(OR14-07-24) Resistant Starches From Dietary Pulses Distinctly Modulate the Gut Microbiome, Mycobiome, Metabolome, and Neurocognitive Function in Aging Mice

Objectives: To investigate how resistant starch (RS) from different dietary pulses influence gut microbiome, mycobiome, metabolome, and neurocognitive function in 60-weeks old mice harboring a humanized microbiome.

Methods: C57B6/J mice transplanted with human gut microbiome were fed for 20 weeks: western-style high-fat diet (control; 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; fiber control). 16S rRNA-based microbiome sequencing, ITS-based mycobiome sequencing, and NMR-based global metabolomics were performed on fecal samples. Open-field and T-maze tests were performed on mice to assess neurocognitive function. mRNA expression assays were performed on hypothalamus tissues to assess markers of tight-junctions, senescence, and inflammatory arrays.

Results: RS had unique impacts on the gut microbiome, mycobiome, and metabolome, with pronounced changes noted in LEN and CKP groups. RS intervention induced significant changes in gut microbiome diversity, with no notable alterations in the mycobiome. At phylum level, relative abundance of Firmicutes and Basidiomycota increased in LEN group, whereas Bacteroidota and Anthophyta increased in CKP group. Bacterial genus Dubosiella increased, while fungal genus Candida decreased in both groups compared to CTL. Beneficial metabolites like lactate and butyrate increased in both groups. Machine-learning analysis identified the microbial taxa with the highest scores for group discrimination, including bacterial taxa (Faecalibaculum, Lactococcus, and Dubosiella) and fungal taxa (Candida, Penicillium, and Nakazawaea). RS intervention ameliorated the inflammatory state in the hypothalamus by suppressing pro-inflammatory cytokines (IL8, IFNɣ) and reducing expression of senescence genes (p16, p21). LEN group demonstrated specific enhancements in learning memory and exploratory behavior.

Conclusions: This study underscores the potential of RS derived from dietary pulses as a promising prebiotic supplement for improving healthspan of aging population.

Funding Sources: United States Department of Agriculture