inflammatory bowel diseases

A recent study investigated the anti-inflammatory activities of metabolites found in berries and pomegranates. The findings may impact the treatment and prevention of inflammatory bowel diseases.

The inflammatory bowel diseases include ulcerative colitis and Crohn’s disease. These are autoimmune diseases that cause intestinal inflammation. In 2018, an estimated 270,000 Canadians were living with either ulcerative colitis or Crohn’s disease. Traditional therapy for inflammatory bowel diseases involves corticosteroids and drugs that suppress the immune system.

In recent years, studies have associated alterations in the bacterial environment in the intestine with certain diseases such as cancer and inflammatory bowel diseases. Researchers from the Department of Microbiology and Immunology at the James Graham Brown Cancer Center in Louisville, Kentucky designed a study to test the theory that certain bacterial metabolites can affect inflammatory bowel diseases. The results of this study were published in Nature Communications.

Urolithin A has shown anti-inflammatory, anti-oxidant, and anti-aging properties

The researchers chose a metabolite derived from berries and pomegranate that have previously shown health benefits in humans. Urolithin A is a metabolite of gut bacteria that originates from polyphenolic compounds found in berries and pomegranates. This metabolite has previously shown anti-inflammatory activities and anti-oxidant and anti-aging properties. In further analyses of this metabolite, the researchers aimed to demonstrate that Urolithin A also has beneficial effects on gut barrier function through specific physiological pathways.

In vitro and in vivo experiments were performed on mice to demonstrate the beneficial effects of Urolithin A on inflammatory bowel diseases. Consistent with previous research, Urolithin A demonstrated a reduction in the release of the inflammation factors interleukin 6 and tumour necrosis factor alpha in mice immune cells. In vivo, treatment with Urolithin A reduced the inflammatory response in the blood of a mouse model of peritonitis.  These tests suggest that Urolithin A has potent anti-inflammatory activities.

Metabolites close to the gut lining may affect intestine permeability

The researchers also theorized that because the metabolites are in such close proximity to the lining of the gut that they may have effects on the permeability of the intestine. The permeability of the bowel is maintained by tight junction proteins. Through further in vitro studies, the researchers found that intestinal cells treated with Urolithin A produced a large number of tight junction proteins that could preserve the barrier of the gut. In vivo, the researchers also found high levels of tight junction proteins in the colons of mice treated with Urolithin A.

The purpose of this study was to demonstrate the effect of metabolites of gut bacteria on inflammatory bowel diseases. The researchers examined the effect of oral treatment of Urolithin A in a mice model of colitis. The mice exposed to 2,4,6-Trinitrobenzenesulfonic acid (TNBS acid) develop colitis. Once treated with Urolithin A, these mice experienced a protective effect from various inflammatory bowel disease symptoms such as body weight loss and increased permeability of the gut. These mice also exhibited a lower disease activity index score. A decreased colon shortening and a reduced weight to length ratio were also observed, which supports the role of Urolithin A on decreasing colon inflammation.

Possible protective effects against inflammatory bowel diseases

The preventative effect of Urolithin A on gut health was also studied. Normal mice were pretreated with Urolithin A before they were exposed to the inflammatory bowel disease inducer TNBS acid. The researchers noted a preventative effect against colon shortening and colon inflammation. An enhanced gut barrier function was also observed. These last two studies on the impact of Urolithin A on inflammatory bowel diseases in mice reveals the protective effects of the gut metabolite in vivo.

In conclusion, throughout the various studies performed on healthy and diseased mice, this research suggests a possible health benefit of the gut metabolite Urolithin A. The in vitro and in vivo studies were consistent with past research.

This analysis went beyond confirming previous research and determined the mechanisms of action and the physiological pathways that explain the benefits of Urolithin A on inflammatory bowel diseases. These benefits may be efficacious in preventing and treating inflammatory bowel diseases and perhaps other disorders. Further research is necessary to explore the effects of gut metabolites on inflammatory bowel diseases in humans.

Written by Jessica Caporuscio, PharmD

References:

  1. Crohn’s and Colitis Canada. The 2018 Impact of Inflammatory Bowel Disease in Canada Report, and Crohn’s and Colitis Awareness Month. http://crohnsandcolitis.ca/News-Events/News-Releases/The-2018-Impact-of-Inflammatory-Bowel-Disease-in-C
  2. Idriss HT, Naismith JH. TNF alpha and the TNF receptor superfamily: structure-function relationship(s) [abstract]. Microsc Res Tech. 2000.
  3. Seemann S, Zohles F, Lupp A. Comprehensive comparison of three different animal models for systemic inflammation. J. Biomed. Sci. 2017.
  4. Singh R, Chandrashekharappa S, Bodduluri SR, et al. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nat Commun. 2019.
  5. Tanaka, T., Narazaki, M., & Kishimoto, T. IL-6 in inflammation, immunity, and disease. Cold Spring Harbor perspectives in biology. 2014.
  6. Walfish AE. Overview of Inflammatory Bowel Disease. Merck Manual Professional Version. 2017. https://www.merckmanuals.com/en-ca/professional/gastrointestinal-disorders/inflammatory-bowel-disease-ibd/overview-of-inflammatory-bowel-disease?query=inflammatory%20bowel%20disease
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