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• Vagotomy mitigates Salmonella-induced systemic infection and anxiety-like behavior. • Vagotomy alleviates the Salmonella-induced gut inflammation and neuroinflammation. • Vagotomy enhanced GABA production and related microbes abundance in the infected mice. • Vagotomy relies on GABA production to alleviate gut inflammation. The vagus nerve, a pivotal link within the gut-brain axis, plays a critical role in maintaining homeostasis and mediating communication between the gastrointestinal tract and the brain. It has been reported that gastrointestinal infection by Salmonella typhimurium (S. typhimurium) triggers gut inflammation and manifests as anxiety-like behaviors, yet the mechanistic involvement of the vagus nerve remains to be elucidated. In this study, we demonstrated that unilateral cervical vagotomy markedly attenuated anxiety-like behaviors induced by S. typhimurium SL1344 infection in C57BL/6 mice, as evidenced by the open field test and marble burying experiment. Furthermore, vagotomy significantly diminished neuronal activation within the nucleus of the solitary tract and amygdala, alongside mitigating aberrant glial cell activation in the hippocampus and amygdala. Additionally, vagotomy notably decreases serum endotoxin levels, counters the increase in splenic Salmonella concentration, and modulates the expression of inflammatory cytokines—including IL-6, IL-1β, and TNF-α—in both the gastrointestinal tract and brain, with a concurrent reduction in IL-22 and CXCL1 expression. This intervention also fostered the enrichment of beneficial gut microbiota, including Alistipes and Lactobacillus species, and augmented the production of gamma-aminobutyric acid (GABA) in the gut. Administration of GABA replicated the vagotomy's beneficial effects on reducing gut inflammation and anxiety-like behavior in infected mice. However, blockade of GABA receptors with picrotoxin abrogated the vagotomy's protective effects against gut inflammation, without influencing its impact on anxiety-like behaviors. Collectively, these findings suggest that vagotomy exerts a protective effect against infection by promoting GABA synthesis in the colon and alleviating anxiety-like behavior. This study underscores the critical role of the vagus nerve in relaying signals of gut infection to the brain and posits that targeting the gut-brain axis may offer a novel and efficacious approach to preventing gastrointestinal infections and associated behavioral abnormalities. [ABSTRACT FROM AUTHOR]

[Display omitted] • MOS alleviates the cognitive deficits and mental disorders in 5xFAD mice. • MOS suppresses neuroinflammation and oxidative stress in the CNS of 5xFAD mice. • MOS balances the HPA axis and norepinephrine levels in serum of 5xFAD mice. • MOS reshapes gut microbiota composition and SCFAs formation in 5xFAD mice. • The gut-brain axis plays a pivotal role in mediating the neuroprotective effects of MOS. Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive deficits and psychiatric symptoms. The gut microbiota-brain axis plays a pivotal role during AD development, which could target nutritional intervention. The prebiotic mannan oligosaccharide (MOS) has been reported to reshape the gut microbiome and enhanced the formation of the neuroprotective metabolites short-chain fatty acids (SCFAs). Here, we found that an 8-week treatment of MOS (0.12%, w / v in the drinking water) significantly improved cognitive function and spatial memory, accompanied by attenuated the anxiety- and obsessive-like behaviors in the 5xFAD transgenic AD mice model. MOS substantially reduced the Aβ accumulation in the cortex, hippocampus, and amygdala of the brain. Importantly, MOS treatment significantly balanced the brain redox status and suppressed the neuroinflammatory responses. Moreover, MOS also alleviated the HPA-axis disorders by decreasing the levels of hormones corticosterone (CORT) and corticotropin-releasing hormone (CRH) and upregulated the norepinephrine (NE) expressions. Notably, the gut barrier integrity damage and the LPS leak were prevented by the MOS treatment. MOS re-constructed the gut microbiota composition, including increasing the relative abundance of Lactobacillus and reducing the relative abundance of Helicobacter. MOS enhanced the butyrate formation and related microbes levels. The correlation analysis indicated that the reshaped gut microbiome and enhanced butyrate formation are highly associated with behavioral alteration and brain oxidative status. SCFAs supplementation experiment also attenuated the behavioral disorders and Aβ accumulation in the AD mice brain, accompanied by balanced HPA-axis and redox status. In conclusion, the present study indicated that MOS significantly attenuates the cognitive and mental deficits in the 5xFAD mice, which could be partly explained by the reshaped microbiome and enhanced SCFAs formation in the gut. MOS, as a prebiotics, can be translated into a novel microbiota-targeted approach for managing metabolic and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Stroke is a worldwide concern due to its high disability and mortality rates, especially in many countries entering ageing societies. This study aims to understand the spatial heterogeneity of stroke onset and residential environment influence scopes from multiscale. The 2013 to 2022 spatiotemporal distribution pattern of stroke onset was obtained via out-patient data from a hospital in Shanghai. Then nine residential environmental factors were selected to estimate the association of stroke onset by multiscale geographically weighted regression (MGWR), in three scenarios. Accessibility to pubs/bars (PUB) and building density (BD) were the top two residential environmental factors both for the entire sample and by gender. Stress-related environmental factors have a greater impact on the onset of stroke in men but are limited in scope. The population of elderly people have relevance to environmental variables heterogeneity. The indicators relating to unhealthy food and alcohol suggest that habit-inducing environmental factors have a limited impact on stroke onset, but rather that pre-existing habits play a greater role. MGWR analyses individual components across multiple bandwidths, revealing geographical disparities in the impact of elements that would otherwise be undetected on a global scale. Environmental factors have a limited impact on the onset of stroke. When society is faced with both heavy ageing and fiscal constraints, some of the blue-green space budgets can be scaled back to invest in more secure facilities. • Relationship between stroke onset and residential environmental factors explored by MGWR. • Accessibility to pub and building density are the top two factors, for the entire sample and by gender. • Males are more affected by stress-related factors; females are more sensitive to PR. • Respond to ageing city development and rationally allocate urban blue-green space. • Promote good living habits from top to bottom to reduce the potential stroke risk. [ABSTRACT FROM AUTHOR]