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.

Dose effect of high-docosahexaenoic acid tuna oil on dysbiosis in high-fat diet mice.

BACKGROUND: The health benefits of tuna oil, which is different from the fish oil commonly studied, and its higher docosahexaenoic acid (DHA) content, have attracted much scientific attention in recent years. In this study, prepared tuna oil with higher DHA (HDTO) content was employed. It was the first to integrate microbiome and metabolome from a dose-effect perspective to investigate the influence of HDTO on gut dysbiosis and metabolic disorders in diet-induced obese mice. RESULTS: Higher DHA tuna oil was effective in reversing high-fat-diet-induced metabolic disorders and altering the composition and function of gut microbiota, but these effects were not uniformly dose dependent. The flora and metabolites that were targeted to be regulated by HDTO supplementation were Prevotella, Bifidobacterium, Olsenella, glycine, l-aspartate, l-serine, l-valine, l-isoleucine, l-threonine, l-tyrosine, glyceric acid, glycerol, butanedioic acid, and citrate, respectively. Functional pathway analysis revealed that alterations in these metabolic biomarkers were associated with six main metabolic pathways: glycine, serine, and threonine metabolism; glycerolipid metabolism; glyoxylate and dicarboxylate metabolism; alanine, aspartate, and glutamate metabolism; aminoacyl-tRNA biosynthesis, and the citrate cycle (TCA cycle). CONCLUSION: Various doses of HDTO could attenuate endogenous disorders to varying degrees by regulating multiple perturbed pathways to the normal state. This explicit dose research for novel fish oil with high-DHA will provide a valuable reference for those seeking to exploit its clinical therapeutic potential. © 2022 Society of Chemical Industry.

Novel high-docosahexaenoic-acid tuna oil supplementation modulates gut microbiota and alleviates obesity in high-fat diet mice.

Studies have documented the benefits of fish oil in different diseases because of its high n-3 polyunsaturated fatty acid content. However, these studies mostly used commercially available fish oil supplements with a ratio of 18/12 for eicosapentaenoic acid and docosahexaenoic acid (DHA). However, increasing DHA content for this commonly used ratio might bring out a varied metabolic effect, which have remained unclear. Thus, in this study, a novel tuna oil (TO) was applied to investigate the effect of high-DHA content on the alteration of the gut microbiota and obesity in high-fat diet mice. The results suggest that high-DHA TO (HDTO) supplementation notably ameliorates obesity and related lipid parameters and restores the expression of lipid metabolism-related genes. The benefits of TOs were derived from their modification of the gut microbiota composition and structure in mice. A high-fat diet triggered an increased Firmicutes/Bacteroidetes ratio that was remarkably restored by TOs. The number of obesity-promoting bacteria-Desulfovibrio, Paraeggerthella, Terrisporobacter, Millionella, Lachnoclostridium, Anaerobacterium, and Ruminiclostridium-was dramatically reduced. Desulfovibrio desulfuricans, Alistipes putredinis, and Millionella massiliensis, three dysbiosis-related species, were especially regulated by HDTO. Regarding the prevention of obesity, HDTO outperforms the normal TO. Intriguingly, HDTO feeding to HFD-fed mice might alter the arginine and proline metabolism of intestinal microbiota.