(P21-011-24) Impact of a High-Legume Weight-Reduction Diet on the Plasma Metabolome in Adults With Overweight/Obesity With a History of Colorectal Polyps: A Pilot Study

Objectives: We characterized the impact of a high-fiber weight-loss diet based on legumes (HLD) vs. a low-fiber weight-loss control diet on plasma metabolomic pathways in overweight/obese men with a history of benign colorectal polyps.

Methods: Participants (40-75 yrs old, BMI of 25-40 kg/m²) were given an HLD diet (n=7) or an isocaloric weight-loss diet without added legumes (n=5; control) for 8 weeks. Entrées for lunch and dinner with dietary guidance were provided to each group, designed to achieve weight loss of 0.5-1.0 kg/wk. Legume and control entrées were matched for total energy and macronutrient profiles. The dietary fiber goal for the HLD diet group was 40g/day, and for the control group was 20g/day. Whole gut transit time (WGTT) was determined during week 8. Untargeted plasma high-resolution metabolomics was conducted using dual-mode liquid chromatography mass spectrometry (LC/MS) at baseline and after 8 weeks. Plasma metabolite changes between diet groups over 8 weeks and the interaction with WGTT were assessed using metabolome-wide association studies (MWAS) via a generalized linear model with pathway enrichment analysis.

Results: The difference between week 8 and baseline metabolites revealed 13,484 C18 LC column and 21,677 HILIC LC column features for analysis. A total of 789 (C18) and 651 (HILIC) metabolites differed by group over time (p  < 0.05), respectively. Metabolic pathways that were significantly altered in the HLD group vs. the control group included de novo fatty acid and polyunsaturated fatty acid (PUFA) biosynthesis, bile acid biosynthesis, and linoleate, vitamin D3, arginine, and proline metabolism. WGTT was similar between groups at week 8. However, WGTT modified the association of diet with the plasma metabolome, revealing different metabolic pathways, including those associated with leukotriene, glycerophospholipid, and amino acid (alanine, glycine, methionine and cysteine, serine, and threonine) metabolism.

Conclusions: In overweight/obese adult men with a history of benign colorectal polyps, the HLD diet given for 8 weeks significantly impacted lipid, bile acid, vitamin D, and amino acid metabolic pathways compared to men receiving the low fiber control weight loss diet. Gut transit time modified the effects of the HLD diet on plasma metabolites and metabolic pathways.

Funding Sources: National Institutes of Health. No # allowed.