Evaluation of PTSO delivery approaches for gut microbiota modulation in colorectal cancer: A comparative study of microcapsules containing Allium derivatives

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with gut microbiota modulation emerging as a critical factor in its development. Propyl propane thiosulfonate (PTSO), an organosulfur compound derived from Allium species, has shown potential as a therapeutic agent for CRC due to its antioxidant and anti-inflammatory properties. This study evaluated three PTSO delivery systems (dextrin, pectin microcapsules, and hydroxypropyl methylcellulose capsules) designed to enhance bioavailability and protect PTSO through digestion. We assessed their antioxidant capacity, cytotoxic effects on CRC cells, and impact on short-chain fatty acid (SCFA) production and gut microbiota composition after in vitro digestion and fermentation with feces of healthy individuals and CRC patients. Results demonstrated that each formulation displayed distinct release profiles and antioxidant activities post-digestion and fermentation, with microencapsulated PTSO showing superior stability, bioavailability and the highest antitumoral efficacy in CRC cell lines, achieving an IC50 value of 20.5 μM. Significant differences in SCFA production and gut microbiota modulation were observed across the formulations. Although further in vivo studies are needed to validate these findings and understand long-term effects, PTSO shows promise as a bioactive compound within functional nutrition. Its ability to modulate gut microbiota composition, alongside its enhanced bioavailability through innovative delivery systems, suggests that PTSO could play a key role in the development of dietary strategies aimed at reducing CRC risk and progression. • Innovative PTSO delivery systems enhance bioavailability and stability during digestion. • Microencapsulated PTSO demonstrated superior antioxidant capacity and cytotoxic effects in CRC cells • PTSO formulations significantly modulated gut microbiota composition, particularly SCFA production. • Distinct release profiles and microbiota effects highlight the importance of delivery system design. • PTSO shows potential as a bioactive compound for functional foods targeting CRC prevention.