RESUMEN
Exercise enhances synaptic plasticity and alleviates depression symptoms, but the mechanism through which exercise improves high-fat diet-induced depression remains unclear. In this study, 6-week-old male C57BL/6J mice were administered a high-fat diet (HFD, 60% kcal from fat) to a HFD model for 8 weeks. The RUN group also received 1 h of daily treadmill exercise in combination with the HFD. Depressive-like behaviors were evaluated by behavioral assessments for all groups. The key mediator of the effect of exercise on high-fat diet-induced depressive-like behaviors was detected by RNA-seq. The morphology and function of the neurons were evaluated via Nissl staining, Golgi staining, electron microscopy and electrophysiological experiments. The results showed that exercise attenuated high-fat diet-induced depressive-like behavior and reversed hippocampal gene expression changes. RNA-seq revealed Wnt5a, which was a key mediator of the effect of exercise on high-fat diet-induced depressive-like behaviors. Further work revealed that exercise significantly activated neuronal autophagy in the hippocampal CA1 region via the Wnt5a/CamkII signaling pathway, which enhanced synaptic plasticity to alleviate HFD-induced depressive-like behavior. However, the Wnt5a inhibitor Box5 suppressed the ameliorative effects of exercise. Therefore, this work highlights the critical role of Wnt5a, which is necessary for exercise to improve high-fat diet-induced depression.
Asunto(s)
Autofagia , Depresión , Dieta Alta en Grasa , Hipocampo , Ratones Endogámicos C57BL , Plasticidad Neuronal , Neuronas , Condicionamiento Físico Animal , Animales , Dieta Alta en Grasa/efectos adversos , Masculino , Hipocampo/metabolismo , Hipocampo/patología , Ratones , Neuronas/metabolismo , Conducta Animal , Transducción de SeñalRESUMEN
The communication mechanism of the gut-lung axis has received increasing attention in recent years, particularly in acute respiratory infectious diseases such as influenza. The peripheral immune system serves as a crucial bridge between the gut and the lungs, two organs that are not in close proximity to each other. However, the specific communication mechanism involving gut microbiota, immune cells, and their anti-influenza effects in the lung remains to be further elucidated. In this study, the effects of 731 species of peripheral immune cells and 211 different gut microbiota on influenza outcomes were analyzed using a two-sample Mendelian randomization analysis. After identifying specific species of gut microbiota and peripheral immune cells associated with influenza outcomes, mediation analyses were conducted to determine the mediating effects of specific immune cells in the protective or injurious effects of influenza mediated by gut microbiota. 19 species of gut microbiota and 75 types of peripheral immune cells were identified as being associated with influenza susceptibility. After rigorous screening, 12 combinations were analyzed for mediated effects. Notably, the down-regulation of CD64 on CD14- CD16- cells mediated 21.10% and 18.55% of the protective effect of Alcaligenaceae and Dorea against influenza, respectively. In conclusion, focusing on influenza, this study genetically inferred different types of gut microbiota and peripheral immune cells to determine their protective or risk factors. Furthermore, mediation analysis was used to determine the proportion of mediating effects of peripheral immune cells in gut microbiota-mediated susceptibility to influenza. This helps elucidate the gut-lung axis mechanism by which gut microbiota affects influenza susceptibility from the perspective of regulation of peripheral immune cells.
Asunto(s)
Microbioma Gastrointestinal , Gripe Humana , Microbioma Gastrointestinal/inmunología , Humanos , Gripe Humana/inmunología , Predisposición Genética a la Enfermedad , Susceptibilidad a Enfermedades , Análisis de la Aleatorización Mendeliana , Pulmón/inmunología , Pulmón/microbiologíaRESUMEN
BACKGROUND: Dietary intervention is the preferred approach for the prevention and clinical management of gout. Nevertheless, the existing evidence regarding the influence of specific foods on gout is insufficient. METHODS: We used two-sample Mendelian randomization for genetic prediction to analyze the relationship between the intake of more than a dozen daily food items, such as pork, beef, cheese, and poultry, and dietary macronutrient intake (fat, protein, carbohydrates, and sugar) and the risk of developing gout and elevating the serum uric acid level. Inverse-variance weighted MR analyses were used as the main evaluation method, and the reliability of the results was tested by a sensitivity analysis. RESULTS: Cheese intake was associated with lower serum uric acid levels, and tea intake (OR = 0.523, [95%CI: 0.348~0.784], p = 0.002), coffee intake (OR = 0.449, [95%CI: 0.229~0.882], p = 0.020), and dried fruit intake (OR = 0.533, [95%CI: 0.286~0.992], p = 0.047) showed a preventive effect on the risk of gouty attacks. In contrast, non-oily fish intake (ß = 1.08, [95%CI: 0.24~1.92], p = 0.012) and sugar intake (ß = 0.34, [95%CI: 0.03~0.64], p = 0.030) were risk factors for elevated serum uric acid levels, and alcohol intake frequency (OR = 1.422, [95%CI: 1.079~1.873], p = 0.012) was a risk factors for gout predisposition. CONCLUSIONS: These results will significantly contribute to the formulation and refinement of nutritional strategies tailored to patients afflicted with gout.
RESUMEN
Influenza A, the most common subtype, induces 3 to 5 million severe infections and 250,000 to 500,000 deaths each year. Vaccination is traditionally considered to be the best way to prevent influenza A. Yet because the Influenza A virus (IAV) is highly susceptible to antigenic drift and Antigenic shift, and because of the lag in vaccine production, this poses a significant challenge to vaccine effectiveness. Additionally, much information about the resistance of antiviral drugs, such as Oseltamivir and Baloxavir, has been reported. Therefore, the search for alternative therapies in the treatment of influenza is warranted. Recent studies have found that regulating the gut microbiota (GM) can promote the immune effects of anti-IAV via the gut-lung axis. This includes promoting IAV clearance in the early stages of infection and reducing inflammatory damage in the later stages. In this review, we first review the specific alterations in GM observed in human as well as animal models regarding IAV infection. Then we analyzed the effect of GM on host immunity against IAV, including innate immunity and subsequent adaptive immunity. Finally, our study also summarizes the effects of therapies using probiotics, prebiotics, or herbal medicine in influenza A on intestinal microecological composition and their immunomodulatory effects against IAV.
Asunto(s)
Microbioma Gastrointestinal , Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Animales , Humanos , Gripe Humana/tratamiento farmacológico , PulmónRESUMEN
This study presents the first bibliometric evaluation and systematic analysis of publications related to mucosal immunity and commensal microbiota over the last two decades and summarizes the contribution of countries, institutions, and scholars in the study of this field. A total of 1423 articles related to mucosal immunity and commensal microbiota in vivo published in 532 journals by 7774 authors from 1771 institutions in 74 countries/regions were analyzed. The interaction between commensal microbiota in vivo and mucosal immunity is essential in regulating the immune response of the body, maintaining communication between different kinds of commensal microbiota and the host, and so on. Several hot spots in this field have been found to have received extensive attention in recent years, especially the effects of metabolites of key strains on mucosal immunity, the physiopathological phenomena of commensal microbiota in various sites including the intestine, and the relationship between COVID-19, mucosal immunity and microbiota. We hope that the full picture of the last 20 years in this research area provided in this study will serve to deliver necessary cutting-edge information to relevant researchers.