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.

Effects of the Sex Factor on Mouse Iodine Intake: Interactions between the Gut Microbiota Composition and Metabolic Syndromes.

Iodine plays a key role in maintaining thyroid homeostasis, which is influenced by hormones through almost all nucleated cells and is essential for growth and metabolism. The most common kinds of thyroid dysfunction, hypothyroidism and hyperthyroidism, are markedly related to iodine intake. In addition, the prevalence and incidence of hypothyroidism and hyperthyroidism are much higher in women than in men. However, the association between thyroid homeostasis and the gut microbiota is not yet completely clear, especially when comparing women and men. In this study, differences in the gut microbiota compositions, metabolic syndromes, and molecular mechanisms of female and male mice were investigated after iodine supplementation. The gut microbiota in male mice was changed more than that of female mice. The abundances of Muribacium intestinale, Barnesiella, Alloprevotella, Enterococcus, Desulfovibrionaceae, and Clostridium were significantly increased in female mice. This finding indicates that the high risk of thyroid disease in women could be related to the gut microbiota composition.

The gut microbiota mediates the protective effects of anserine supplementation on hyperuricaemia and associated renal inflammation.

Hyperuricaemia is a disease associated with elevated serum uric acid content, which has emerged rapidly in recent decades. The drugs used to treat clinical hyperuricaemia have side effects, and their safety is poor. However, anserine is a natural carnosine derivative that shows an anti-hyperuricaemic effect. A previous study demonstrated that anserine inhibits uric acid synthesis and promotes uric acid excretion, but there is no evidence regarding the effect of anserine from the perspective of the gut microbiota. In this study, the anti-hyperuricaemic and anti-inflammatory effects of anserine were explored in a diet-induced hyperuricaemic mouse model. Anserine alleviated hyperuricaemia and renal inflammation phenotypes, inhibited uric acid biosynthesis, promoted uric acid excretion, and inhibited NLRP3 inflammasome and TLR4/MyD88/NF-κB signalling pathway activation. The results showed that the anti-hyperuricaemic effect of anserine was dependent on the gut microbiota in the germ-free mice experiment. Furthermore, anserine treatment reversed gut microbiota dysbiosis, repaired the intestinal epithelial barrier and increased short-chain fatty acid production. Moreover, the anti-hyperuricaemic effect of anserine was transmissible by transplanting the faecal microbiota from anserine-treated mice, indicating that the protective effects were at least partially mediated by the gut microbiota. Thus, we identified a new and safe prebiotic material to alleviate hyperuricaemia and provided ideas for the development of oligopeptides.

Apostichopus japonicus Oligopeptide Induced Heterogeneity in the Gastrointestinal Tract Microbiota and Alleviated Hyperuricemia in a Microbiota-Dependent Manner.

SCOPE: This study aims to investigate the protective effect of Apostichopus japonicus oligopeptide (AJOP) on hyperuricemia, demonstrate the modulation of the gastrointestinal tract (GIT) microbiota, and clarify the underlying microbiota-dependent mechanism. METHODS AND RESULTS: Hyperuricemic mice treated with AJOP and subjected to corresponding fecal microbiota transplantation (FMT) are used to observe the beneficial effects of AJOP and microbiota. Gene transcriptions are measured using quantitative real-time PCR. The GIT (stomach, colon, cecum, and feces) microbiota is analyzed by 16S rDNA sequencing and the short-chain fatty acids are detected using GC-MS. Dietary administration of AJOP significantly alleviates hyperuricemia, regulates uric acid metabolism, inhibites the activation of the NLRP3 inflammasome and NF-κB-related signaling pathway, and restores m6A methylation levels. In addition, substantial heterogeneity is observed in GIT microbiota. Furthermore, FMT effectively alleviates hyperuricemia in mice by selectively regulating the corresponding pathways associated with AJOP treatment, indicating that the mechanism underlying the protective effects of AJOP is partly microbiota-dependent. CONCLUSION: This study demonstrates that AJOP exerts a protective effect on hyperuricemic mice by regulating uric acid metabolism, resulting in substantial heterogeneity among the GIT microbiota, thus mediating the beneficial effects in a microbiota-dependent manner.

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.

Protective effects of tuna meat oligopeptides (TMOP) supplementation on hyperuricemia and associated renal inflammation mediated by gut microbiota.

Recently, interest in using whole food-derived mixtures to alleviate chronic metabolic syndrome through potential synergistic interactions among different components is increasing. In this study, the effects and mechanisms of tuna meat oligopeptides (TMOP) on hyperuricemia and associated renal inflammation were investigated in mice. Dietary administration of TMOP alleviated hyperuricemia and renal inflammation phenotypes, reprogramed uric acid metabolism pathways, inhibited the activation of NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathways, and suppressed the phosphorylation of p65-NF-κB. In addition, TMOP treatments repaired the intestinal epithelial barrier, reversed the gut microbiota dysbiosis and increased the production of short-chain fatty acids. Moreover, the antihyperuricemia effects of TMOP were transmissible by transplanting the fecal microbiota from TMOP-treated mice, indicating that the protective effects were at least partially mediated by the gut microbiota. Thus, for the first time, we clarify the potential effects of TMOP as a whole food derived ingredient on alleviating hyperuricemia and renal inflammation in mice, and additional efforts are needed to confirm the beneficial effects of TMOP on humans.

Alterations of the Brain Proteome and Gut Microbiota in d-Galactose-Induced Brain-Aging Mice with Krill Oil Supplementation.

Brain aging is commonly associated with neurodegenerative disorders, but the ameliorative effect of krill oil and the underlying mechanism remain unclear. In this study, the components of krill oil were measured, and the antiaging effects of krill oil were investigated in mice with d-galactose (d-gal)-induced brain aging via proteomics and gut microbiota analysis. Krill oil treatment decreased the expression of truncated dopamine- and cAMP-regulated phosphoproteins and proteins involved in the calcium signaling pathway. In addition, the concentrations of dopamine were increased in the serum (p < 0.05) and brain (p > 0.05) due to the enhanced expressions of tyrosine-3-monooxygenase and aromatic l-amino acid decarboxylase. Moreover, krill oil alleviated gut microbiota dysbiosis, decreased the abundance of bacteria that consume the precursor tyrosine, and increased the abundance of Lactobacillus spp. and short-chain fatty acid producers. This study revealed the beneficial effect of krill oil against d-gal-induced brain aging and clarified the underlying mechanism through proteomics and gut microbiota analysis.