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- 10/12/2023

The Evolution of a Therapeutic Approach: Polyphenols to Clinical Strategies for IBS

AgroFOOD Industry Hi Tech

Irritable Bowel Syndrome (IBS) is a challenging gastroenterological condition often accompanied by psychological comorbidities. Polyphenols, with their antioxidant and anti-inflammatory properties, are emerging as a potential IBS treatment by modulating gut microbiota. Specifically, punicalagin, found in pomegranate extracts, transforms into ellagic acid, enhanced by probiotics. A clinical study at the University Hospital of Caceres found that combining probiotics and punicalagin-rich pomegranate extract for one month significantly improved bowel function and psychological well-being in IBS patients, with notable pain reduction and improved mood. This approach holds promise in addressing IBS and its associated psychological distress. 


Irritable Bowel Syndrome (IBS) poses a perplexing challenge in gastroenterological medicine, often accompanied by psychological comorbidities, including anxiety and depression. While the medical community has explored various treatment avenues, the modulation of gut microbiota through natural substances like polyphenols is gaining recognition. An intriguing possibility tested in an in-vitro study (1) involved combining an ellagitannin (ET) rich pomegranate extract (Pomanox®, Punicalagin 200) with probiotics to boost their biotransformation. This combination’s potential was further explored in a clinical study focused on IBS, a condition heavily influenced by the gut-brain axis, with preliminary findings presented at the LXXXII Congress of The Spanish Society of Digestive Pathology (SEPD) in Seville, Spain (2). 

Polyphenols have become a captivating research focus primarily due to their antioxidant and anti-inflammatory properties. Their role as a novel class of prebiotic substrates stems from their metabolic compatibility with intestinal microbiota. Among these, punicalagin, an ellagitannin found in pomegranate extracts, has shown particularly compelling results. An in-vitro investigation revealed punicalagin’s low bioavailability but significant biochemical transformation into ellagic acid (EA), which exhibits higher gut absorption and bioactivity. Probiotic bacteria further enhanced this biotransformation. EA’s functions extend beyond protecting against oxidative stress to modulating crucial cellular signaling pathways, especially those linked to inflammation and aging. 

The evidence from the in-vitro study paved the way for a clinical research hypothesis: Could the concurrent administration of probiotics and punicalagin-rich pomegranate extract synergistically improve both gut function and psychological well-being in IBS patients? 


Clinical Study and Preliminary Findings 

To test this hypothesis, the University Hospital of Caceres conducted a double-blind study. Eighteen patients who met the Rome IV criteria for IBS were randomly assigned to either the Treated (T) or Placebo (P) groups. The T group received a one-month regimen of probiotics and punicalagin-rich pomegranate extract. The results were clear: the T group exhibited significant improvements in bowel function and psychological well-being compared to the P group. Specifically, seven out of the nine treated patients reported a statistically significant reduction in pain related to bowel movements (p<0.05). They also reported improved mood, further validating the dual-action hypothesis. 

The preliminary clinical data suggest that this combination has yielded promising outcomes, particularly in the biosynthesis of bioactive metabolites like ellagic acid and urolithins, which seem pivotal in enhancing the functionality of the gut-brain axis. 



  1. Clinical response of adult patients with irritable bowel syndrome using gut-brain-axis modulation: preliminary results of a double-blind placebo study. Presented at the LXXXII Congress of The Spanish Society of Digestive Pathology (SEPD), Seville (Spain) June 8 to 10, 2023
  2. Biodegradation of Punicalagin into Ellagic Acid by Selected Probiotic Bacteria: A Study of the Underlying Mechanisms by MS-Based Proteomics. Caballero, v. et al. Journal of Agricultural and Food Chemistry 2022 70 (51), 16273-16285. DOI: 10.1021/acs.jafc.2c06585 


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