Shaping Functional Gut Microbiota Using Dietary Bioactives to Reduce Colon Cancer Risk
Abstract
Alterations in gut microbiota and metabolome occur during colon carcinogenesis and metabolic syndrome, but these changes may be reduced by exposure to bioactive compounds in foods. We hypothesized that bioactive compound-rich diets improve colon microbiota and metabolism to mitigate: 1) azoxymethane- (AOM) induced colon carcinogenesis in rats, 2) HZE radiation-induced alterations in the microbiota in mice, and 3) risk factors that define metabolic syndrome in human subjects.
A dried plum (DP) containing diet reduced preneoplastic lesions and led to lower Nos2, Tlr2 and Tlr4 expression than basal diet counterparts. DP increased Bacteroidetes and decreased Firmicutes in the distal colon, and increased Actinobacteria and decreased Lactobacillus throughout the colon. DP reduced fecal short chain fatty acid (SCFA) concentrations and increased luminal concentrations of compounds derived from microbial metabolism of plant derivatives. Microbial metagenome prediction revealed alterations in KEGG pathways related to metabolism and pathway analysis of distal metabolites suggests DP altered critical regulators of colon carcinogenesis and inflammation.
Exposure to 1 Gy of Fe (RAD) did not affect luminal SCFA, however, DP+RAD mice had a lower percentage of propionate compared to DP+SHAM, control diet (CD)+SHAM and CD+RAD groups. RAD increased the abundance of Akkermansia; however, DP increased Akkermansia, Lachnospiraceae, Anaeroplasma, and Coriobacteriaceae and reduced Oscillospira, Ruminococcaceae, Lactobacillus, and Clostridiaceae. Evidence of an interaction between DP and radiation exposure in 40% of animals warrants further investigation.
Sumac sorghum (SS) increased the anti-inflammatory genus Faecalibacterium, but had no effect on serum markers of inflammation, blood lipids, fasting blood sugar, percentage body fat, or fecal SCFA. Metabolomics of plasma showed an increase in 3-hydroxyhippurate following SS consumption, and a reduction of three gamma-glutamyl AAs. Targeted fecal metabolite quantification revealed increased concentrations of 3-(3-hydroxyphenol)propionic, 3-phenylpropionic, and benzoic acid, and reduced quinic acid following 100 g/day SS consumption. Correlation between plasma metabolites and fecal microbes revealed hippurate was positively correlated with Akkermansia, while Faecalibacterium was negatively associated with several gamma-glutamyl amino acids.
Both DP and SS modified the colon metabolome and microbiome, increased putatively beneficial bacteria and microbially-derived compounds associated with positive health outcomes.
Causal investigations and interactions between the DP and radiation are warranted.
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Citation
Seidel, Derek Vaughn (2019). Shaping Functional Gut Microbiota Using Dietary Bioactives to Reduce Colon Cancer Risk. Doctoral dissertation, Texas A & M University. Available electronically from https : / /hdl .handle .net /1969 .1 /183852.