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Background:  A dietary supplement developed in Japan, OM-X ® , is the result of extended fermentation of dozens of edible vegetables, fruits, seaweeds, mushrooms, and includes 12 strains of Lactic acid bacteria (LAB) and Bifidobacterium . The supplements powerful antioxidant, anti-inflammatory properties, and regulatory effect on metabolizing liver enzymes have been reported. Senescence marker protein-30 (SMP30)/Gluconolactonase (GNL) Knockout (KO) mice, which lack the ability to biosynthesize Vitamin C (VC) in the body, were used in this study. The mice exhibited decreased antioxidant capacity in the blood, decreased liver function, and had poor hair growth due to the VC deficiency. The aim of the study was to examine the effects of oral administration of OM-X ® on VC deficiency from the viewpoint of comprehensive analysis of liver metabolism. Methods: SMP30/GNL KO and C57BL/6 (WT) mice were used in this study. The KO mice were divided into the following three groups: VC non-administration (VC minus), VC (0.15 W/V %) administration (VC plus), and no VC plus 0.6% OM-X ® administration (OM-X ® ) groups (n = 6 per group). Mice were kept under experimental conditions until they were euthanized at week 8 (age: 16 weeks old). Body weight and plasma biochemistry levels were measured.. Metabolomic analyses of harvested livers were performed. Results: In the VC minus group, a significant decrease in body weight and significant changes in plasma biochemistry parameters compared with the WT control or VC plus groups was observed. In the OM-X ® group, significant suppression or a suppressive trend was observed compared with the VC minus group. Liver metabolomic analysis showed that total adenylate levels decreased in the VC minus group, whereas OM-X ® administration significantly elevated total adenylate levels. In addition, the ratios of Glutathione (GSH)/ Glutathione disulfide (GSSG) and S-adenosylmethionine (SAM)/ S-adenosyl-L-homocysteine (SAH) and total glutathione levels were all significantly higher in the OM-X ® group than in the VC minus group. The glycerol 3-phosphate/ Dihydroxyacetone phosphate (DHAP) and putrescine/spermidine ratios were elevated in the VC minus group, whereas it was significantly lower in the OM-X ® group. Conclusion: The results showed that in SMP30/GNL KO mice, some organ damage may have occurred during VC deficiency, as indicated by weight loss, hepatic injury, and changes in triglyceride-related markers. OM-X ® had an effect on energy charge maintenance by elevating total adenylate levels, inducing antioxidant capacity via enhancing glutathione levels, and promoting protein synthesis, including polyamine synthesis. Altogether, the results revealed that OM-X ® prevents the adverse biological changes caused by VC deficiency in SMP30/GNL KO mice. Keywords: OM-X ® , SMP30/GNL KO mice, Vitamin C, metabolomic analysis.

Metabolomic analysis of SMP30/GNL knockout mice treated with fermented vegetable and fruit extract (OM-X®)