Abstract 4228: Replacing red and processed meat with legumes modulates gut microbiome and microbiota-related metabolites linked to gut health and cancer prevention in healthy working-aged men

Background and Aim: Changing dietary habits have great potential for colorectal cancer (CRC) prevention. Regardless of the accumulated evidence on the relationship between dietary protein sources and CRC, the explaining mechanisms remain not well established. Diet-delivered microbial metabolites such as secondary bile acids (BA), N-nitroso compounds (NOC), trimethylamine N-oxide (TMAO), short-chain fatty acid (SCFA), and branched-chain fatty acids (BCFA) have been suggested to mediate the relationship. The aim of this study was to examine the effects of partial replacement of red and processed meat (RPM), associated with higher CRC risk, with legumes on the fecal microbiota composition and metabolite profiles in healthy men. Methods: The study was a partly controlled 6-wk parallel design randomized clinical trial (n=102, age 37 y (range 21 - 61 y), BMI 25.5 ± 3.3 kg/m2) with two groups following either a diet supplemented with RPM (meat group) or a diet supplemented with legumes and RPM (legume group). The amount of RPM (200 g/wk) in the legume group was based on the maximum amount recommended by the EAT-Lancet Commission whereas the amount in the meat group (760 g/wk) corresponded the average intake of Finnish men. Fecal SCFAs (µg/ml) and BCFAs (µg/ml) were analyzed with GS-MS, BAs (arbitrary, analyte/standard ratios) with UHPLC-MS/MS, and NOCs (pmol/mg) with selective de-nitrosation and chemiluminescence-based detection. Urine TMAO was quantified by NMR and fecal microbiota composition was analyzed using 16S rRNA amplicon sequencing techniques. Dietary intakes were analyzed with 4-day food records. Results: At the baseline, no significant differences (p > 0.05) were reported in age, BMI, dietary intake of total fiber (g/d), protein (E%), fat (E%), or in the fecal metabolites. The legume group had more pronounced effects on the gut microbiota community level, indicating ecosystem level differences. Total NOCs (p < 0.0001) and heme-originated NOCs (FeNO; p < 0.0001) were smaller in the legume group than in the meat group. Significant differences between the groups were observed in intake of total fiber (p < 0.001), cholesterol (mg/d, p < 0.001), saturated (p < 0.005), and polyunsaturated fat (p < 0.001). Although not significant (p > 0.05), total, secondary and unconjugated BAs, and total BCFA were higher in the meat group, whereas primary and conjugated BAs and total SCFAs were higher in the legume group. The concentration of total SCFA and individual SCF