Inflammatory bowel disease (IBD) is a group of chronic and recurrent gastrointestinal disorders encompassing ulcerative colitis and Crohn’s disease, with a prevalence ranging from 6–8 million cases worldwide. Current clinical treatments (5-aminosalicylic acid, corticosteroids, and anti-TNF-alpha monoclonal antibodies) generally focus on alleviating symptoms, but these drugs have serious side effects; furthermore, they lead to limited drug accumulation in lesion areas, failing to achieve complete remission of the disease. One of the critical factors in IBD pathogenesis is dysbiosis in the microbiota, observed with a decrease in beneficial bacteria and an increase in pathogenic structures. Existing microbiota modulation applications such as probiotics, fecal microbiota transplantation (FMT), and exosomes bring significant problems upon oral administration, such as the risk of deactivation, immunological issues, storage difficulties, and inadequate colonization in the intestinal lumen. Therefore, the development of biomimetic nanocarrier structures that can overcome biological barriers by mimicking bacterial cell membrane components, gaining homologous targeting capability, and maintaining drug delivery capacity is emerging as a critical need in the treatment of IBD.
Liu and colleagues aimed to develop a therapeutic technique that specifically targets and manipulates Lactobacillus rhamnosus-GG (LGG), a commensal bacterial species, to restore intestinal structural homeostasis in the treatment of IBD. The researchers created miRNA-loaded biomimetic nanoparticles by combining LGG-derived bacterial extracellular vesicles (BEVs) with lipid nanoparticles (LNPs) to prevent the destruction of probiotics throughout the gastrointestinal tract. The core hypothesis of the study is that specifically delivering the mdo-miR-7267-3p miRNA to LGG via this system suppresses the ycnE gene in the bacteria, promoting bacterial proliferation and thus increasing the production of indole-3-carboxaldehyde (I3A), which repairs the intestinal barrier. This approach aims to address the targeting deficiencies in current treatments, alleviate colitis symptoms by regulating the homeostasis of the endogenous microbiota, and increase the effectiveness of standard drugs such as 5-ASA.
In this study, lipid nanoparticles (LNPs) with high encapsulation capacity, a size of 200 nm, and a positive charge were first produced using a microfluidic mixing method and optimized to ensure optimal bacterial uptake. Then, BEVs obtained from LGG cultures by ultracentrifugation were combined with the aforementioned LNPs using a mini extruder to create BEV-LNPs with homology targeting capability. The targeting specificity of the nanoparticles was comparatively tested in vitro on Escherichia coli (E. coli) and LGG using flow cytometry and confocal microscopy. Gastrointestinal stability was analyzed using gastric and intestinal fluids simulating fasting and fed states. In addition, therapeutic efficacy was evaluated through a dextran sulfate sodium-induced acute colitis model and a spontaneously developing chronic colitis model in IL-10 knockout (IL-10⁻/⁻) mice. Changes in the microbiota were assessed using 16S rRNA gene sequencing; inflammation markers (IL-6, TNF-α, IL-22), ELISA, and metabolite levels (especially I3A) were examined in detail using liquid chromatography–tandem mass spectrometry.
In conclusion, it was observed that the BEV-LNP construct demonstrated superior stability compared to traditional LNPs, particularly under fasting conditions and challenging gastrointestinal environmental conditions (acids and enzymes), and effectively delivered miRNA to the distal gastrointestinal tract, particularly the colon. Through a homologous targeting mechanism, the system specifically targeted the miRNA to LGG bacteria, suppressing bacterial ycnE gene expression and significantly increasing I3A production. Increased I3A levels were proven to activate the AhR (aryl hydrocarbon receptor)-IL-22 signaling pathway, repairing the intestinal epithelial barrier via ZO-1 and Occludin proteins and reducing inflammation. Combined with 5-ASA, the standard treatment in acute and chronic colitis models, this method prevented colon shortening, minimized tissue damage, and restored microbiota balance by increasing the number of Lactobacillus species bacteria. This method is expected to serve as a guide for future multidimensional and diverse therapeutic approaches for IBD.
Author: Melih Soner Başbey
Editor: Sudenur Dinç
Reference: Liu, W., Yang, J., Wei, Z., Kong, W., Dong, Z., Wei, Y., Zhuang, J., & Qi, J. (2025). miRNA-loaded biomimetic nanoparticles orchestrate gut microbe to ameliorate inflammatory bowel disease. Science advances, 11(47), eadw5984. https://doi.org/10.1126/sciadv.adw5984
-Bioinfocodes Scientific News Service-
News articles prepared by our team members, reviewing and compiling scientific research
published in journals with and impact factor greater than 20 (click here for the list)