Gut microbiome and metabolome analyses reveal the protective effect of special high‐docosahexaenoic acid tuna oil on d‐galactose‐induced aging in mice

Aging is closely related to altered gut function and its microbiome composition. To elucidate the mechanisms involved in the preventive effect of special high‐docosahexaenoic acid tuna oil (HDTO) on senescence, the effects of different doses of HDTO on the gut microbiome and metabolome of d‐galactose‐induced aging mice were studied. Deferribacteres and Tenericutes and uridine might be used as indicator bacteria and characteristic metabolites to identify aging, respectively. HDTO markedly improved the impaired memory and antioxidant abilities induced by d‐galactose. At the phylum level, the abundance of Firmicutes and Tenericutes was significantly increased upon d‐galactose induction, while that of Bacteroidetes, Proteobacteria, and Deferribacteres was significantly decreased. At the genus level, the variation mainly presented as an increase in the abundance of the Firmicutes genera Ligilactobacillus, Lactobacillus, and Erysipelothrix, the decrease in the abundance of the Bacteroidetes genera Bacteroides and Alistipes, the Firmicutes genus Dielma, and the Deferribacteres genus Mucispirillum. HDTO supplementation reversed the alterations in the intestinal flora by promoting the proliferation of beneficial flora during the aging process; the metabolic pathways, such as glycine–serine–threonine metabolism, valine–leucine–isoleucine biosynthesis, and some metabolic pathways involved in uridine, were also partially restored. Furthermore, the correlation analysis illustrated an obvious correlation between gut microbiota, its metabolites, and aging‐related indices. Moreover, it is worth noting that the metabolic regulation by dietary intervention varied with different HDTO doses and did not present a simple additive effect; indeed, each dose showed a unique modulation mechanism.