Background Accumulating evidence indicates that high-fat diet (HFD)-induced metabolic disorders are associated with dysbiosis of the gut microbiota. However, the sex-specific characteristics of the gut microbiota and its association with a sexually dimorphic response to a HFD remain unclear. Methods Male and female mice were randomly assigned to receive a chow diet (CD) or HFD for 12 weeks. A group of HFD mice were pretreated with antibiotic cocktails for 4 weeks. Body weight, insulin sensitivity and the levels of serum metabolic parameters (blood glucose and insulin) were evaluated. 16S rRNA gene sequencing was performed to analyze the composition of the gut microbiota. Results HFD-induced body weight gain (BWG) was higher in male mice than in female mice. While insulin resistance was increased in the HFD group compared to CD group in male mice, there was no difference in insulin resistance among female mice. Antibiotic-pretreatment alleviated HFD-induced insulin resistance in male mice and elevated fasting blood glucose in female mice. The composition of the gut microbiota in male mice was remarkably different from that in female mice independent of diet. A higher abundance of the genera Parabacteroides, Lactobacillus, Bacteroides, and Bifidobacterium was observed in females than inmales. HFD feeding also influenced the structure of the gut microbiota, as it decreased the abundance of short-chain fatty acids-producing bacteria including Roseburia and Lachnospiraceae_NK4A136_group. Alterations in the gut microbiota in response to antibiotics followed by HFD were different between males and females, indicating sex-dependent sensitivity to antibiotics. Conclusions We identified that sex had a greater impact on the composition of gut microbiota than environmental factors (HFD and antibiotics). The enrichment of beneficial microbes in female mice may be associated with the resistance of female mice to HFD-induced metabolic disorders, which was weakened by antibiotic pretreatment.

AMD3100 is a specific C-X-C chemokine receptor type 4 (CXCR4) antagonist which blocks the interaction between CXCR4 and CXCL12. Multiple lines of evidence suggest that AMD3100 has analgesic effects on many pathological pain states, including peripheral neuropathic pain. However, little is known about the underlying mechanisms. In the current study, we investigated the effect of different doses of AMD3100 on neuropathic pain in rats after L5 spinal nerve ligation. We used naloxone methiodide (NLXM) to further determine whether AMD3100-mediated analgesic effect was opioid-dependent. Behavioral study showed that early repeated administration of AMD3100 (2 and 5 mg/kg, i.p.) dose-dependently alleviates peripheral neuropathic pain. Flow cytometry, immunofluorescence and NLXM experiments showed that AMD3100 alleviates neuropathic pain partially by augmenting leukocyte-derived endogenous opioid secretion. Furthermore, we found that pro-inflammatory cytokines were down-regulated by AMD3100 using Enzyme-linked Immunosorbent Assay. Our data indicate that AMD3100 dose-dependently alleviates neuropathic pain partially by augmenting leukocyte-derived endogenous opioid secretion. This finding suggests that AMD3100 may be a viable pharmacotherapeutic strategy for the treatment of neuropathic pain.

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Our data indicate that propofol anesthesia promotes the restoration of disturbed excitatory and inhibitory neurotransmitter release in the hippocampus after PSD, similar to the beneficial effects of natural sleep. This finding suggests that propofol anesthesia may be a viable pharmacotherapeutic strategy for the treatment of certain sleep disorders that share similar mechanisms with PSD.