Microbial Metabolite from Berry- and Pomegranate-Rich Diet Protects against Inflammatory Bowel Diseases

Urolithin A, a major microbial metabolite derived from polyphenolic compounds of berries and pomegranate fruits, and its synthetic structural analog, can reduce and protect against inflammatory bowel diseases (ulcerative colitis or Crohn’s disease), according to new research from the University of Louisville and the Institute for Stem Cell Biology and Regenerative Medicine (inStem).

Singh et al show that urolithin A and its potent synthetic analog, UAS03, significantly enhance gut barrier function and inhibit unwarranted inflammation. Image credit: Praveen Kumar Vemula, Institute for Stem Cell Biology and Regenerative Medicine / Venkatakrishna Jala, University of Louisville.

University of Louisville’s Dr. Venkatakrishna Jala and colleagues found that urolithin A and its synthetic counterpart, UAS03, mitigate inflammatory bowel diseases by increasing proteins that tighten epithelial cell junctions in the gut and reducing gut inflammation in animal models.

Tight junctions in the gut barrier prevent inappropriate microorganisms and toxins from leaking out, causing inflammation characteristic of inflammatory bowel diseases.

“The INIA P815 strain of the gut bacterium Bifidobacterium pseudocatenulatum has the ability to generate urolithin A from ellagic acid, a compound found in berries and pomegranates,” Dr. Jala and co-authors said.

“Variations in urolithin A levels, despite consumption of foods containing ellagic acid, may be the result of varied populations of bacteria responsible for the production of urolithin A from one individual to another, and some individuals may not have the bacteria at all.”

While encouraging natural levels of urolithin A in the gut by consuming the appropriate foods and protecting populations of beneficial bacteria should have positive health effects, the study authors believe the use of the more stable synthetic UAS03 may prove to be therapeutically effective in cases of acute colitis.

“Microbes in our gut have evolved to generate beneficial microbial metabolites in the vicinity of the gut barrier,” Dr. Jala said.

“However, this requires us to protect and harbor the appropriate gut microbiota and consume a healthy diet.”

“Our study shows that direct consumption of urolithin A or its analog can compensate for a lack of the specific bacteria responsible for production of urolithin A and continuous consumption of pomegranates and berries.”

“The general belief thus far in the field is that urolithins exert beneficial effects through their anti-inflammatory, anti-oxidative properties,” said study first author Dr. Rajbir Singh, a postdoctoral researcher at the University of Louisville.

“We have for the first time discovered that their mode of function also includes repairing the gut barrier dysfunction and maintaining barrier integrity.”

“Another key finding is that urolithin A and UAS03 show both therapeutic and protective effects,” said study co-author Professor Haribabu Bodduluri, also from the University of Louisville.

“Administration of urolithin A and UAS03 after the development of colitis reverses the condition and administration prior to development of colitis prevents it from occurring.”

The research was published in the journal Nature Communications.

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Rajbir Singh et al. 2019. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nature Communications 10, article number: 89; doi: 10.1038/s41467-018-07859-7