A metabolite found in pomegranates may help prevent colorectal cancer.
Researchers investigated the effects of a metabolite called urolithin A on colorectal cancer. Urolithin A is the result of gut bacteria metabolizing a type of polyphenol found in pomegranates. They found that the metabolite limits tumor growth and acts synergistically with immunotherapy.
The researchers noted that further research is needed to better understand the underlying mechanisms.
Colorectal cancer is the third most commonly diagnosed cancer globally. A patient’s chances of survival can be predicted by their "immunoscore", which is calculated from the density of cell-death-inducing cells (CD8+ cells) inside tumors.
Recent studies show that concentrated forms of urolithin A (UA), a natural product of pomegranate digestion, induce mitophagy — the breakdown of old or redundant “cellular powerhouses” known as mitochondria. In turn, this encourages the creation of new mitochondria and slows the progression of age-related diseases.
Other studies have found that UA has immunomodulatory effects in cells that reduce inflammation alongside cells that enhance immune function. Further study of the effects of UA on immune function could lead to the development of anti-tumor treatments.
Boosting the immune response
Recently, researchers explored the effects of UA on colorectal cancer in mice. They found that UA induced “strongly protective” anti-tumor T cell immunity in mice both when consumed in food and when used alongside CAR-T cell therapy, a treatment in which T cells — a type of immune cell — are altered to attack cancer cells.
The findings focus on the immune response which is where reliable therapeutic approaches are still lacking in the reality of colorectal cancer patients. By possibly improving the combination therapy with existing immunotherapies, the study opens up meaningful possibilities for further application in the clinic.
How does UA emerge?
UA is a metabolite of polyphenols. Polyphenols are known to have antioxidant and anti-inflammatory properties. The polyphenols are predominantly found in pomegranates but also strawberries, raspberries, and various nuts, especially walnuts.
Additionally, these foods contain a plethora of nutrients and bioactive molecules that are broadly beneficial for overall health. UA is converted by gut bacteria. Therefore, one must have a diverse gut microbiome to allow for this conversion to take place
This study suggests that beyond the expected general anti-inflammatory properties that UA has, it may also allow for greater immunomodulation wherein the body can detect and manage early tumor growths in the gastrointestinal tract, like those seen in colorectal cancer.
The researchers next examined the effects of UA on human T cells from five donors. Although it was observed in vitro, (meaning either a test tube, petri dish, etc.) UA was shown to have the capability to induce CD4 memory T cell production. This function allows for a rapid response in the event of re-exposure to an antigen- in this case, those would be tumor-specific antigens.
In other experiments, the researchers found that UA may also increase the efficacy of CAR-T cell therapy, a promising new immunotherapy to treat colorectal cancer.
The Pomegranate - A Nutritional Powerhouse
In addition to possessing anti-cancer properties, pomegranates also offer additional benefits. Pomegranates are low in calories, but high in fiber, vitamins, and minerals.
Antioxidants are compounds that help protect the cells of your body from damage caused by free radicals. Free radicals are always present in your body, however having too many of them can be harmful and contribute to a number of chronic diseases.
Pomegranates are rich in antioxidants and polyphenolic compounds that offer protection from this damage. The main bioactive compounds with antioxidant activity that are found in pomegranates are called punicalagins, anthocyanins, and hydrolysable tannins.
Eating pomegranates may help prevent the chronic inflammation associated with increased chronic disease risk. This is largely attributed to compounds called punicalagins, which have been shown to have antioxidant and anti-inflammatory properties in test-tube and animal studies.
Some human studies have also found that consuming pomegranate juice can reduce markers of inflammation in the body.
Test-tube studies have found that pomegranate extract may reduce oxidative stress and inflammation in the arteries, lower blood pressure, and help fight atherosclerosis — plaque buildup in the arteries that can lead to heart attacks and strokes.
In one human study, people with heart disease were given 1 cup (220 mL) of pomegranate juice daily for 5 days. The juice significantly reduced the frequency and severity of chest pain, as well as certain biomarkers in the blood that suggest a protective effect on heart health.
The polyphenols in pomegranates may increase exercise endurance, the length of time you’re able to partake in a physical activity before getting tired. One human study found that taking just 1 gram of pomegranate extract 30 minutes before running increased the time to exhaustion by 12%.
Other human research has found that pomegranate supplements have the potential to improve both exercise endurance and muscle recovery.