SCOPE: Urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and ellagic acid (EA). We investigated whether urolithins could be detected in colon tissues from colorectal cancer (CRC) patients after pomegranate extract (PE) intake. METHODS AND RESULTS:CRC patients (n = 52) were divided into controls and PEs consumers (900 mg/day for 15 days) before surgical resection. PEs with low (PE-1) and high (PE-2) punicalagin:EA ratio were administered. Twenty-three metabolites, but no ellagitannins, were detected in urine, plasma, normal (NT) or malignant (MT) colon tissues using UPLC-ESI-QTOF-MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole TOF). Free EA, five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues. Individual and total metabolites levels were higher in NT than in MT, independently of the PE consumed. The maximal mean concentration (1671 ± 367 ng/g) was found in NT after consumption of PE-1 and the lowest concentration (42.4 ± 10.2 ng/g) in MT with PE-2. Urolithin A or isourolithin A were the main urolithins produced (54 and 46% patients with urolithin A or isourolithin A phenotype, respectively). High punicalagin content (PE-2) hampered urolithins formation. CONCLUSION: Significant levels of EA derivatives and urolithins are found in human colon tissues from CRC patients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.
RCT Entities:
SCOPE: Urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and ellagic acid (EA). We investigated whether urolithins could be detected in colon tissues from colorectal cancer (CRC) patients after pomegranate extract (PE) intake. METHODS AND RESULTS:CRCpatients (n = 52) were divided into controls and PEs consumers (900 mg/day for 15 days) before surgical resection. PEs with low (PE-1) and high (PE-2) punicalagin:EA ratio were administered. Twenty-three metabolites, but no ellagitannins, were detected in urine, plasma, normal (NT) or malignant (MT) colon tissues using UPLC-ESI-QTOF-MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole TOF). Free EA, five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues. Individual and total metabolites levels were higher in NT than in MT, independently of the PE consumed. The maximal mean concentration (1671 ± 367 ng/g) was found in NT after consumption of PE-1 and the lowest concentration (42.4 ± 10.2 ng/g) in MT with PE-2. Urolithin A or isourolithin A were the main urolithins produced (54 and 46% patients with urolithin A or isourolithin A phenotype, respectively). High punicalagin content (PE-2) hampered urolithins formation. CONCLUSION: Significant levels of EA derivatives and urolithins are found in human colon tissues from CRCpatients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.
Authors: Tulasigeri M Totiger; Supriya Srinivasan; Venkatakrishna R Jala; Purushottam Lamichhane; Austin R Dosch; Alexander A Gaidarski; Chandrashekhar Joshi; Shobith Rangappa; Jason Castellanos; Praveen Kumar Vemula; Xi Chen; Deukwoo Kwon; Nilesh Kashikar; Michael VanSaun; Nipun B Merchant; Nagaraj S Nagathihalli Journal: Mol Cancer Ther Date: 2018-11-07 Impact factor: 6.261
Authors: Dongryeol Ryu; Laurent Mouchiroud; Pénélope A Andreux; Elena Katsyuba; Norman Moullan; Amandine A Nicolet-Dit-Félix; Evan G Williams; Pooja Jha; Giuseppe Lo Sasso; Damien Huzard; Patrick Aebischer; Carmen Sandi; Chris Rinsch; Johan Auwerx Journal: Nat Med Date: 2016-07-11 Impact factor: 53.440
Authors: Peter Spanogiannopoulos; Elizabeth N Bess; Rachel N Carmody; Peter J Turnbaugh Journal: Nat Rev Microbiol Date: 2016-03-14 Impact factor: 60.633