Methionine-restricted diets (MRD) have been shown to prevent high fat diet (HFD) induced complications including fat accumulation, insulin sensitivity decrease, oxidative stress and inflammation increase. We hypothesized that intestinal microbiota changes may mediate these effects, and this study aims to prove this hypothesis. Mice were fed a normal diet (ND, 0.86% methionine + 4% fat), a HF diet (HFD, 0.86% methionine + 20% fat), or a MRD (0.17% methionine + 20% fat) and euthanized at week 22. Our results showed that the HFD induced fat accumulation and gut microbiota dysbiosis; reduced short-chain fatty acid (SCFA) production; and increased intestinal permeability, inflammatory response, and oxidative stress. The MRD decreased the body weight, body fat rate, and blood glucose and plasma lipid levels; increased the abundance of putative SCFA-producing bacteria Bifidobacterium, Lactobacillus, Bacteroides, Roseburia, Coprococcus, and Ruminococcus and inflammation-inhibiting bacteria Oscillospira and Corynebacterium; and decreased the abundance of inflammation-producing bacteria Desulfovibrio in colonic contents. Moreover, the MRD improved intestinal barrier function, inflammatory response, and oxidative stress, and altered the metabolite levels of colonic contents (such as increasing SCFA and bile acid concentrations); the latter may have contributed to the prevention of HFD-induced obesity. In conclusion, the MRD can improve gut health by regulating the intestinal microbiota and its metabolite profiles in the HFD mice. Reducing methionine intake by simple dietary adjustment may be an effective method to improve intestinal health in animals and humans.

Dietary methionine restriction (MR) has been shown to delay aging and ameliorate age-related cognitive impairments. We hypothesized that changes in the gut microbiota may mediate these effects. To test this hypothesis, ICR mice subcutaneously injected with 150 mg kg⁻¹ day⁻¹ D-galactose were fed a normal (0.86% methionine) or an MR (0.17% methionine) diet for 2 months. Multiple behavioral experiments were performed, and the gut microbiota composition, metabolite profiles related to short-chain fatty acids (SCFAs) in the feces, and indicators related to the redox and inflammatory states in the hippocampus were further analyzed. Our results indicated that MR alleviated cognitive impairment (including non-spatial memory deficits, working memory deficits, and hippocampus-dependent spatial memory deficits) and anxiety-like behavior in D-Gal-induced aging mice. Furthermore, MR increased the abundance of putative SCFA-producing bacteria such as Lachnospiraceae, Turicibacter, Roseburia, Ruminococcaceae_UCG-014, Intestinimonas, Rikenellaceae, Tyzzerella, and H₂S-producing bacteria such as Desulfovibrio in feces. Moreover, MR reversed and normalized the levels of intestinal SCFAs (acetate, propionate, and butyrate) and important intermediate metabolites of the SCFAs (pyruvate, lactate, malate, fumarate, and succinate), abolished aging-induced oxidative stress and inflammatory responses, increased the levels of H₂S in the plasma and hippocampus, and selectively modulated the expression of multiple learning- and memory-related genes in the hippocampus. These findings suggest that MR improved the gut microbiota composition and SCFA production and alleviated oxidative stress and inflammatory responses in the hippocampus, which might prevent cognitive impairment in D-galactose-induced aging mice.

Dietary methionine restriction improves impairment of learning and memory function induced by obesity, likely by increasing H₂S production.

This study explored the effects of protein oxidation during milk processing on spatial learning and memory in rats. Increasing the heating time, fat content, and inlet air temperature during processing by boiling, microwave heating, spray-drying, or freeze-drying increases milk protein oxidation. Oxidative damage done to milk proteins by microwave heating is greater than that caused by boiling. Dityrosine (DT), as a kind of tyrosine oxidation product, is the most important marker of this process, especially during spray-drying. Rats received diets containing either SWM (spray-dried milk powder diet), FWM (freeze-dried milk powder diet), FWM + LDT (freeze-dried milk powder + low dityrosine diet, DT: 1.4 mg kg⁻¹), or FWM + HDT (freeze-dried milk powder + high dityrosine diet, DT: 2.8 mg kg⁻¹) for 6 weeks. We found that the SWM group, the FWM + LDT group, and the FWM + HDT group appeared to have various degrees of redox state imbalance and oxidative damage in plasma, liver, and brain tissues. Further, hippocampal inflammatory and apoptosis genes were significantly up-regulated in such groups, while learning and memory genes were significantly down-regulated. Eventually, varying degrees of spatial learning and memory impairment were demonstrated in those groups in the Morris water maze. This means that humans should control milk protein oxidation and improve the processing methods applied to food.

Dietary methionine restriction (MR) has many positive effects on metabolic health. Recent studies have indicated that overall insulin sensitivity is improved by dietary MR. This study aimed to determine the effects of MR on insulin signalling and glucose utilisation in the skeletal muscle of obese mice. First, male C57BL/6J mice in the CON group were fed a control diet (0.86% methionine + 4% fat) for 34 weeks, and others were fed a high-fat (HF) diet (0.86% methionine + 20% fat) for 10 weeks to induce obesity. Then, the mice were divided into four dietary groups: the HF group (maintained on the HF diet), HF + MR group (0.17% methionine + 20% fat), C* group (changed to a control diet, 0.86% methionine + 4% fat), and C* + MR group (0.17% methionine + 4% fat) for 24 weeks. Mice were euthanised at 8, 16 or 24 weeks. The results indicated that MR ameliorated obesity-induced hyperglycaemia and hyperinsulinemia. Moreover, MR up-regulated the gene expression of disulfide-bond A oxidoreductase-like protein and cystathionine-γ-lyase and promoted adiponectin and H₂S production in inguinal white adipose tissue. Furthermore, MR activated AMP-activated protein kinase and inhibited its downstream signalling and up-regulated insulin signalling-related molecules in gastrocnemius muscle. Overall, MR improved glucose metabolism via increasing glycogen synthesis, glycolysis, and aerobic oxidation. Interestingly, most parameters were equivalent between the HF + MR group and C* + MR group. These findings suggest that dietary MR can improve glucose metabolism in obese mice.