Lactic Acid Bacteria as Mucosal Delivery Systems for Therapeutic Applications

Lactic acid bacteria (LAB) represent a versatile class of non-sporing, Gram-positive microorganisms with a long history of safe use in food fermentations and as probiotics. Their intrinsic ability to survive passage through the gastrointestinal tract, combined with well-developed genetic tools, has positioned LAB as promising live delivery vectors for mucosal administration of therapeutic agents. By engineering strains such as Lactococcus lactis and various Lactobacillus species, researchers have established platforms for the controlled synthesis and presentation of antigens, cytokines and enzymes at mucosal surfaces. Strategies include secretion of soluble factors, surface display via anchoring domains or non-covalent binding modules, and delivery of DNA vaccines. These approaches exploit the immunological landscape of mucosal tissues to elicit local and systemic responses, offering needle-free vaccination, anti-inflammatory treatment for inflammatory bowel disease, and interventions in metabolic disorders. Advances in safety profiling, inducible expression systems and strain optimisation have improved both the efficacy and containment of recombinant LAB. Beyond therapeutic proteins, LAB can be formulated as dry powders, gels or edible matrices, enabling diverse routes of administration such as oral, intranasal or vaginal delivery. Collectively, the field has matured to the point where clinical translation is within reach, with early-phase human trials underway for selected applications. The global burden of mucosa-borne infections and chronic inflammatory conditions underscores the potential impact of LAB-based delivery systems on public health and personalised medicine.

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Lactic Acid Bacteria as Mucosal Delivery Systems for Therapeutic Applications publication trend

The graph below shows the total number of articles in lactic acid bacteria as mucosal delivery systems for therapeutic applications across all publications each year (not limited to Nature Index journals).

Technical terms

Mucosal delivery: Administration of therapeutic agents directly to the mucous membranes lining the gut, respiratory or urogenital tracts to induce local and systemic immune responses.

Live bacterial vector: A genetically modified microorganism used as a carrier to synthesise and present bioactive molecules at mucosal surfaces.

Bacterial-like particles (BLPs): Non-living cell wall derivatives of LAB engineered to display antigens or adjuvants for mucosal immunisation.

Surface display: The anchoring of heterologous proteins to the bacterial cell envelope via signal peptides and anchor domains to expose functional epitopes to the host immune system.

References

1. Genetically engineered bacterial‐like particles induced specific cellular and humoral immunity as effective tick‐borne encephalitis virus vaccine. Aggregate (2023).
2. A review on Lactococcus lactis: from food to factory. Microbial Cell Factories (2017).
3. Display of recombinant proteins at the surface of lactic acid bacteria: strategies and applications. Microbial Cell Factories (2016).
4. Bacterium-Like Particles for Efficient Immune Stimulation of Existing Vaccines and New Subunit Vaccines in Mucosal Applications. Frontiers in Immunology (2013).
5. Lactococci and lactobacilli as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Microbial Cell Factories (2011).
6. Immunomodulatory mechanisms of lactobacilli. Microbial Cell Factories (2011).
7. Protein secretion in Lactococcus lactis: an efficient way to increase the overall heterologous protein production. Microbial Cell Factories (2005).
8. Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis. Gut Pathogens (2014).
9. Lactic acid bacteria: reviewing the potential of a promising delivery live vector for biomedical purposes. Microbial Cell Factories (2015).
10. Lactic acid bacteria—20 years exploring their potential as live vectors for mucosal vaccination. Applied Microbiology and Biotechnology (2015).
11. Safety Aspects of Genetically Modified Lactic Acid Bacteria. Microorganisms (2020).