Background: Environmental noise exposure is linked to neuroinflammation and imbalance of the gut microbiota. Promoting gut microbiota homeostasis may be a key factor in relieving the deleterious non-auditory effects of noise. This study aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) intervention on noise-induced cognitive deficits and systemic inflammation in rats.Methods: Learning and memory were assessed using the Morris water maze, while 16S rRNA sequencing and gas chromatography-mass spectrometry were used to analyze the gut microbiota and short-chain fatty acid (SCFA) content. Endothelial tight junction proteins and serum inflammatory mediators were assessed to explore the underlying pathological mechanisms.Results: The results indicated that Lactobacillus rhamnosus GG intervention ameliorated noise-induced memory deterioration, promoted the proliferation of beneficial bacteria, inhibited the growth of harmful bacteria, improved dysregulation of SCFA-producing bacteria, and regulated SCFA levels. Mechanistically, noise exposure led to a decrease in tight junction proteins in the gut and hippocampus and an increase in serum inflammatory mediators, which were significantly alleviated by Lactobacillus rhamnosus GG intervention.Conclusion: Taken together, Lactobacillus rhamnosus GG intervention reduced gut bacterial translocation, restored gut and blood-brain barrier functions, and improved gut bacterial balance in rats exposed to chronic noise, thereby protecting against cognitive deficits and systemic inflammation by modulating the gut-brain axis.

Inorganic arsenic is a well-known environmental toxicant and carcinogen, and there is overwhelming evidence for an association between this metalloid poisoning and hepatic diseases. However, the biological mechanism involved is not well characterized. In the present study, we probed how inorganic arsenic modulates the hepatic polarization of macrophages, as well as roles of PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy participates in regulating the metalloid-mediated macrophage polarization. Our results indicate that acute arsenic exposure induced macrophage polarization with up-regulated gene expression of inducible nitric oxide synthase (Inos) and arginase-1 (Arg1), monocyte chemotactic protein-1 (Mcp-1) and macrophage inflammatory protein-2 (Mip-2), tumor necrosis factor (Tnf)-α, interleukin (Il)-1β and Il-6, as well as anti-inflammatory factors Il-4 and Il-10. In parallel, we demonstrated the disrupted hepatic redox balance typically characterized by the up-regulation of hydrogen peroxide (H₂O₂) and glutathione (GSH), and activation of PINK1/Parkin-mediated mitophagy in the livers of acute arsenic-exposed mice. In addition, our results demonstrate that it might be the PINK1/Parkin-mediated mitophagy that renders hepatic macrophage refractory to arsenic-induced up-regulation of the genes Inos, Mcp-1, Mip-2, Tnf-α, Il-1β, Il-6 and Il-4. In this regard, this is the first time the protective effects of PINK1/Parkin-mediated mitophagy in inorganic arsenic-induced hepatic macrophage polarization in vivo have been reported. These findings add novel insights into the arsenical immunotoxicity and provide a basis for the preve.ntive and therapeutic potential of PINK1/Parkin-mediated mitophagy in arsenic poisoning.

Both fine particulate matter (PM_2.5) and high-fat diet (HFD) can cause changes in glucose and lipid metabolisms; however, the mechanism of their combined effects on glucose and lipid metabolisms is still unclear. This study aimed to investigate the effects of PM_2.5 and HFD co-exposure on glucose and lipid metabolisms and mitochondrial DNA methylation in Wistar rats. PM_2.5 and HFD co-treatment led to an increase in fasting blood glucose levels, an alteration in glucose tolerance, and a decrease in high density lipoprotein cholesterol (HDL-C) levels in Wistar rats. In the homeostasis model assessment (HOMA), HOMA-insulin resistance (HOMA-IR) increased and HOMA-insulin sensitivity (HOMA-IS) and HOMA-β cell function (HOMA-β) decreased in rats co-exposed to PM_2.5 and HFD. Additionally, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were increased, and interleukin-6 (IL-6) and interleukin-10 (IL-10) mRNA expressions were upregulated in the brown adipose tissue following PM_2.5 and HFD co-exposure. Bisulfite pyrosequencing was used to detect the methylation levels of mitochondrially-encoded genes (MT-COX1, MT-COX2 and MT-COX3), and MT-COX3 was hypermethylated in the PM_2.5 and HFD co-exposure group. Moreover, MT-COX3-Pos.2 mediated 36.41 % (95 % CI: -27.42, -0.75) of the total effect of PM_2.5 and HFD exposure on HOMA-β. Our study suggests that PM_2.5 and HFD co-exposure led to changes in glucose and lipid metabolisms in rats, which may be related to oxidative stress and inflammatory responses, followed by mitochondrial stress leading to MT-COX3 hypermethylation. Moreover, MT-COX3-Pos.2 was found for the first time as a mediator in the impact of co-exposure to PM_2.5 and HFD on β-cell function. It could serve as a potential biomarker, offering fresh insights into the prevention and treatment of metabolic diseases.

Fine particulate matter (PM_2.5) and high-fat diet (HFD) are known to contribute to blood glucose metabolic disorders. However, limited research has investigated the combined impact of PM_2.5 and HFD on blood glucose metabolism. This study aimed to explore the joint effects of PM_2.5 and HFD on blood glucose metabolism in rats using serum metabolomics and to identify involved metabolites and metabolic pathways. The 32 male Wistar rats were exposed to filtered air (FA) or PM_2.5 (real-world inhaled, concentrated PM_2.5, 8 times the ambient level, ranging from 131.42 to 773.44 μg/m³) and fed normal diet (ND) or HFD for 8 weeks. The rats were divided into four groups (n = 8/group): ND-FA, ND-PM_2.5, HFD-FA and HFD-PM_2.5 groups. Blood samples were collected to determine fasting glucose (FBG), plasma insulin and glucose tolerance test and HOMA Insulin Resistance (HOMA-IR) index was calculated. Finally, the serum metabolism of rats was analyzed by ultra-high performance liquid chromatography/mass spectrometry (UHPLC-MS). Then we constructed the partial least squares discriminant analysis (PLS-DA) model to screen the differential metabolites, and performed pathway analysis to screen the main metabolic pathways. Results showed that combined effect of PM_2.5 and HFD caused changes in glucose tolerance, increased FBG levels and HOMA-IR in rats and there were interactions between PM_2.5 and HFD in FBG and insulin. By metabonomic analysis, the serum differential metabolites pregnenolone and progesterone, which involved in steroid hormone biosynthesis, were two different metabolites in the ND groups. In the HFD groups, the serum differential metabolites were L-tyrosine and phosphorylcholine, which involved in glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. When PM_2.5 and HFD coexist, they may lead to more severe and complex effects on glucose metabolism by affecting lipid metabolism and amino acid metabolism. Therefore, reducing PM_2.5 exposure and controlling dietary structure are important measures for preventing and reducing glucose metabolism disorders.