ABSTRACT
BACKGROUND: 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. OBJECTIVE: Here, we examined the role of aging in influencing dietary effects on gut microbiota composition and to identify gut bacterial taxa that respond to diet and aging. METHODS: We studied three age groups of male C57BL/6J wild-type mice: young (4 months), middle-aged (13.5 months), and old (22 months), 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 alpha and beta diversity and bacterial taxa that change by age, diet, or both. RESULTS: Young mice displayed lower alpha diversity scores than middle-aged counterparts but exhibited more pronounced differences in beta diversity between diets. In contrast, old mice had slightly lower alpha diversity scores than middle-aged mice, with significantly higher beta 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, while taxa from the Bacteroides_H genus increased with the LG diet. Akkermansia muciniphila decreased with aging. CONCLUSIONS: These findings illustrate the complex interplay between diet and aging in shaping the gut microbiota, potentially contributing to age-related disease.
ABSTRACT
Infant fecal metabolomics can provide valuable insights into the associations of nutrition, dietary patterns, and health outcomes in early life. Breastmilk is typically classified as the best source of nutrition for nearly all infants. However, exclusive breastfeeding may not always be possible for all infants. This study aimed to characterize associations between levels of mixed breastfeeding and formula feeding, along with solid food consumption and the infant fecal metabolome at 1- and 6-months of age. As a secondary aim, we examined how feeding-associated metabolites may be associated with early life neurodevelopmental outcomes. Fecal samples were collected at 1- and 6-months, and metabolic features were assessed via untargeted liquid chromatography/high-resolution mass spectrometry. Feeding groups were defined at 1-month as 1) exclusively breastfed, 2) breastfed >50% of feedings, or 3) formula fed ≥50% of feedings. Six-month groups were defined as majority breastmilk (>50%) or majority formula fed (≥50%) complemented by solid foods. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant Development at 2 years. Changes in the infant fecal metabolome were associated with feeding patterns at 1- and 6-months. Feeding patterns were associated with the intensities of a total of 57 fecal metabolites at 1-month and 25 metabolites at 6-months, which were either associated with increased breastmilk or increased formula feeding. Most breastmilk-associated metabolites, which are involved in lipid metabolism and cellular processes like cell signaling, were associated with higher neurodevelopmental scores, while formula-associated metabolites were associated with lower neurodevelopmental scores. These findings offer preliminary evidence that feeding patterns are associated with altered infant fecal metabolomes, which may be associated with cognitive development later in life.
