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Figure 2. Mechanism of intestinal delivery of IL-27 by engineered LL-IL-27 for the treatment of IBD (Created with https://BioRender.
com). IBD: Inflammatory bowel disease.

short in vivo half-life limits clinical efficacy . In vivo drug delivery systems based on engineered bacteria
[49]
offer a promising solution to this challenge. As mentioned earlier, probiotics have demonstrated significant
potential in the treatment of T2D, making them ideal candidates as chassis bacteria for the development of
engineered strains. Engineered strains such as Lactococcus lactis (LL-pUBGLP-1) and Lactobacillus
[50]
plantarum (L. plantarum-pMG36e-GLP-1) [7,51] , transformed with plasmids containing GLP-1 cDNA, can
effectively produce and deliver GLP-1 orally, significantly enhancing its therapeutic potential. In animal
models and clinical trials, oral administration of Lactobacillus plantarum-pMG36e-GLP-1 reduced
pathogenic bacteria such as Prevotella and increased beneficial butyrate-producing Alistipes spp. in the gut
of spontaneous T2D monkeys, improving intestinal dysbiosis [Figure 1B]. Additionally, Lactobacillus
[51]
plantarum-pMG36e-GLP-1 has shown efficacy in mitigating high-fat diet-induced obesity in mice by
promoting fatty acid oxidation and modulating intestinal flora . In addition, engineered Lactococcus lactis
[52]
strains for the treatment of type 1 diabetes (T1D) are under development. For example, an engineered strain
of Lactococcus lactis that secretes the intact insulin autoantigen and the immunomodulatory cytokine IL-10
has been shown to successfully cure diabetes in non-obese diabetic (NOD) mice when used in conjunction
with low-dose systemic anti-CD3 antibody therapy .
[53]

E. coli Nissle 1917, a probiotic, exerts influence on glycemic responses through intricate host interactions
beyond mere glucose uptake . Like probiotic Lactobacilli, E. coli Nissle 1917 can be genetically engineered
[54]