Highly painful in nature, 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 the University of Louisville shows a microbial metabolite, Urolithin A, derived from a compound found in berries and pomegranates, can reduce and protect against IBD.  The team has determined Urolithin A and its synthetic counterpart, UAS03, can ease IBD by increasing proteins capable of tightening epithelial cell junctions in the gut as well as reducing gut inflammation in animal models.  The opensource study is published in the journal Nature Communications.

Previous studies show the microbiota and their metabolites are in close proximity to the gut epithelium, a barrier consisting of a single cell-layer maintained by tight junction proteins responsible for separating 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 IBD 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 Urolithin A, a microbial metabolite derived from polyphenolics of berries and pomegranate fruits, and its synthetic analog, UAS03, significantly enhance gut barrier function and inhibit unwarranted inflammation in mice.  Results show 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 preclinical models by remedying barrier dysfunction and reducing inflammation.

The lab states 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 oral treatment with Urolithin A/UAS03 significantly alleviates systemic inflammation and colitis in an animal model suggesting potential therapeutic applications for the treatment of IBD.

The team surmises their data shows Urolithin A, a microbial metabolite derived from pomegranate fruits, and its analog, UAS03, ease IBDs by enhancing gut barrier function and reducing inflammation.  For the future, the researchers state Urolithin A/UAS03 could be efficacious in IBD-related diseases, and may also have implications in other disorders involving barrier dysfunction and inflammation.

Source: University of Louisville

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