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Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that occurs in children characterized by inattention and hyperactivity. Prenatal alcohol exposure (PAE) can disrupt fetal neuronal development and cause an ADHD-like hyperactive behavior in the offspring. In this study, we hypothesized that metabolic disturbance would involve in ADHD neuropathology and aimed to investigate the changes in metabolite profile in PAE-induced ADHD-like model and the effects of HX106, a nutraceutical, on ADHD-like pathophysiology and metabolite changes. To this end, we administered HX106 to the mouse offspring affected by PAE (OPAE) and assessed the hyperactivity using the open field test. We observed that HX106-treated OPAE showed less hyperactive behavior than vehicle-treated OPAE. The effects of HX106 were found to be related to the regulation of dopamine transporter and D2 dopamine receptor expression. Furthermore, using gas chromatography time-of-flight mass spectrometry-based metabolomics, we explored the metabolite changes among the experimental groups. The metabolite profile, particularly related with the amino acids, linoleic acid and amino sugar pathways, was altered by PAE and reversed by HX106 treatment partially similar to that observed in the control group. Overall, this study suggest that metabolite alteration would be involved in ADHD pathology and that HX106 can be an efficient supplement to overcome ADHD by regulating dopamine signaling-related protein expression and metabolite changes.

Caffeine intake is strongly linked to lipid metabolism. We previously reported the age-dependent physiological effects of caffeine intake in a Caenorhabditis elegans model. Since nutritional status can actively influence metabolism and overall health, in this study, we evaluated the effect of caffeine intake on lipid metabolism in adult-stage C. elegans. We found that, in C. elegans, fat storage and the level of phosphoethanolamine (PE) were significantly reduced with caffeine intake. In addition, mitochondrial activity decreased and mitochondrial morphology was disrupted, and the expression of oxidative stress response genes, hsp-6, gst-4, and daf-16, was induced by caffeine intake. Furthermore, the level of an energy metabolism sensor, phospho-AMP-activated protein kinase, was increased, whereas the expression of the sterol regulatory element binding protein gene and its target stearoyl-CoA desaturase genes, fat-5, -6, and -7, was decreased with caffeine intake. These findings suggest that caffeine intake causes mitochondrial dysfunction and reduces lipogenesis. Interestingly, these changes induced by caffeine intake were partially alleviated by PE supplementation, suggesting that the reduction in mitochondrial activity and lipogenesis is in part because of the low PE level, and proper dietary supplementation can improve organelle integrity.

Phytonutrients and vitamin and mineral supplementation have been reported to provide increased antioxidant capacity in humans; however, there is still controversy. In the current clinical trial, we examined the antioxidant and DNA protection capacity of a plant-based, multi-vitamin/mineral, and phytonutrient (PMP) supplementation in healthy adults who were habitually low in the consumption of fruits and vegetables. This study was an eight-week, double-blind, randomized, parallel-arm, and placebo-controlled trial. PMP supplementation for eight weeks reduced reactive oxygen species (ROS) and prevented DNA damage without altering endogenous antioxidant system. Plasma vitamins and phytonutrients were significantly correlated with ROS scavenging and DNA damage. In addition, gene expression analysis in PBMC showed subtle changes in superoxide metabolic processes. In this study, we showed that supplementation with a PMP significantly improved ROS scavenging activity and prevented DNA damage. However, additional research is still needed to further identify mechanisms of actions and the role of circulating phytonutrient metabolites.

We aimed to identify metabolites involved in the anti-obesity effects of Platycodon grandiflorum (PG) in high-fat diet (HFD)-fed mice using mass spectrometry (MS)-based metabolomic techniques. C57BL/6J mice were divided into four groups: normal diet (ND)-fed mice, HFD-fed mice, HFD with 1% PG extract-fed mice (HPGL), and HFD with 5% PG extract-fed mice (HPGH). After 8 weeks, the HFD group gained more weight than the ND group, while dietary 5% PG extract attenuated this change. The partial least squares discriminant analysis (PLS-DA) score plots showed a clear distinction between experimental groups in serum and liver markers. We also identified 10 and 32 metabolites in the serum and liver, respectively, as potential biomarkers that could explain the effect of high-dose PG added to HFD-fed mice, which were strongly involved in amino acid metabolism (glycine, serine, threonine, methionine, glutamate, phenylalanine, ornithine, lysine, and tyrosine), TCA cycle (fumarate and succinate), lipid metabolism (linoleic and oleic acid methyl esters, oleamide, and cholesterol), purine/pyrimidine metabolism (uracil and hypoxanthine), carbohydrate metabolism (maltose), and glycerophospholipid metabolism (phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylcholines, and lysophosphatidylethanolamines). We suggest that further studies on these metabolites could help us gain a better understanding of both HFD-induced obesity and the effects of PG.

Probiotic fermentation of plant-based materials can lead to the generation of various bioactive substances via bacterial metabolites and the biotransformation of phenolic compounds. We compared the metabolic differences between fermentation by Limosilactobacillus fermentum KCTC15072BP (LFG) and fermentation by Lactiplantibacillus plantarum KGMB00831 (LPG) in guava leaf extract (0%, 0.5%, and 2% (w/v))-supplemented medium via non-targeted metabolite profiling. By performing multivariate statistical analysis and comparing the different guava leaf extract groups, 21 guava-derived and 30 bacterial metabolites were identified. The contents of guava-derived glucogallin, gallic acid, and sugar alcohols were significantly higher in LFG than they were in LPG. Similarly, significantly higher contents of guava-derived pyrogallol, vanillic acid, naringenin, phloretin, and aromatic amino acid catabolites were obtained with LPG than with LFG. LFG led to significantly higher antioxidant activities than LPG, while LPG led to significantly higher antiglycation activity than LFG. Interestingly, the fermentation-induced increase in the guava-leaf-extract-supplemented group was significantly higher than that in the control group. Thus, the increased bioactivity induced by guava fermentation with the Lactobacillaceae strain may be influenced by the synergistic effects between microbial metabolites and plant-derived compounds. Overall, examining the metabolic changes in plant-based food fermentation by differentiating the origin of metabolites provides a better understanding of food fermentation.