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Session: Diet-Gut Microbiome Interactions in Health and Disease (Oral 19)

(OR19-05-24) The Gut Microbiome Across the Murine Lifespan: Impact of Diet and Its Association With Inflammation, Lipids, Liver Cancer, and Lifespan

Monday, July 1, 2024
8:48 AM – 9:00 AM CT
Location:  W184
Objectives: We aimed to determine associations between the gut microbiome, cancer, lifespan and markers of health and disease in mice fed a low or high fat diet with or without fruits and vegetables (F&V).

Methods: Using a longitudinal study design, 5-week-old male C57BL/6J mice were randomized into one of four groups (n = 60/group): low-fat-control (LF-C, 10% kcal fat), high-fat-control (HF-C, 45% kcal fat), and each supplemented with 15% (w/w) of a unique F&V mixture (LF-FV and HF-FV). Gut microbiome richness and community structure were determined by α- and β-diversity, Shannon and Bray-Curtis respectively, at baseline, and 6-, 16-, and 21-months post-intervention. Differential abundance was determined by multivariable linear regression. Additionally, fecal short-chain fatty acids (SCFAs) were measure. To determine functional changes, a sub-set of mice were selected (n=5-6/group) for metagenomic analysis. Associations between microbiome, biomarkers, liver cancer and life span as influenced by age and diet were determined.

Results: Both age and diet significantly impacted the composition and function of the gut microbiome. F&V was associated with enrichment of SCFA-producing microbiota and were positively and significantly correlated with fecal butyrate and acetate concentrations. HF-C mice exhibited higher abundance levels of microbiota previously associated with obesity and liver diseases, such as non-alcoholic fatty liver and cancer. Importantly, F&V intake attenuated these effects. Longitudinal analysis revealed significant associations between bacteria and liver cancer incidence, pro-inflammatory cytokines, and blood lipids. Metagenomic analysis revealed that F&V was linked to a significant enrichment of gene families related to the metabolism of polyphenols and complex carbohydrates.

Conclusions: F&V shapes the aging gut microbiome by promoting the enrichment of bacterial genera associated with metabolism of plant-derived polyphenols and complex carbohydrates, which are inherently present in F&V at appreciable concentrations, and the production of SCFA. Moreover, F&V intake attenuates the enrichment of microbial signatures linked to liver cancer and obesity in the context of a high-fat diet.

Funding Sources: Supported by the U.S. Department of Agriculture—Agricultural Research Service (ARS), under Agreement No. 58-8050-9-004.