lactis: Drouault S., Juste C., Marteau P., Renault P. and Corthier G. (2002) Oral Treatment with Lactococcus lactis Expressing Staphylococcus hyicus lipase enhances lipid digestion in pigs with induced pancreatic insufficiency. Appl. Environ. Microbiol. 68, 3166–3168 10.1128/AEM.68.6.3166-3168.2002 


Experiments are being planned to evaluate the in vitro effect of L. lactis subsp. cremoris WA2-67 (pJFQI) and L. lactis subsp. cremoris WA2-67 (pJFQIAI) on rainbow trout intestinal epithelial cells (RTgutGC) for a transcriptional analysis of several immune, intestinal, barrier-integrity and homeostasis genes and the induction of antimicrobial peptides (AMPs), as well as for their effect on the in vivo modulation of the intestinal microbiota and immune response of rainbow trout (Oncorhynchus mykiss, Walbaum) and turbot (Scophthalmus maximus): 

Feito J, Araújo C, Arbulu S, Contente D, Gómez-Sala B, Díaz-Formoso L, Muñoz-Atienza E, Borrero J, Cintas LM, Hernández PE. Design of Lactococcus lactis Strains Producing Garvicin A and/or Garvicin Q, Either Alone or Together with Nisin A or Nisin Z and High Antimicrobial Activity against Lactococcus garvieae. Foods. 2023 Mar 2;12(5):1063.


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