Metabolite produced by gut microbiota from pomegranates reduces inflammatory bowel disease.

It is known that inflammatory bowel diseases (IBD) consisting of Crohn’s and ulcerative colitis are caused by dysregulation of the immune system leading to intestinal inflammation and microbial changes. Numerous studies highlight alterations in gut microbiota and their metabolites with adverse outcomes in cancer, IBD, neurological disorders, obesity, and diabetes.  Now, a study from researchers at University of Louisville shows that a microbial metabolite, Urolithin A, derived from a compound found in berries and pomegranates, can reduce and protect against IBD.  The team have determined that Urolithin A and its synthetic counterpart, UAS03, ease IBD by increasing proteins which tighten epithelial cell junctions in the gut and reducing gut inflammation in animal models.  The opensource study is published in the journal Nature Communications.

Previous studies show that microbiota and their metabolites are in close proximity to the gut epithelium which constitutes a single cell-layer maintained by tight junction proteins, which separate host components from the external environment.  Levels of tight junction proteins are significantly reduced under IBD leading to increased gut permeability to noxious substances resulting in inflammatory responses. However, the functional dynamics of microbiota and their metabolites in IBDs are unknown.  The current study shows how Urolithin A and its synthetic counterpart, UAS03, reduce inflammation, restore gut barrier integrity, and protect against colitis.

The current study shows that Urolithin A, a microbial metabolite derived from polyphenolics of berries and pomegranate fruits, and its synthetic analogue, UAS03, significantly enhance gut barrier function and inhibit unwarranted inflammation in mice.  Results show that Urolithin A and UAS03 exert their barrier functions through activation of aryl hydrocarbon receptor-nuclear factor erythroid 2–related factor 2-dependent pathways to upregulate epithelial tight junction proteins. Data findings show treatment with these compounds lessen colitis symptoms in pre-clinical models by remedying barrier dysfunction and reducing inflammation.

The lab state their results highlight how microbial metabolites provide two-pronged beneficial activities at gut epithelium by enhancing barrier functions and reducing inflammation to protect from colonic diseases.   They go on to add that oral treatment with Urolithin A/UAS03 significantly alleviate systemic inflammation and colitis in an animal model suggesting potential therapeutic applications for the treatment of IBD.

The team surmise their data shows that Urolithin A, a microbial metabolite derived from pomegranate fruits, and its analogue, UAS03 ease IBDs by enhancing gut barrier function and reducing inflammation.  For the future, the researchers state that Urolithin A/UAS03 could not only be efficacious in IBD-related diseases, it may also have implications in other disorders involving barrier dysfunction and inflammation such as alcohol liver diseases, neurological disorders, and colon cancers.

Source: University of Louisville




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