Dried Plums Modify the Colon Luminal Metabolome in a Rat Model of Colon Carcinogenesis
Authors: Seidel Derek V , Taddeo Stella S , Azcarate‐Peril M Andrea , Carroll Raymond J , Turner Nancy D 
Published: November 2023

Diet is known to alter metabolism and composition of colon microbiota, which has important implications for disease prevention and treatment. We have shown that rats consuming a diet containing dried plums (PD, 5% of calories) have different abundances of major bacterial phyla throughout the colon, but most notably in the distal colon, compared to rats consuming a control diet (CD). Furthermore, PD rats had fewer precancerous colon cancer lesions (i.e. aberrant crypt foci) and lower fecal short chain fatty acid concentrations. Based on these observations, we sought to characterize the metabolome from the proximal and distal colon contents of these rats. Male Sprague‐Dawley rats were provided either CD (n=25) or PD (n=26) for 3 wk before receiving two injections of azoxymethane (AOM, 15 mg/kg BW, 7 d apart) or saline, and sacrificed 8 wk later. Luminal contents from the proximal and distal colon were used to conduct non‐targeted metabolomics profiling using multi‐platform, mass spectrometry techniques (Metabolon, Durham, NC). The analyses revealed numerous differences in the relative concentrations of biochemicals based on colon location (349 compounds, q≤0.05) and diet (121 compounds, q≤0.05). Additionally, 35 compounds were found to be different as a result of the interaction between diet and location (p≤0.05). Several biochemicals identified in the PD animals that were not detected in CD animals are endogenous to dried plums, including sugar alcohols and sugar‐derived metabolites (e.g., mannitol/sorbitol and 5‐hydroxymethylfurfural, q=0.000 for both), and plant‐associated compounds (e.g., quinate, salicylate, gentisate, and sinapate, q<0.000 for all). Furthermore, PD animals had increases in microbially‐derived metabolites, including enterolactone, enterodiol, hippurate, and 2‐oxindole‐3‐acetate (q<0.000 for all). Although bioactive functions have been ascribed to the individual compounds identified in PD animals, consumption of the whole fruit permits delivery of a unique combination of dried plum bioactives to the colon. The potential for enhanced bioefficacy of PD bioactives when administered in combination warrants further study. Investigations using other experimental models of colon cancer will be essential to better characterize the protective mechanisms of PD consumption on colon health. Nevertheless, these data demonstrate the efficacy of dried plums to directly (via endogenous biochemicals) and indirectly (via microbially‐derived biochemicals) alter the colon luminal metabolome, which may have contributed to the reduction in colon carcinogenesis in this model. Our previously reported alterations in the composition of microbiota throughout the colon of PD rats and suppression of colon cancer lesions in concert with the alterations in microbially‐derived metabolites reported here support the identity of dried plums as a prebiotic food. Importantly, the effects of dried plum consumption on the colon microbiota and metabolism are seen at level that contributes only 5% of total diet calories, which is equivalent to the recommended 100 calorie, 40 g serving of dried plums in a human diet.Support or Funding InformationSupported by California Dried Plum Board PN 12–20.