Acetyl tributyl citrate (ATBC) is a widely used phthalate substitute. Although ATBC is considered to be with a safe dosage of up to 1000 mg/kg/day, studies on its effects in some sensitive populations, such as diabetic patients, are relatively rare. Epidemiological studies have shown that there is a link between diabetes and nervous system diseases. However, toxicological studies have not fully confirmed this yet. In this study, glycolipid metabolism, cognitive deficits, brain tissue damage, levels of neurotransmitters, beta-amyloid plaques (Aβ), hyperphosphorylated tau protein (p-Tau), oxidative stress and inflammation, as well as glial cell homeostatic levels in the brain tissue of type 2 diabetes (T2DM) mice, were determined after ATBC exposure (0, 2, 20, and 200 mg/kg/day) for 90 days. The results confirmed that ATBC exposure aggravated the disorder of glycolipid metabolism and caused cognitive deficits in T2DM mice; induced histopathological alterations and Aβ and p-Tau accumulation, and reduced the levels of 5-hydroxytryptamine and acetylcholine in T2DM mouse brains; oxidative stress and glial cell homeostatic levels in T2DM mouse brains were also changed. Some of the adverse effects were gender-dependent. These findings support the theory that T2DM mice, especially males, are more sensitive to ATBC exposure. Although the safe dose of ATBC is high, prolonged exposure at seemingly safe concentrations has the potential to aggravate diabetes symptoms and cause brain tissue damage in T2DM mice.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) have the potential to alleviate alcoholic liver injury and play essential roles in treating alcohol-exposed liver disease; however, the hepatoprotective effects and mechanisms remain elusive. In this study, we investigated the hepatoprotective effects of HDPs and their potential mechanisms in alcohol-exposed mice through liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels, and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. When applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria, significant increases in Firmicutes at the phylum level, increased Lactobacillus abundance, and decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid and glycerophospholipid metabolism, and identified two important metabolites—C00157 (phosphatidylcholine, a glycerophospholipid plays a central role in energy production) and C04230 (1-Acyl-sn-glycero-3-phosphocholine, a lysophospholipid involved in the breakdown of phospholipids)—involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs have a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

Flavor-relevant trace volatiles and microbial communities were examined in six sauce-aroma high-temperature Daqu samples. Headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME-GC-MS) quantified 210 trace volatile compounds across 14 chemical classes. Orthogonal partial least squares discriminant analysis (OPLS-DA) with variable importance in projection (VIP) screening was integrated with sensory scoring, correlation analysis, and molecular docking to an olfactory receptor model. Volatile profiles showed clear stratification in total abundance. Pyrazines dominated the high-total group. Tetramethylpyrazine served as a major driver. Sensory evaluation indicated that aroma explained overall quality best. (E)-2-pentenal and dimethyl trisulfide showed significant positive associations with aroma and overall scores. In the olfactory receptor, the polar residue module that provides directional constraints for Daqu odor activation was formed by Ser75, Ser92, Ser152, Ser258, Thr74, Thr76, Thr98, Thr200, Gln99, and Glu94. The hydrogen-bond or charge network was further reinforced by Arg150, Arg262, Asn194, His180, His261, Asp182, and Gln181. The core discriminant set comprised acetic acid, hexanoic acid, (E)-2-pentenal, nonanal, decanal, dimethyl trisulfide, trans-3-methyl-2-n-propylthiophane, 2-hexanone oxime, ethyl linoleate, propylene glycol, 2-ethenyl-6-methylpyrazine, 4-methylquinazoline, 5-methyl-2-phenyl-2-hexenal, and 1,2,3,4-tetramethoxybenzene. Sequencing revealed higher bacterial diversity than fungal. Bacillus and Kroppenstedtia were dominant bacterial genera. Aspergillus, Paecilomyces, Monascus, and Penicillium were major fungal genera. Correlation patterns suggested that Bacillus and Monascus were positively linked to acetic acid and 1,2,3,4-tetramethoxybenzene. Together, these results connected chemical fingerprints, sensory performance, receptor-level plausibility, and microbial ecology. Concrete targets are provided for quality control of high-temperature Daqu.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) has the potential to alleviate alcoholic liver injury may play essential roles in treating for alcohol-exposed liver disease, however, the hepatoprotective effects and mechanisms remain unclear. In this study, the hepatoprotective effects of HDPs and its potential mechanisms were investigated in alcohol-exposed mice by liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. By applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria while significant increases in Firmicutes at the phylum level, and increased Lactobacillus abundance while decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid metabolism and glycerophospholipid metabolism and identified two important metabolites C00157 and C04230 involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs has a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.