Diet And Aging Influence The Dynamic Of The Gut Microbiome And Health In Mice

Abstract

The aging population and age-related diseases are a growing issue in Australia. Promoting healthy aging delays disease onset, improving quality of life and reducing healthcare costs. Diet impacts metabolic health and lifespan through gut microbiota, with age-related decline linked to chronic inflammation and immune dysfunction. This "inflammaging" and "immuno-senescence" can be understood by considering diet and the microbiome alongside immuno-metabolic health.

This thesis combines data from cross-sectional, longitudinal, and gnotobiotic animal models to examine the interactions between diet, the gut microbiome, and host physiological outcomes. Diet was categorized into three macronutrients: carbohydrate, protein, and fat. A geometric framework was used to explore microbiota status and microbial behavior under different nutrient environments during aging, with mechanistic links evaluated in the gnotobiotic model.

The common finding was that aging had impact on gut microbial composition. Two microbial types were identified: Type I, enriched with Bacteroidota and Verrucomicrobiota (Akkermansia), and Type II, high in Firmicutes and Actinobacteriota. Type I was associated with fat intake, while Type II correlated with carbohydrate intake. At the global community level, age-related microbial type shift from type II to type I was observed with different rates under different nutrient environments. Within the individual, distinct microbial state transitions were observed with varied onset ages subject to diet. Delaying the microbial state transition and microbial type drift might keep the health state of the microbiome and prolong the lifespan. Transferring aged gut microbiome to young germ-free mice resulted microbiome associated aging phenotype. However, the age’s impact was marginal compared to the diet.

Overall, this thesis presented the possibility of dietary intervention in slowing age-related decline and promoting healthy aging.