Table 2.

Examples of genetically engineered probiotics.

Vehicle	Disease	Mechanism	References
Lactic acid bacteria	Arthritis	Production of anti-inflammatory cytokines like IL-4 and IL-10, which can help suppress TNF-α production and neutrophil influx in the joints and reduce inflammation.	[189]
B. ovatus D-6	Cancer	Increases the production of TNF-α-specific IgG and IgM in the body, promoting an immune response against cancer cells.	[190]
B. longum	Cancer	Expresses tumstatin or other anti-angiogenic proteins that have the potential for antitumor therapy in tumor-bearing mice by proliferation inhibition and apoptosis induction in vascular endothelial cells.	[189]
E. coli Nissle 1917	Cancer	Expresses glucose and ribose sugars receptor Trz1, which, upon activation, triggers the expression of a green fluorescent protein (GFP) reporter within tumors correlated with tumor cell viability. Targets and restricts mouse B16 melanoma and 4T1 breast tumors through the expression of azurin protein.	[191,192]
S. Typhimurium	Cancer	S. Typhimurium with a modified sidA gene undergoes lysis upon tetracycline exposure, leading to the release of agents causing cell cycle arrest in majority of MCF7 breast cancer cells in the subG1 population.	[193]
S. Typhimurium	Cancer	Employs quorum sensing-regulated lysis, causing the discharge of anti-cancer substances within tumors linked to heightened activation of T cells infiltrating tumors, swift regression of tumors, prevention of metastasis, and prolonged survival in preclinical models.	[194]
S. Typhimurium	Cancer	Expresses interferon-gamma (IFN-γ) fused to the N-terminal region of SipB, allowing for the efficient secretion of IFN-γ from the bacterium and enhancing the localized delivery of IFN-γ for improved melanoma cells cancer treatment outcomes.	[195]
B. acidifaciens JCM	Treatment of infection	Modulates host immune responses and enhances the production of gut IgA levels in gnotobiotic mice.	[196]
B. longum	Ulcerative colitis	Colonizes in the intestinal gut, expresses bioactive alpha-melanocyte-stimulating hormone (α-MSH) and exhibits a significant anti-inflammatory effect.	[197]
L. lactis	Crohn’s disease	Reducing inflammation and mucositis by secretion of cytokines.	[197]
B. subtilis	H. pylori	Displaying H. pylori antigens on its spore coat and eliciting a Th1/Th17-polarized immune response in a murine model showing potential as an oral vaccine candidate for H. pylori infection and reduction in stomach bacterial load.	[189,198]
L. lactis	Multidrug-resistant Enterococcus spp.	Detects Enterococcus faecalis pheromone cCF10 and responds by producing and secreting antienterococcal peptides (bacteriocins), which can kill multidrug-resistant E. faecalis.	[189]
Salmonella sp.	Salmonella and Cholera infection	S. Typhimurium vaccine strain expressing Vibrio cholera toxin antigen subunit-B heterologous antigen (CtxB) can protect against both salmonellosis and cholera infection. The polyvalent vaccine Z234-pMS101, which expresses CtxB antigen, increases mucosal response and pro-inflammatory cytokine production to be efficacious against both salmonellosis and cholera.	[199]
E. coli Nissle 1917	Hepatic steatosis	Expressing fructose dehydrogenase (FDH) or mannitol-2-dehydrogenase (mtIK), leading to reduction in lipid peroxidation, an increase in antioxidant enzyme activities, and the restoration of liver injury marker enzymes.	[200]
L. lactis	HIV infection	Oral immunization with L. lactis expressing Streptococcus pyogenes T3 pilus fused to an HIV antigen gag P24 (LL-Gag) induces strong mucosal immunity in the gut displaying 3-fold higher CD8 T cell responses.	[201]
L. plantarum NC8	Hypertension	Expressing angiotensin-converting enzyme inhibitory peptide (ACEIP) coding sequences from TFP and YFP joined by an arginine linker increasing the levels of nitric oxide in the plasma, heart, and kidney and reducing the levels of decrease in the levels of endothelin and angiotensin II.	[189]
L. lactis	IBD	Production and delivery interleukin-10 (IL-10) using stress-inducible controlled expression system and delivery of IL-10 cDNA cassette into host cells and LL-IL-27 mediated through mucosal delivery, resulting higher expression of anti-inflammatory cytokines.	[202,203,204]
B. longum	IBD	Produces and delivers IL-10 in vivo and regulates immune responses offering therapeutic benefits for inflammatory diseases such as inflammatory bowel disease (IBD) and ulcerative colitis.	[197]
Streptococcus gordonii	IBD	Recombinant strain of S. gordonii produces bioactive human interleukin 1 receptor antagonist (IL-1ra) through RVFP/IL-RA in vitro and could be suitable for selective targeting of the mucosal surface as a delivery system for inflammatory diseases such as IBD.	[205]
B. ovatus V975	Intestinal inflammation	Reduction in inflammatory infiltrate and mucin depletion in the colon, as well as a decrease in epithelial erosion symptoms of DSS-induced colitis in mice.	[190]
E. coli Nissle 1917	Obesity	EcN expressing acylphosphatidylethanolamines (NAPEs) or GLP-1 analog may have potential as a therapeutic intervention for obesity, leading to the inhibition of weight gain, food intake, adiposity, insulin resistance, and hepatosteatosis reduction and maintaining lower plasma leptin and insulin levels.	[206]
L. lactis SAGX0085	Oral and intestinal mucositis	Secretes human trefoil factor 1 (hTFF1), which is believed to promote cell differentiation and limit cell proliferation and apoptosis to potentially improve the repair of oral and intestinal epithelial damage.	[207]
L. gasseri	Type 1 diabetes	Expressing GLP-1(1-37) has been shown to reprogram intestinal epithelial cells into insulin-secreting cells in rats, leading to a reduction in blood glucose levels. In a study, diabetic rats fed with L. gasseri expressing GLP-1(1-37) had significantly higher insulin levels and were more glucose-tolerant than those fed with wild-type L. gasseri.	[208]
L. lactis	Type 1 diabetes	Secretes human pro-insulin and induces antigen-specific immune tolerance in T1D by delivering cytokines like IL-10 and IL-4 that can restore the tolerance of pancreatic beta cells.	[9]