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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., Objectives: 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., Methods: 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., Results: 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., Conclusions: These findings illustrate the complex interplay between diet and aging in shaping the gut microbiota, potentially contributing to age-related disease., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Obesity is a risk factor for colorectal cancer (CRC), and alterations in the colonic microbiome and metabolome may be mechanistically involved in this relationship. The relative contribution of diet and obesity per se are unclear. We compared the effect of diet- and genetically-induced obesity on the intestinal microbiome and metabolome in a mouse model of CRC. Apc1638N mice were made obese by either high fat (HF) feeding or the presence of the Leprdb/db (DbDb) mutation. Intestinal tumors were quantified and stool microbiome and metabolome were profiled. Genetic obesity, and to a lesser extent HF feeding, promoted intestinal tumorigenesis. Each induced distinct microbial patterns: taxa enriched in HF were mostly Firmicutes (6 of 8) while those enriched in DbDb were split between Firmicutes (7 of 12) and Proteobacteria (5 of 12). Parabecteroides distasonis was lower in tumor-bearing mice and its abundance was inversely associated with colonic Il1b production (p<0.05). HF and genetic obesity altered the abundance of 49 and 40 fecal metabolites respectively, with 5 in common. Of these 5, adenosine was also lower in obese and in tumor-bearing mice (p<0.05) and its concentration was inversely associated with colonic Il1b and Tnf production (p<0.05). HF and genetic obesity differentially alter the intestinal microbiome and metabolome. A depletion of adenosine and P.distasonis in tumor-bearing mice could play a mechanistic role in tumor formation. Adenosine and P. distasonis have previously been shown to be anti-inflammatory in the colon and we postulate their reduction could promote tumorigenesis by de-repressing inflammation.

Obesity is a risk factor for colorectal cancer (CRC), and alterations in the colonic microbiome and metabolome may be mechanistically involved in this relationship. The relative contribution of diet and obesity per se are unclear. We compared the effect of diet- and genetically-induced obesity on the intestinal microbiome and metabolome in a mouse model of CRC. Apc1638N mice were made obese by either high fat (HF) feeding or the presence of the Leprdb/db (DbDb) mutation. Intestinal tumors were quantified and stool microbiome and metabolome were profiled. Genetic obesity, and to a lesser extent HF feeding, promoted intestinal tumorigenesis. Each induced distinct microbial patterns: taxa enriched in HF were mostly Firmicutes (6 of 8) while those enriched in DbDb were split between Firmicutes (7 of 12) and Proteobacteria (5 of 12). Parabecteroides distasonis was lower in tumor-bearing mice and its abundance was inversely associated with colonic Il1b production (p<0.05). HF and genetic obesity altered the abundance of 49 and 40 fecal metabolites respectively, with 5 in common. Of these 5, adenosine was also lower in obese and in tumor-bearing mice (p<0.05) and its concentration was inversely associated with colonic Il1b and Tnf production (p<0.05). HF and genetic obesity differentially alter the intestinal microbiome and metabolome. A depletion of adenosine and P.distasonis in tumor-bearing mice could play a mechanistic role in tumor formation. Adenosine and P. distasonis have previously been shown to be anti-inflammatory in the colon and we postulate their reduction could promote tumorigenesis by de-repressing inflammation. [ABSTRACT FROM AUTHOR]