Alcohol abuse triggers neuroinflammation, leading to neuronal damage and further memory and cognitive impairment. Few satisfactory advances have been made in the management of alcoholic central nervous impairment. Therefore, novel and more practical treatment options are urgently needed. Butyrate, a crucial metabolite of short-chain fatty acids (SCFAs), has been increasingly demonstrated to protect against numerous metabolic diseases. However, the impact of butyrate on chronic alcohol consumption-induced central nervous system (CNS) lesions remains unknown. In this study, we assessed the possible effects and underlying mechanisms of butyrate on the attenuation of alcohol-induced CNS injury in mice. Firstly, sixty female C57BL/6 J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with sodium butyrate (NaB) group (PF/NaB) and AF with NaB group (AF/NaB). Each group was fed a modified Lieber-DeCarli liquid diet with or without alcohol. After six weeks of feeding, the mice were euthanized and the associated indicators were investigated. As indicated by the behavioral tests and brain morphology, dietary NaB administration significantly ameliorated aberrant behaviors, including locomotor hypoactivity, anxiety disorder, depressive behavior, impaired learning, spatial recognition memory, and effectively reduced chronic alcoholic central nervous system damage. To further understand the underlying mechanisms, microglia-mediated inflammation and the associated M1/M2 polarization were measured separately. Firstly, pro-inflammatory TNF-α, IL-1β, and IL-6 in brain and peripheral blood circulation were decreased, but IL-10 were increased in the AF/NaB group compared with the AF/CON group. Consistently, the abnormal proportions of activated and resting microglial cells in the hippocampus and cortex regions after excessive alcohol consumption were significantly reduced with NaB treatment. Moreover, the rectification of microglia polarization (M1/M2) imbalance was found after NaB administration via binding GPR109A, up-regulating the expression of PPAR-γ and down-regulating TLR4/NF-κB activation. In addition to the direct suppression of neuroinflammation, intriguingly, dietary NaB intervention remarkably increased the levels of intestinal tight junction protein occludin and gut morphological barrier, attenuated the levels of serum lipopolysaccharide (LPS) and dysbiosis of gut microbiota, suggesting that NaB supplementation effectively improved the integrity and permeability of gut microecology. Finally, the neurotransmitters including differential Tryptophan (Trp) and Kynurenine (Kyn) were found with dietary NaB administration, which showed significantly altered and closely correlated with the gut microbiota composition, demonstrating the complex interactions in the microbiome-gut-brain axis involved in the efficacy of dietary NaB therapy for alcoholic CNS lesions. Dietary microbial metabolite butyrate supplementation ameliorates chronic alcoholic central nervous damage and improves related memory and cognitive functions through suppressing microglia-mediated neuroinflammation by GPR109A/PPAR-γ/TLR4-NF-κB signaling pathway and modulating microbiota-gut-brain axis.

The microbiome–gut–brain (MGB) axis, which regulates neurological and cognitive functions, plays an essential role in schizophrenia (SCZ) progression. Dietary inulin could be a novel strategy for the treatment of SCZ due to its modulating effects on the gut microbiota. In this study, the effects of inulin on mice with SCZ were studied. As indicated by the behavioural tests, expression of neurotransmitters, inflammatory indicators, and brain morphology, inulin administration ameliorated aberrant behaviours (locomotor hypoactivity, anxiety disorders and depressive behaviours, and impaired learning and spatial recognition memory) and effectively reduced neuroinflammation and neuronal damage. In addition, inulin improved intestinal integrity and permeability, as indicated by the elevated expression of tight junction proteins (p < 0.05). The results of 16S rRNA sequencing and analysis showed that inulin increased the abundance of Lactobacillus and Bifidobacterium, which were negatively correlated with 5-hydroxytryptamine and inflammatory cytokines and positively correlated with brain-derived neurotrophic factor (BDNF). Inulin caused a reduction in Akkermansia that was positively correlated with inflammatory cytokines and negatively correlated with BDNF. These results suggested that dietary inulin modulated the gut microbiota and exerted anti-inflammatory effects in mice though the MGB axis, which further ameliorated SCZ. Therefore, the results of this study provide a potential explanation for inulin intervention in the treatment of SCZ.

This study aimed to explore the relationship between stressful life events, coping styles, and schizophrenia relapse. The sample for this study included 248 patients with schizophrenia from a psychiatric outpatient clinic in Hunan Province, China. Stressful life events, occurrence of schizophrenia relapse, and coping style were assessed by the Scale for the Social Readjustment Rating, Brief Psychiatric Rating Scale, and Simplified Coping Style Questionnaire, respectively. Spearman correlation analysis and binary logistic regression analysis were adopted to explore the relationships among coping styles, schizophrenia relapse, and stressful life events. Stressful life events and negative coping exhibited significant positive association with schizophrenia relapse, while positive coping exhibited a significant negative association with schizophrenia relapse. Stressful life events and positive coping exerted significant effects on schizophrenia relapse, while negative coping did not. We also found that both positive coping and negative coping have moderating effects on the relationship between stressful life events and schizophrenia relapse, but the relationship is weak. The study highlighted the importance of interventions designed to reduce stressful life events, promote positive coping, and address negative coping in patients with schizophrenia.

Purpose: Several studies have explored the relationship between level of education and medication adherence, as well as the relationship between level of education and cognitive function. However, there have been few studies on the relationships between level of education, cognitive function, and medication adherence. This study aimed to explore whether cognitive function has a mediating effect between level of education and medication adherence in patients with schizophrenia. Patients and Methods: A total of 329 participants were included in this study. Cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia, and medication adherence using the Medication Adherence Questionnaire. The relationships between the clinical factors and cognitive function that contributed to medication adherence were tested through multivariable linear regression analysis. The mediating effect of medication adherence was tested using the bootstrapping approach with the PROCESS macro. Results: Family history, insight and executive function were associated with medication adherence in individuals with schizophrenia, and executive function had a mediating effect between level of education and medication adherence. Conclusion: Adopting specific education programs that promote cognitive development as well as actively intervening in executive function might be conducive to improve medication adherence in patients with schizophrenia.