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Page 2 of 25 Luo et al. Microbiome Res Rep 2025;4:10 https://dx.doi.org/10.20517/mrr.2024.57

INTRODUCTION
Probiotics are defined as “live microorganisms that, when administered in sufficient quantities, provide
[1]
health benefits to the host” . Research has increasingly focused on exploring the genetic structure and
biological properties of diverse probiotics. Especially as the well-deserved hotspot, in-depth exploration of
Lactobacillus and Bifidobacterium facilitates the identification and manipulation of crucial metabolic
[2]
pathways and regulatory mechanisms . Progressively clearer genetic backgrounds and inherent safety help
make probiotics excellent vectors for engineered modifications.

Technological innovations in synthetic biology, high-throughput sequencing, omics, synthetic genomics,
and other advanced fields have provided novel perspectives for the study of probiotics. Technologies like
genetic programming and high-throughput sequencing enable the precise engineering of biological systems,
analogous to techniques in electrical engineering . Engineered bacteria are genetically modified to express
[3]
[4]
exogenous genes or execute specific biological functions for treating, preventing, or diagnosing diseases .
Animal studies have demonstrated that engineered bacteria can influence a wide range of conditions
[8]
[7]
[6]
including tumors , inflammatory bowel disease (IBD) , diabetes , and neurodegenerative disorders ,
[5]
spanning various categories such as infections, metabolism, and oncology. Some have progressed to clinical
trials, such as Escherichia coli Nissle 1917 (EcN) engineered for colorectal cancer detection and treatment .
[9]
Engineered bacteria exhibit promising potential in vivo, leveraging both their inherent probiotic traits and
engineered functionalities to enhance therapeutic efficacy.
This paper reviews current research on the applications and mechanisms of engineered bacteria for treating
IBD, metabolic disorders, neurodegenerative conditions, and cancer. We also review the utilization of
biosensors and mucosal vaccines built on engineered bacteria. Finally, we summarize the advantages and
drawbacks of engineered bacteria in disease management.

THE PREDECESSOR OF ENGINEERED BACTERIA - PROBIOTICS
Although many food supplements contain active microorganisms, they are categorized as probiotics only if
[10]
they have been conclusively shown to benefit human health . Common sources of widely used probiotics
such as Lactobacillus and Bifidobacterium spp. include fermented foods, the human gut and vagina, and
[2]
various plants . Numerous animal studies have demonstrated that probiotics can enhance intestinal
microecology, modulate host immunity and metabolism, provide resistance against infections, and
potentially combat tumors. These effects depend on the probiotic itself or its secretions. For example, in the
intestine, probiotics preempt the adhesion sites on intestinal epithelial cells through their adhesion proteins,
thereby reducing the colonization of pathogenic bacteria . Probiotics also secrete bacteriocins that inhibit
[11]
the growth and proliferation of pathogenic bacteria such as Listeria, Clostridium, and Salmonella through
mechanisms including pore formation, which disrupts the selective permeability of the target cell
[13]
membrane , interference with cell wall synthesis , and enhancement of the host’s immune response .
[12]
[14]
Notably, significant progress has been made in cancer therapy, such as the discovery that Lactobacillus
reuteri ATCC BAA-2837 and its metabolite indole-3-aldehyde can enhance the effectiveness of immune
checkpoint inhibitors in treating melanoma . Recent clinical trials have also highlighted probiotics’
[15]
potential in managing conditions like anxiety and depression , irritable bowel syndrome , functional
[16]
[17]
[18]
[19]
dyspepsia , and postoperative constipation . These findings underscore the promising role of probiotics
in disease management. Strategies for microecological regulation of the human gut commonly include
probiotic supplementation and fecal microbiota transplantation (FMT). However, these nonspecific
approaches can have serious consequences due to the limited understanding of host-microbiota
interactions. For instance, a patient with acute promyelocytic leukemia who consumed probiotic-enriched