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Review
. 2022 May 13;23(10):5466.
doi: 10.3390/ijms23105466.

Next-Generation Probiotics for Inflammatory Bowel Disease

Marcella Pesce  1 , Luisa Seguella  2 , Alessandro Del Re  2 , Jie Lu  3 , Irene Palenca  2 , Chiara Corpetti  2 , Sara Rurgo  1 , Walter Sanseverino  4 , Giovanni Sarnelli  1   4 , Giuseppe Esposito  2   4
Affiliations
Review

Next-Generation Probiotics for Inflammatory Bowel Disease

Marcella Pesce et al. Int J Mol Sci. .

Abstract

Engineered probiotics represent a cutting-edge therapy in intestinal inflammatory disease (IBD). Genetically modified bacteria have provided a new strategy to release therapeutically operative molecules in the intestine and have grown into promising new therapies for IBD. Current IBD treatments, such as corticosteroids and immunosuppressants, are associated with relevant side effects and a significant proportion of patients are dependent on these therapies, thus exposing them to the risk of relevant long-term side effects. Discovering new and effective therapeutic strategies is a worldwide goal in this research field and engineered probiotics could potentially provide a viable solution. This review aims at describing the proceeding of bacterial engineering and how genetically modified probiotics may represent a promising new biotechnological approach in IBD treatment.

Keywords: bioengineering; biosensors; biotherapeutics; inflammatory bowel disease; probiotics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Live biotherapeutics as new treatments for inflammatory intestinal diseases. Advances in the use of probiotics led to the development of engineered bacteria that act as intestinal biosensors, which detect specific biomarkers and work as diagnostic tools, and/or drug delivery systems able to release therapeutic substances directly into the intestinal lumen. Plasmids are the major vector for inducing recombinant DNA expression into desired probiotic strains. Despite diverse plasmids encoding for immunoregulatory cytokines, reporter substrate, or anti-inflammatory mediators being engaged in probiotics bioengineering, distinct regions are generally recognized: DNA replication origin, an antibiotic resistance gene, and the “Multiple Cloning Site” where exogenous DNA fragments are inserted by restriction enzymes.
Figure 2
Figure 2
Main approaches in probiotics engineering exploited in IBD. Biosensors can induce the expression of a reporter (usually a fluorescent marker) upon detecting specific biomarkers of inflammation. Biotherapeutics are able to produce at the mucosal surface a therapeutic molecule either constitutively or following the activation of an exogenous substrate (inducible systems). Sense and respond systems incorporate the technology of biosensors by responding to specific biomarkers of inflammation with the production of a therapeutic molecule.
Figure 3
Figure 3
Current advances and concerns in developing live biotherapeutics.
See this image and copyright information in PMC

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