Acute sleep deprivation (ASD) is often observed in shift workers and characterized by drowsiness and unrelenting exhaustion. The physiological and psychological effects of ASD include anxiety, depression, cognitive impairment, systemic inflammation, stress responses, and disruptions of gut microbiota. However, the mechanisms involved in the ASD-associated circadian dysregulations with regard to gut dysbiosis, systemic inflammation, physiological modulation, and psychiatry disorders remain unclear. The aim of this study was to investigate whether central nervous system disorders induced by ASD are related to inflammation, barrier dysfunction, and circadian dysregulation. We also assessed impacts on microbiota succession. Male C57BL/6 mice were randomly allocated to the control and sleep deprivation (SD) groups. Mice in the SD group were subjected to 72 h of paradoxical SD using the modified multiple-platform method for ASD induction (72 h rapid eye movement-SD). The effects of ASD on dietary consumption, behaviors, cytokines, microbiota, and functional genes were determined. The appetite of the SD group was significantly higher than that of the control group, but the body weight was significantly lower than that of the control group. The anxiety-like behaviors were found in the SD group. Alpha and beta diversity of microbiota showed significant decrease after ASD induction; the relative abundance of Candidatus_Arthromitus and Enterobacter was increased, whereas that abundance of Lactobacillus, Muribaculum, Monoglobus, Parasutterella, and others was decreased in the SD group. These effects were accompanied by reduction in fecal propionic acid. In the proximal colon, the SD group exhibited significantly higher inflammation (tumor necrosis factor-α [TNF-α]) and dysregulation of the circadian rhythms (brain and muscle ARNT-like 1 [BMAL1] and cryptochrome circadian regulator 1 [CRY1]) and tight junction genes (occludin [OCLN]) than the control group. Gut barrier dysfunction slightly increased the plasma concentration of lipopolysaccharide and significantly elevated TNF-α. Inflammatory signals might be transduced through the brain via TNF receptor superfamily member 1 A (TNFRSF1A), which significantly increased the levels of microglia activation marker (ionized calcium-binding adapter molecule 1 [IBA1]) and chemokine (intercellular adhesion molecule 1 [ICAM1]) in the cerebral cortex. The serotonin receptor (5-hydroxytryptamine 1A receptor [5-HT_1AR]) was significantly downregulated in the hippocampus. In summary, 72 h of rapid eye movement-SD induced physiological and psychological stress, which led to disruption of the circadian rhythms and gut microbiota dysbiosis; these effects were related to decrement of short chain fatty acids, gut inflammation, and hyperpermeability. The microbiota may be utilized as preventive and therapeutic strategies for ASD from the perspectives of medicine and nutrition.

Dietary pattern and food choice are associated with expansion of gut pathobionts and risk for metabolic and colonic disease. However, the effects of dietary interventions on intestinal microbiota remain unclear.

(1) Background: Recently, a growing number of studies have provided evidence to suggest a strong correlation between air pollution exposure and attention-deficit/hyperactivity disorder (ADHD). In this study, we assessed the relationship between early-life exposure to particulate matter (PM)₁₀, PM₂.₅, and ADHD; (2) Methods: The National Health Insurance Research Database (NHIRD) contains the medical records, drug information, inspection data, etc., of the people of Taiwan, and, thus, could serve as an important research resource. Air pollution data were based on daily data from the Environmental Protection Administration Executive Yuan, R.O.C. (Taiwan). These included particulate matter (PM_2.5 and PM₁₀). The two databases were merged according to the living area of the insured and the location of the air quality monitoring station; (3) Results: The highest levels of air pollutants, including PM_2.5 (adjusted hazard ratio (aHR) = 1.79; 95% confidence interval (CI) = 1.58–2.02) and PM₁₀ (aHR = 1.53; 95% CI = 1.37–1.70), had a significantly higher risk of ADHD; (4) Conclusions: As such, measures for air quality control that meet the WHO air quality guidelines should be strictly and uniformly implemented by Taiwanese government authorities.

Recent studies have shown that high dietary fructose intake enhances intestinal tumor growth in mice. Our previous work indicated that glucose enables hypoxic colorectal cancer (CRC) cells to resist receptor-interacting protein (RIP)-dependent necroptosis. Despite having the same chemical formula, glucose and fructose are absorbed through different transporters yet both can enter the glycolytic metabolic pathway. The excessive intake of dietary fructose, leading to its overflow into the colon, allows colonic cells to absorb fructose apically. This study explores the mechanisms behind apical fructose-mediated death resistance in CRC cells under hypoxic stress. Utilizing three CRC cell lines (Caco-2, HT29, and T84) under normoxic and hypoxic conditions with varying fructose concentrations, we assessed lactate dehydrogenase (LDH) activity, RIP1/3 complex formation (a necroptosis marker), and cell integrity. We investigated the role of fructose in glycolytic-mediated death resistance using glycolytic inhibitors iodoacetate (IA, a glycolytic inhibitor to glyceraldehyde 3-phosphate dehydrogenase), and UK5099 (UK, an inhibitor to mitochondrial pyruvate carrier). Our findings reveal that apical fructose prevents the hypoxia-induced RIP-dependent necroptosis in Caco-2 and HT29 cells. Fructose exposure under hypoxia also preserved epithelial integrity. IA, but not UK, blocked fructose-mediated glycolytic metabolite production and necrosis, indicating that anaerobic glycolytic metabolites facilitate death resistance. Notably, fructose treatment upregulated pyruvate kinase (PK)-M1 mRNA in hypoxic Caco-2 and HT29 cells, while PKM2 upregulation was exclusive to HT29 cells. In conclusion, apical fructose utilization through glycolysis effectively inhibits hypoxia-induced RIP-dependent necroptosis in CRC cells, shedding light on potential metabolic adaptation mechanisms in the tumor microenvironment and suggesting novel targets for therapeutic intervention.

Malignant cells often exhibit significant metabolic alterations, including the utilization of different nutrients to meet energetic and biosynthetic demands. Recent studies have shown that glutamine can support primary colorectal tumor growth and also serve as an alternate energy source during distant metastasis under glucose-limited conditions. However, the overall effects of glutamine on cancer cell physiology are not completely understood. In this study, we investigated how glutamine impacts epithelial integrity in colorectal cancer cells under glucose deprivation. Human colorectal cancer (Caco-2) cells were grown to confluency in transwells and cultured in glucose/pyruvate-free DMEM with various glutamine concentrations (0–50 mM). Cell viability was assessed, and monolayer integrity was examined in terms of transepithelial resistance (TER) and paracellular permeability. Tight junction (TJ) component proteins were examined by immunofluorescence staining and Western blotting. A dose-dependent decrease in TER was observed in Caco-2 cells, but paracellular permeability was not affected after 24 h incubation with glutamine. At the same time, the TJ proteins, zonula occludens (ZO)-1 and Claudin-1, showed lateral undulations and punctate staining patterns accompanied by enlargement of cellular and nuclear sizes. Furthermore, decreased protein levels of ZO-1, but not claudin-1, were found in detergent-insoluble cellular fractions. Notably, the decreased TER and alterations in TJ structure were not associated with cell viability changes. Moreover, the addition of glutamate, which is produced by the first step of glutamine catabolism, had no impact on TER. Our results suggested that the enteral glutamine may play an important role in the regulation of TJ dynamics in colorectal cancer cells.

Superior mesenteric ischemia/reperfusion (I/R) causes barrier dysfunction and facilitates bacterial translocation (BT) in the small intestine, which can even lead to systemic sepsis. Our previous research showed that luminal administration of glucose and its anaerobic glycolytic metabolites exerted cytoprotective effects on epithelial cells and ameliorated I/R-induced BT in the liver and spleen. Notably, the reduction of BT occurs over the whole intestinal tract, not only restricted in the ligated glucose-containing loop. In this study, we hypothesized that local jejunal glucose-contacting might confer on the remote intestinal epithelium regeneration potential, fortify their barrier function and goblet cell secretory activity. Two 10-cm jejunal segments were isolated in Wistar rats. One segment was ligatured at both ends and infused with Krebs buffer containing 0- or 50-mM glucose (local loop), whereas the adjacent segment was left unaltered and not exposed to glucose (remote loop). The rats then underwent either a sham operation or I/R challenge by occlusion of the superior mesenteric artery for 20 min, followed by reperfusion for 1 h. Enteral addition of glucose in the local jejunum loop alleviated ischemia-induced barrier defects, histopathological scores, cell death, and mucosal inflammation (myeloperoxidase and inflammatory cytokine production) in the remote jejunum. After ischemia, goblet cells in the remote jejunum showed cavitation of mucin granules and low MUC2 expression. Local addition of glucose enhanced MUC2 synthesis and stimulated a jet-like mucus secretion in the remote jejunum, which was accompanied by the restoration of crypt activity. Our results showed local enteral glucose effectively mitigates I/R-induced barrier dysfunction, suggesting that local glucose-stimulated mucus secretion by remote goblet cells may serve to mitigate mucosal inflammation and BT. We provide a more precise barrier protection role of enteral glucose upon I/R challenge, presenting new opportunities for future therapeutic potential.