Table 1.
Selected preclinical evidence showing beneficial effects of gm-immunobiotics in treatment of gastrointestinal tract inflammation.
| Strains | Recombinant protein | Disease model | Outcome | Efficacy | Potential mechanisms | Reference |
|---|---|---|---|---|---|---|
| Lc. lactis MG1363/NZ9000 | IL-10 | mDAC, mTAC, mIL-10−/− | Reduction in MS, HS, and IM (MPO, Cox-2, SAA) | CC = WT/VC < Objects | Immunomodulation | (33–37) |
| Modulation of P/AICy | ||||||
| Lc. lactis MG1363 | IL-27 | mTTC, mDAC | Reduction in Mo, MS, and HS | CC = Systemic IL-27 = VC < Object | Immunomodulation | (38) |
| Modulation of P/AICy and PTc | MG1363-IL-10 < Object | |||||
| Lc. lactis NZ9000 | Elafin/SLPI | mDAC, mDCC, mTTC, hIEC | Reduction in MS, HS, CT, IIP, and IM (PL, MPO, PICy, PIL) | CC ≤ WT < NZ9000-IL-10/TGF-β < Objects | Reduction in elastolytic activity | (33, 39) |
| Lc. lactis NZ9000 | HO-1 | mDAC | Reduction in MS, HS, and CS | CC = VC < Object | Immunomodulation | (40) |
| Modulation of P/AICy | ||||||
| Lb. casei BL23 | Cat/SOD | mDAC, mTAC | Reduction in MS, HS, and LMT | CC ≤ WT/VC < Objects | Reduction in oxidative stress | (15, 17, 18) |
| Modulation of P/AICy | Immunomodulation | |||||
| Lb. casei BLS | α-MSH | mDAC | Reduction in Mo, MS, HS, CS, and IM (MPO, NF-κB) | CC ≤ WT < Object | Immunomodulation | (23) |
| Modulation of P/AICy | ||||||
| S. thermophilus CRL807 | Cat/SOD | mTAC | Reduction in Mo, MS, HS, and LMT | CC < WT < Objects | Reduction in oxidative stress | (13) |
| Modulation of CPIc | Immunomodulation | |||||
| B. longum NCC2705 | IL-10 | mDAC | Reduction in Mo, MS, HS, CS, and IM (MPO, NF-κB) | CC < WT/VC < Object | Immunomodulation | (21, 22) |
| Modulation of PTc and P/AICy | ||||||
| EcN | AvCys | mDAC, pPWD, hIEC | Reduction in MS, HS, CS, IIP, and IM (PIM, PICh, PICy) | CC ≤ WT < Object | Immunomodulation | (24) |
| Increase in Treg, TER | Improvement of intestinal barrier function | |||||
Lc., Lactococcus; Lb., Lactobacillus; S. thermophilus, Streptococcus salivarius subsp. thermophilus; B., Bifidobacterium; EcN, Escherichia coli Nissle 1917; IL-10, interleukin 10; IL-27, interleukin 27; SLPI, secretory leukocyte protease inhibitor; HO-1, heme oxygenase-1; SOD, superoxide dismutase; Cat, catalase; α-MSH, α-melanocyte-stimulating hormone; AvCys, cystatin from Acanthocheilonema viteae; mDAC, murine dextran sulfate sodium-induced acute colitis; mTAC, murine 2,4,6-trinitrobenzene sulfonic acid-induced acute colitis; mIL-10−/−, spontaneous colitis in IL-10-deficient mice; mTTC, murine T-cell transfer-induced enterocolitis; mDCC, murine dextran sulfate sodium-induced chronic colitis; hIEC, human intestinal epithelial cells; pPWD, porcine post-weaning diarrhea; MS, macroscopic symptoms; HS, histological symptoms; IM, mediators of inflammation; MPO, myeloperoxidase activity; Cox-2, cyclooxygenase-2 activity; SAA, serum amyloid A; P/AICy, pro-/anti-inflammatory cytokines; Mo, mortality; PTc, phenotypes of T-cell; CT, colon thickening; IIP, intestinal epithelial permeability; PL, proteolytic activity; PICy, pro-inflammatory cytokines; PIL, pro-inflammatory leukocytes; CS, colon shortening; LMT, liver microbial translocation; NF-κB, nuclear factor-κB; CPIc, cytokine phenotypes of immune cells; PIM, pro-inflammatory macrophages; PICh, pro-inflammatory chemokines; Treg, regulatory T-cell; TER, transendothelial electrical resistance; CC, colitis control; WT, wild-type strain; VC, vector control; MG1363-IL-10, IL-10-secreting Lactococcus lactis MG1363; NZ9000-IL-10/TGF-β, IL-10- or TGF-β-secreting Lactococcus lactis NZ9000.