(P02-026-23) Multi-Omics Analyses Reveal Prebiotic Effects of Dietary Pulses-Derived Resistant Starches on Aging-Associated Gut and Metabolic Health in a Humanized Murine Model

Objectives: To investigate the prebiotic mechanisms of dietary pulses-derived resistant starch (RS) in modulating the gut microbiome, metabolome, and metabolic health in 60-weeks old mice carrying human gut microbiome.

Methods: Fecal microbiota transplanted C57B6/J mice were fed for 20 weeks with either a western-style high-fat diet (CTL) or CTL diet supplemented (5% w/w) with RS from pinto beans (PTB), black-eyed-peas (BEP), lentils (LEN), chickpeas (CKP), or inulin (INU). Illumina-based 16S rRNA gene sequencing and NMR-based untargeted metabolomics were performed on fecal samples. Glycemic response, insulin sensitivity, and gut permeability were assessed using meal tolerance, insulin tolerance and FITC-dextran tests, respectively. Gene expression analysis for intestinal inflammatory markers and tight junction proteins was measured using ΔΔCt method.

Results: RS supplementation induced distinct and sex-specific modulations in gut microbiome-metabolome arrays. Firmicutes were enriched and Proteobacteria depleted in LEN, while Bacteroidota were promoted by CKP and INU. Machine-learning analysis revealed RS-mediated reduced proportion of opportunistic genera (Enterococcus, Odoribacter, Alistipes, and Desulfovibrio). Notably, butyrate was increased by LEN and CKP, while propionate by INU. Amino acid and bile acid metabolism were positively altered by RS groups with suppression of choline-to-trimethylamine by LEN and CKP. Broadly, microbiome-metabolome correlation revealed abundance of beneficial metabolites with Dubosiella, Bacteroides, Parasutterella, and Parabacteroides, and harmful metabolites with Bilophila, Colidextribacter, Faecalibaculum, Enterococcus, and Odoribacter. Additionally, RS mitigated adverse metabolic outcomes viz., postprandial glycemia, gut hyperpermeability and pro-inflammatory responses.

Conclusions: The study highlights the prebiotic effects of dietary pulses-derived resistant starch, which could help in addressing ‘dietary fiber gap’ of growing elderly population and could also be useful for functional foods and nutritional applications for improved gut health.

Funding Sources: This work was supported by funding from the Pulse Crop Health Initiative program of the United States Department of Agriculture (USDA-ARS).