Engineered probiotics emerge as programmable living medicines for complex diseases

This review synthesizes rapid advances showing that programmable bacteria can target tumors, calm chronic inflammation, correct metabolic imbalances, and combat drug-resistant infections by acting as precise delivery vehicles, metabolic assistants, and immune modulators. Beyond summarizing breakthroughs, the work clarifies why engineered probiotics could enable safer, localized, and more durable treatments than conventional drugs, pointing toward future clinical applications that integrate synthetic biology with microbiome science to address complex, multifactorial diseases.

Dysbiosis—imbalances in microbial composition or function—has been linked to cancers, inflammatory bowel disease, metabolic disorders such as diabetes and obesity, and recurrent infections. Traditional probiotics can help restore balance, but their effects are often modest and nonspecific. Advances in synthetic biology have changed this landscape by enabling microbes to be engineered with genetic circuits, biosensors, and controllable payloads. These tools allow probiotics to detect disease-specific signals, produce therapeutic molecules in situ, and respond dynamically to their environment. At the same time, safer genetic designs—such as non-antibiotic selection markers and environmentally contained circuits—are being developed to address biosafety concerns. Together, these trends have elevated engineered probiotics from dietary supplements to programmable therapeutic platforms poised to complement or, in some cases, replace existing treatments.

A study (DOI: 10.1016/j.bidere.2025.100039) published in BioDesign Research on 15 July 2025 by Jifeng Yuan’s team, Xiamen University, reveals that engineered probiotics can be rationally designed to diagnose, target, and treat diverse diseases through four core functions: precision delivery of therapeutics, metabolic assistance, restoration of microenvironmental homeostasis, and targeted immune activation.

In outlining the field, this review organizes recent advances by disease area and mechanism. In cancer therapy, engineered bacteria exploit their ability to preferentially colonize hypoxic tumors, where they release cytokines, prodrug-converting enzymes, nanobodies, or immune checkpoint inhibitors directly at the disease site, minimizing systemic toxicity. Some designs remodel the tumor microenvironment by recruiting immune cells or altering local metabolism, while others integrate light, heat, or ultrasound-responsive switches for spatiotemporal control. For inflammatory bowel disease, engineered probiotics secrete anti-inflammatory cytokines, short-chain fatty acids, antioxidant enzymes, or neutralizing nanobodies to strengthen the intestinal barrier and rebalance immune signaling, with several systems also acting as noninvasive sensors of disease activity. In metabolic disorders, living therapeutics are programmed to produce hormones such as GLP-1, degrade toxic metabolites like ammonia or phenylalanine, or modulate energy balance, offering alternatives to lifelong dietary restriction or injectable drugs. Against infectious diseases, engineered probiotics detect pathogens, disrupt biofilms, neutralize toxins, or restore microbiome-mediated colonization resistance, providing strategies that bypass traditional antibiotics. Across these applications, advances in CRISPR-based genome editing and modular genetic toolkits are accelerating design cycles and expanding the repertoire of treatable conditions.

In summary, this review portrays engineered probiotics as versatile, next-generation therapeutics that merge the adaptability of living systems with the precision of modern engineering. By functioning simultaneously as sensors, factories, and delivery vehicles, these microbes offer new ways to treat diseases that have proven resistant to conventional approaches. While significant work remains to ensure safety, consistency, and regulatory readiness, the trajectory outlined here suggests that programmable probiotics could become integral components of future medicine, enabling personalized, localized, and sustainable interventions across oncology, immunology, metabolism, and infectious disease.

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References

DOI

10.1016/j.bidere.2025.100039

Original Source URL

https://doi.org/10.1016/j.bidere.2025.100039

Funding information

This work was supported by the National Key R&D Program of China (grant no. 2024YFC3407000), the National Natural Science Foundation of China (grant no. 32270087), the Fundamental Research Funds for the Central Universities (grant no. 20720240120), and ZhenSheng Biotech.

About BioDesign Research

BioDesign Research is dedicated to information exchange in the interdisciplinary field of biosystems design. Its unique mission is to pave the way towards the predictable de novo design and assessment of engineered or reengineered living organisms using rational or automated methods to address global challenges in health, agriculture, and the environment.