New Drug Candidate for Ulcerative Colitis

Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease (IBD) that affects more than 5 million patients worldwide. Studies have indicated that UC development is a long-term process that includes various unclear etiologies.

There is accumulating evidence that shows that dysbiosis (irregular gut microbiota composition) is associated with the progression of UC. Recently developed fecal microbiota transplantation (FMT) technologies have offered promising new approaches for modulating dysbiosis to treat UC. However, FMT requires prolonged treatment and may cause many side effects. 

In a recently published study, researchers in the Institute for Biomedical Sciences at Georgia State University have developed a new oral treatment that focuses on reducing inflammation in gut microbiota. Their research appears published in the journal Pharmaceutics. 

Reshaping Gut Microbial Metabolites to Decrease Inflammation

For the study, the team used a mouse model of chronic inflammation using interleukin-10 knockout, which replicates the features of UC in humans. 

The team collected feces from 6-week-old non-inflamed and 10-week-old inflamed IL-10 KO mice and cultured the 10-week-old fecal microbiota with phosphate-buffered saline (PBS), free M13, or empty nLNP-containing medium.

The researchers found that M13-loaded natural-lipid nanoparticle (M13/nLNP) modified the composition of the ex vivo-cultured inflamed gut microbiota and its secreted metabolites. They found that M13/nLNP shifted the inflamed microbiota composition toward the non-inflamed direction. 

When these metabolites were orally administered to mice, they showed strong protection against the formation of chronic inflammation. 

The study demonstrated that modifying microbiota outside of the host using M13/nLNP effectively changed the microbial-secreted metabolites and that orally transferring these metabolites, as they did in the study might be an effective therapeutic approach for UC treatment. 

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Source:

Chunhya Yang, et al. settings Prevention of Ulcerative Colitis by Autologous Metabolite Transfer from Colitogenic Microbiota Treated with Lipid Nanoparticles Encapsulating an Anti-Inflammatory Drug Candidate. 2022. Pharmaceutics.  https://doi.org/10.3390/pharmaceutics14061233 

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