Microbiology, Metabolites and Biotechnology

Microbiology, Metabolites and Biotechnology

The Emerging Role of Engineered Probiotics in Gastrointestinal Health: Mechanisms, Challenges, and Future Perspectives

Document Type : Review Paper

Authors
Kimiya Khani-Chegeni 1
Samaneh Sedighi-Khavidak 2
Mohammad Rabbani Khorasgani 3
Farnaz Mozayani 4
1 Department of Biology, Khor.C., Islamic Azad University, Khorramabad, Iran.
2 Department of Biology, Ashk.C., Islamic Azad University, Ashkezar, Iran. and Medical Biotechnology Research Center, Ashk.C., Islamic Azad University, Ashkezar, Iran.
3 Department of Biology, University of Isfahan, P.O. Box:81746-73441, Isfahan, Iran
4 School of Medicine, Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
10.22104/mmb.2026.7952.1188
Abstract
Traditional probiotics, such as Lactobacillus, Lactococcus, and Bifidobacteria, defined as live microorganisms used to manage gastrointestinal disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), have demonstrated variable clinical efficacy. The advent of synthetic biology has ushered in a paradigm shift, enabling the rational design and production of Next-Generation Probiotics (NGPs) or engineered strains with precise therapeutic and diagnostic functionalities at targeted gastrointestinal sites. This review discusses predominant molecular mechanisms employed by engineered probiotics, including enhanced biosynthesis of bioactive metabolites like short-chain fatty acids (SCFAs) and site-specific delivery of immunomodulatory cytokines such as interleukin-10 (IL-10). Additionally, critical biosafety considerations related to biocontainment and horizontal gene transfer )HGT) are evaluated, highlighting advanced genetic safeguards such as CRISPR-Cas–based kill switches to mitigate dissemination risks. Regulatory frameworks governing these live biotherapeutic products (LBPs) are also analyzed. Future directions encompass the integration of state-of-the-art gene editing technologies and GI biosensors for in vivo disease monitoring, as well as the potential for engineered probiotics in personalized medicine. Collectively, advancements in synthetic biology and genomics have propelled engineered probiotics as programmable live therapeutics, offering novel avenues for the prevention, diagnosis, and treatment of refractory gastrointestinal diseases. These approaches, while navigating biosafety and regulatory challenges, promise enhanced clinical efficacy and pave the way for precision microbiome interventions.
Keywords
Next-Generation Probiotics
Synthetic Biology
Bio-Containment
Horizontal Gene Transfer
Subjects
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Microbiology, Metabolites and Biotechnology
Volume 8, Issue 2
November 2025
Pages 121-130