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Investigating the Alleviating Effects of Bacillus cereus Administration on Colitis through Gut Microbiota Modulation
Published on: July 27, 2022
Triple-Functional Probiotics with Intracellularly Synthesized Selenium Nanoparticles for Colitis Therapy by
Puze Li1, Lichong Zhu1, Cheng Song1
1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Abstract:
The dysregulated macrophage phenotype, as the main cause of colitis, not only enhanced oxidative stress to exacerbate inflammatory responses but was closely related with gut microbial dysbiosis. It was needed to simultaneously address the three issues for the effective treatment of colitis, but it was not satisfied. Here, we developed "three-birds-one-stone" probiotics, named Se@EcN-C2/A2, for colitis treatment. Escherichia coli Nissle 1917 (EcN), a clinically approved probiotic, was used to intracellularly synthesize selenium (Se) nanoparticles by biomineralization, giving Se@EcN. Coating glycol chitosan and sodium alginate on the surface of Se@EcN (Se@EcN-C2/A2) endowed probiotics with high resistance to the harsh gastrointestinal tract environment and strong adhesion and targeting ability to the inflamed site of the colon to facilitate the uptake by M1 macrophages. Se@EcN-C2/A2 was metabolized to SeCys2 and MetSeCys to be involved in the synthesis of GPX2 and TXNRD1, which led to reaction oxygen species clearance to inhibit Toll-like receptor and nuclear factor κB signaling pathways to suppress inflammatory response and polarize M1 macrophages to M2 phenotypes by activating PI3K/AKT signaling pathways. In DSS-induced colitis mice, Se@EcN-C2/A2 exerted satisfactory therapeutic and prophylactic effects, including scavenging oxidative stress and regulating macrophage phenotypes to suppress inflammatory response and restore gut barrier functions. Moreover, the living probiotic EcN in the colon effectively regulated microbial dysbiosis by decreasing the abundance of Escherichia-Shigella and increasing the abundance of Lactobacillus and Bifidobacterium.
Insights
This study introduces Se@EcN-C2/A2, a novel probiotic that simultaneously targets oxidative stress, inflammation, and gut dysbiosis for effective colitis treatment. It demonstrates significant therapeutic and prophylactic effects in mice, restoring gut health.
Area of Science:
- Biomedical Engineering
- Microbiology
- Immunology
Background:
- Colitis pathogenesis involves dysregulated macrophage phenotypes, oxidative stress, and gut microbial dysbiosis.
- Current colitis treatments struggle to address these interconnected issues simultaneously.
- A multi-targeted therapeutic approach is crucial for effective colitis management.
Purpose of the Study:
- To develop a novel probiotic, Se@EcN-C2/A2, capable of simultaneously addressing oxidative stress, inflammation, and gut dysbiosis in colitis.
- To evaluate the therapeutic and prophylactic efficacy of Se@EcN-C2/A2 in a mouse model of colitis.
- To investigate the underlying mechanisms of Se@EcN-C2/A2 in regulating macrophage polarization and gut microbiota.
Main Methods:
- Engineered *Escherichia coli* Nissle 1917 (EcN) to synthesize selenium nanoparticles (Se@EcN).
- Coated Se@EcN with glycol chitosan and sodium alginate to create Se@EcN-C2/A2 for enhanced gastrointestinal stability and targeted delivery.
- Administered Se@EcN-C2/A2 to DSS-induced colitis mice and assessed therapeutic effects on oxidative stress, inflammation, macrophage polarization, gut barrier function, and microbial composition.
Main Results:
- Se@EcN-C2/A2 effectively scavenged reactive oxygen species and suppressed inflammatory signaling pathways (TLR and NF-κB).
- The probiotic polarized M1 macrophages to M2 phenotypes via PI3K/AKT activation, reducing inflammation.
- Se@EcN-C2/A2 demonstrated significant therapeutic and prophylactic effects in colitis mice, restoring gut barrier integrity and modulating gut microbiota by reducing *Escherichia-Shigella* and increasing *Lactobacillus* and *Bifidobacterium*.
Conclusions:
- Se@EcN-C2/A2 represents a promising "three-birds-one-stone" therapeutic strategy for colitis.
- The engineered probiotic effectively mitigates key pathological features of colitis, including oxidative stress, inflammation, and gut dysbiosis.
- This multi-targeted probiotic approach holds potential for future clinical applications in inflammatory bowel disease treatment.
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