Curcumin alleviates traumatic brain injury induced by gas explosion through modulating gut microbiota and suppressing the LPS/TLR4/MyD88/NF-κB pathway.

Gas explosions (GE) are a prevalent and widespread cause of traumatic brain injury (TBI) in coal miners. However, the impact and mechanism of curcumin on GE-induced TBI in rats remain unclear. In this study, we simulated GE-induced TBI in rats and administered curcumin orally at a dose of 100 mg/kg every other day for 7 days to modulate the gut microbiota in TBI rats. We employed 16S rRNA sequencing and LC-MS/MS metabolomic analysis to investigate changes in the intestinal flora and its metabolic profile. Additionally, we utilized ELISA, protein assays, and immunohistochemistry to assess neuroinflammatory signaling molecules for validation. In a rat TBI model, GE resulted in weight loss, pathological abnormalities, and cortical hemorrhage. Treatment with curcumin significantly mitigated histological abnormalities and microscopic mitochondrial structural changes in brain tissue. Furthermore, curcumin treatment markedly ameliorated GE-induced brain dysfunction by reducing the levels of several neuroinflammatory signaling molecules, including neuron-specific enolase, interleukin (IL)-1ß, IL-6, and cryptothermic protein 3. Notably, curcumin reshaped the gut microbiome by enhancing evenness, richness, and composition. Prevotella_9, Alloprevotella, Bacilli, Lactobacillales, Proteobacteria, and Gammaproteobacteria were identified as prominent members of the gut microbiota, increasing the linear discriminant analysis scores and specifically enhancing the abundance of bacteria involved in the nuclear factor (NF)-κB signaling pathway, such as Lachnospiraceae and Roseburia. Additionally, there were substantial alterations in serum metabolites associated with metabolic NF-κB signaling pathways in the model group. Curcumin administration reduced serum lipopolysaccharide levels and downregulated downstream Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/NF-κB signaling. Furthermore, curcumin alleviated GE-induced TBI in rats by modulating the gut microbiota and its metabolites. Based on these protective effects, curcumin may exert its influence on the gut microbiota and the TLR4/MyD88/NF-κB signaling pathways to ameliorate GE-induced TBI.

Alterations in the gut microbiota and its metabolic profile of PM2.5 exposure-induced thyroid dysfunction rats.

Fine particulate matter (PM2.5) has drawn more and more interest due to its adverse effects on health. Thyroid has been demonstrated to be the key organ impacted by PM2.5. However, the mechanisms for PM2.5 exposure-induced thyrotoxicity remain unclear. To explore the mechanisms, a rat thyroid injury model was established by exposing rats to PM2.5 via passive pulmonary inhalation. Thyroid hormones and thyroid function proteins were detected. The thyroid function affected by PM2.5 exposure was investigated via metabolomics analysis using liquid chromatography-mass spectrometry and 16S rRNA gene sequencing. Results showed that PM2.5 exposure induced remarkable alterations in gut microbiome evenness, richness, and composition. Metabolomics profiling revealed that the urine metabolites levels were changed by PM2.5 exposure. The altered gut microbiota and urine metabolites showed significant correlations with thyroid function indicators (total T3, total T4 and thyrotropin hormone, etc.). These metabolites were involved in metabolic pathways including thyroid hormone synthesis, metabolisms of tryptophan, d-Glutamine and D-glutamate, histidine, glutathione, etc. The altered gut microbiota showed significant correlations with urine metabolites (glutathione, citric acid, D-Glutamic acid, kynurenic acid and 5-Aminopentanoic acid, etc.). For example, the taurocholic acid levels positively correlated with the relative abundance of several genera including Elusimicrobium (r = 0.9741, p = 0.000000), Muribaculum (r = 0.9886, p = 0.000000), Candidatus_Obscuribacter (r = 0.8423, p = 0.000585), Eubacterium (r = 0.9237, p = 0.000017), and Parabacteroides (r = 0.8813, p = 0.000150), while it negatively correlated with the relative abundance of Prevotella (r = -0.8070, p = 0.001509). PM2.5 exposure-induced thyrotoxicity led to remarkable alterations both in gut microbiome composition and some metabolites involved in metabolic pathways. The altered intestinal flora and metabolites can in turn influence thyroid function in rats. These findings may provide novel insights regarding perturbations of the gut-thyroid axis as a new mechanism for PM2.5 exposure-induced thyrotoxicity.

Protective effects of curcumin against thyroid hormone imbalance after gas explosion-induced traumatic brain injury via activation of the hypothalamic-pituitary-thyroid axis in male rats.

Gas explosion (GE)-induced traumatic brain injury (TBI) can affect thyroid hormone (TH) homeostasis in miners. This study evaluated the effects of hepatic transthyretin and hypothalamic-pituitary-thyroid (HPT) axis on thyroids and explored the protective effect and mechanism of curcumin on GE-induced TBI. Thirty rats were randomly divided into three groups (10 per group): first group (control group)-rats received GE treatment once; second group (GE group)-rats received GE treatment (200 m from the source of the explosion once); third group (GE + Cur group)-rats received curcumin (Cur) by lavage at a dose of 100 mg/kg/day once every other day for 7 days after receiving GE. After GE, the pathological changes were analyzed by hemotoxylin and eosin staining, and the levels of serum reactive oxygen species (ROS), urine iodine (UI), THs, nuclear factor-kappa B (NF-κB), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and malondialdehyde (MDA) were analyzed using ELISA. Expression of proteins in the HPT axis of rats was examined by immunohistochemistry and Western blotting. We found that GE could induce pathologic changes in rat thyroid and liver. Serum levels of THs, NF-κB and serum redox state became unbalanced in rats after GE. GE could inhibit the biosynthesis and biotransformation of THs by affecting key HPT axis proteins. Additionally, GE reduced the level of hepatic transthyretin. Serum THs levels and thyroid sections were almost recovered to normal after curcumin treatment. The aforementioned key HPT axis proteins in the curcumin group showed opposite expression trends. In summary, GE affected THs balance while curcumin can protect against these injury effects by affecting TH biosynthesis, biotransformation, and transport, and inducing oxidative stress and inflammatory responses.