Aging Modulates the Effect of Dietary Glycemic Index on Gut Microbiota Composition in Mice

Gut microbiome composition profoundly impacts host physiology and is modulated by several environmental factors, most prominently diet. The composition of gut microbiota changes over the lifespan, particularly during the earliest and latest stages. However, we know less about diet-aging interactions on the gut microbiome. We previously showed that diets with different glycemic indices, based on the ratio of rapidly digested amylopectin to slowly digested amylose, led to altered composition of gut microbiota in male C57BL/6J mice.

Here, we examined the role of aging in influencing dietary effects on gut microbiota composition and aimed to identify gut bacterial taxa that respond to diet and aging.

We studied 3 age groups of male C57BL/6J wild-type mice: young (4 mo), middle-aged (13.5 mo), and old (22 mo), all fed either high glycemic (HG) or low glycemic (LG) diets matched for caloric content and macronutrient composition. Fecal microbiome composition was determined by 16S rDNA metagenomic sequencing and was evaluated for changes in α- and β-diversity and bacterial taxa that change by age, diet, or both.

Young mice displayed lower α-diversity scores than middle-aged counterparts but exhibited more pronounced differences in β-diversity between diets. In contrast, old mice had slightly lower α-diversity scores than middle-aged mice, with significantly higher β-diversity distances. Within-group variance was lowest in young, LG-fed mice and highest in old, HG-fed mice. Differential abundance analysis revealed taxa associated with both aging and diet. Most differential taxa demonstrated significant interactions between diet and aging. Notably, several members of the Lachnospiraceae family increased with aging and HG diet, whereas taxa from the Bacteroides_H genus increased with the LG diet. Akkermansia muciniphila decreased with aging.

These findings illustrate the complex interplay between diet and aging in shaping the gut microbiota, potentially contributing to age-related disease.