Alleviating effect of vagus nerve cutting in Salmonella-induced gut infections and anxiety-like behavior via enhancing microbiota-derived GABA.

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-1ß, 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.

A synbiotic formulation of Lactobacillus reuteri and inulin alleviates ASD-like behaviors in a mouse model: the mediating role of the gut-brain axis.

Autism Spectrum Disorder (ASD), a complex neurodevelopmental disorder marked by social communication deficits and repetitive behaviors, may see symptom amelioration through gut microbiota modulation. This study investigates the effects of a synbiotic - specifically a probiotic amplified by prebiotic supplementation - on ASD-like mouse model's social deficiencies. This model was established via valproic acid injection into pregnant females. Post-weaning, male progeny received daily synbiotic treatment, a combination of Lactobacillus reuteri (L. reuteri) and inulin, for four weeks. Results indicated that the synbiotic rectified social impairments and attenuated inflammatory cytokine expressions in the brain. Moreover, synbiotic intervention protected gut barrier integrity and altered the gut microbiota composition, enhancing the butyrate-producing Bifidobacterium abundance. The synbiotic elevated metabolites such as butyrate and 3-hydroxybutyric acid (3-HB), alongside upregulated genes associated with 3-HB synthesis in the colon and liver, and brain receptors. Conclusively, the synbiotic combination of L. reuteri and inulin mitigated ASD-related social impairments, partially via their regulatory effect on the gut-brain axis.

High-fiber diet mitigates maternal obesity-induced cognitive and social dysfunction in the offspring via gut-brain axis.

Maternal obesity has been reported to be related to neurodevelopmental disorders in the offspring. However, the underlying mechanisms and effective interventions remain unclear. This cross-sectional study with 778 children aged 7-14 years in China indicated that maternal obesity is strongly associated with children's lower cognition and sociality. Moreover, it has been demonstrated that maternal obesity in mice disrupted the behavior and gut microbiome in offspring, both of which were restored by a high-fiber diet in either dams or offspring via alleviating synaptic impairments and microglial maturation defects. Co-housing and feces microbiota transplantation experiments revealed a causal relationship between microbiota and behavioral changes. Moreover, treatment with the microbiota-derived short-chain fatty acids also alleviated the behavioral deficits in the offspring of obese dams. Together, our study indicated that the microbiota-metabolites-brain axis may underlie maternal obesity-induced cognitive and social dysfunctions and that high dietary fiber intake could be a promising intervention.

Ficus carica polysaccharide attenuates DSS-induced ulcerative colitis in C57BL/6 mice.

The Ficus carica polysaccharide (FCPS) components of the common fig fruit have been demonstrated to exhibit antioxidant and immunity-enhancing activities. However, it is unclear whether it could prevent the ulcerative colitis development. Here, we reported that 5 week orally administered FCPS (150-300 mg per kg bw) significantly prevented DSS-induced colitis in C57BL/6J mice by improving the colon length and suppressing the infiltration of inflammatory cells in the gut. FCPS treatment protected the goblet cells, elevated the expression of tight junction protein claudin-1, and suppressed the formation of cytokines including TNF-α and IL-1ß. FCPS supplementation significantly reformed the gut microbiome by enhancing the abundance of S24-7, Bacteroides, and Coprococus, and suppressing the abundance of Escherichia and Clostridium at the genus level. Consistently, the formation of beneficial microbial metabolites, short chain fatty acids, especially acetate and butyrate, were improved in FCPS-treated colitis mice. The correlation analysis indicated that the protective effects of FCPS on ulcerative colitis might be highly correlated with the microbiota composition changes and the formation of SCFAs. In conclusion, these results indicated that FCPS supplementation could be a promising nutritional strategy for reducing inflammatory bowel disease and the gut microbes play essential roles in providing these beneficial effects.

Effects of alternate-day fasting, time-restricted fasting and intermittent energy restriction DSS-induced on colitis and behavioral disorders.

Intermittent fasting (IF) has been reported to have beneficial effects on improving gut function via lowering gut inflammation and altering the gut microbiome diversity. In this study, we aimed to investigate the differential effects of three different common IF treatments, alternate day fasting (ADF), time-restricted fasting (TRF), and intermittent energy restriction (IER), on a dextran sodium sulfate (DSS)-induced colitis mouse model. The results indicated that TRF and IER, but not ADF improved the survival rates of the colitis mice. TRF and IER, but not ADF, reversed the colitis pathological development by improving the gut barrier integrity and colon length. Importantly, TRF and IER suppressed the inflammatory responses and oxidative stress in colon tissues. Interestingly, TRF and IER also attenuated colitis-related anxiety-like and obsessive-compulsive disorder behavior and alleviated the neuroinflammation and oxidative stress. TRF and IER also altered the gut microbiota composition, including the decrease of the enrichments of colitis-related microbes such as Shigella and Escherichia Coli, and increase of the enrichments of anti-inflammatory-related microbes. TRF and IER also improved the short chain fatty acid formation in colitis mice. In conclusion, the TRF and IER but not ADF exhibited the protective effects against colitis and related behavioral disorders, which could be partly explained by improving the gut microbiome compositions and preventing gut leak, and consequently suppressing the inflammation and oxidative damages in both colon and brain. The current research indicates that proper IF regimens could be effective strategies for nutritional intervention for the prevention and treatment of colitis.

Lycopene supplementation attenuates western diet-induced body weight gain through increasing the expressions of thermogenic/mitochondrial functional genes and improving insulin resistance in the adipose tissue of obese mice.

This passive overconsumption of western diet has precipitated a steep rise in obesity and its comorbidities, and obesity has become one of the main threats to health worldwide. Thus, deciphering the molecular mechanisms leading to obesity is therefore of utmost importance to guide the search for novel therapeutic and preventive strategies. Lycopene (LYC), a major carotenoid present in tomato, has been regarded as a nutraceutical that has powerful anti-oxidant and anti-obesity bioactivities. Even though substantial progress has been made in deciphering the mechanism of how LYC affects obesity in recent years, whether thermogenic genes, mitochondrial function and insulin resistance are involved in the anti-obesity effect of LYC is yet to be elucidated. In the current study, we demonstrated that LYC remarkably suppressed HFFD-elevated mice body weight gain. LYC blocked lipid accumulation in adipose tissue by decreasing the expressions of lipogenesis genes and increasing the expressions of lipidolysis related genes, including thermogenic and mitochondrial functional genes. Moreover, LYC improved HFFD-induced insulin resistance in WATs via inhibiting the inflammation responses in WATs, decreasing circulating proinflammatory cytokines, suppressing gut leak and intestinal inflammation. Our study indicating that the supplementation of LYC might be a nutritional preventive strategy to combat obesity.

Lycopene ameliorates systemic inflammation-induced synaptic dysfunction via improving insulin resistance and mitochondrial dysfunction in the liver-brain axis.

Systemic inflammation is an important determinant of synaptic dysfunction, but the underlying molecular mechanisms remain elusive. Lycopene (LYC), a major carotenoid present in tomato, is regarded as a nutraceutical that has significant antioxidant and anti-obesity bioactivities. In the current study, we randomly divided 3-month-old C57BL/6J mice into 3 groups: the control, LPS and LPS + LYC groups (LYC, 0.03% w/w, mixed with normal chow) for 5 weeks, and then mice were intraperitoneally injected with LPS (0.25 mg kg-1) for 9 days. Our results demonstrated that LYC supplementation effectively attenuated LPS-elicited neuronal damage and synaptic dysfunction through increasing the expressions of neurotrophic factors and the synaptic proteins SNAP-25 and PSD-95. LYC ameliorated LPS-induced insulin resistance and mitochondrial dysfunction in the mouse brain and liver. LYC alleviated the neuroinflammation and hepatic inflammation. Furthermore, LYC decreased the circulating levels of insulin and proinflammatory mediators LPS, TNF-α, IL-1ß and IL-6. In conclusion, these results indicated that the supplementation of LYC might be a nutritional preventive strategy in systemic inflammation-induced synaptic dysfunction.