Increased evidence shows that gut microbiota acts as the primary regulator of the liver; however, its role in sepsis-related liver injury (SLI) in the elderly is unclear. This study assessed whether metformin could attenuate SLI by modulating gut microbiota in septic-aged rats. Cecal ligation and puncture (CLP) was used to induce SLI in aged rats. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. The composition of gut microbiota was analysed by 16S rRNA sequencing. Moreover, the liver and colon tissues were analysed by histopathology, immunofluorescence, immunohistochemistry, and reverse transcription polymerase chain reaction (RT–PCR). Metformin improved liver damage, colon barrier dysfunction in aged SLI rats. Moreover, metformin improved sepsis-induced liver inflammation and damage under gut microbiota. Importantly, FMT assay showed that rats gavaged with faeces from metformin-treated SLI rats displayed less severe liver damage and colon barrier dysfunctions than those gavaged with faeces from SLI rats. The gut microbiota composition among the sham-operated, CLP-operated and metformin-treated SLI rats was different. In particular, the proportion of Klebsiella and Escherichia_Shigella was higher in SLI rats than sham-operated and metformin-treated SLI rats; while metformin could increase the proportion of Bifidobacterium , Muribaculaceae , Parabacteroides_distasonis and Alloprevitella in aged SLI rats. Additionally, Klebsiella and Escherichia_Shigella correlated positively with the inflammatory factors in the liver. Our findings suggest that metformin may improve liver injury by regulating the gut microbiota and alleviating colon barrier dysfunction in septic-aged rats, which may be an effective therapy for SLI.
ObjectiveCorticosteroids are a common option used in sepsis treatment. However, the efficacy and potential risk of corticosteroids in septic patients have not been well assessed. This review was performed to assess the efficacy and safety of corticosteroids in patients with sepsis.MethodsPubMed, Embase, and Cochrane library databases were searched from inception to March 2021. Randomized controlled trials (RCTs) that evaluated the effect of corticosteroids on patients with sepsis were included. The quality of outcomes in the included articles was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation methodology. The data were pooled by using risk ratio (RR) and mean difference (MD). The random-effects model was used to evaluate the pooled MD or RR and 95% confidence intervals (CIs).ResultsFifty RCTs that included 12,304 patients with sepsis were identified. Corticosteroids were not associated with the mortality in 28-day (RR, 0.94; 95% CI, 0.87–1.02; evidence rank, moderate) and long-term mortality (>60 days) (RR, 0.96; 95% CI, 0.88–1.05) in patients with sepsis (evidence rank, low). However, corticosteroids may exert a significant effect on the mortality in the intensive care unit (ICU) (RR, 0.9; 95% CI, 0.83–0.97), in-hospital (RR, 0.9; 95% CI, 0.82–0.99; evidence rank, moderate) in patients with sepsis or septic shock (evidence rank, low). Furthermore, corticosteroids probably achieved a tiny reduction in the length of hospital stay and ICU. Corticosteroids were associated with a higher risk of hypernatremia and hyperglycemia; furthermore, they appear to have no significant effect on superinfection and gastroduodenal bleeding.ConclusionsCorticosteroids had no significant effect on the 28-day and long-term mortality; however, they decreased the ICU and hospital mortality. The findings suggest that the clinical corticosteroids may be an effective therapy for patients with sepsis during the short time.Systematic Review Registrationhttps://inplasy.com/wp-content/uploads/2021/05/INPLASY-Protocol-1074-4.pdf
Sepsis-associated encephalopathy (SAE) is often associated with increased ICU occupancy and hospital mortality and poor long-term outcomes, with currently no specific treatment. Pathophysiological mechanisms of SAE are complex and may involve activation of microglia, multiple intracranial inflammatory factors, and inflammatory pathways. We hypothesized that metformin may have an effect on microglia, which affects the prognosis of SAE. In this study, metformin treatment of mice with SAE induced by lipopolysaccharide (LPS) reduced the expression of microglia protein and related inflammatory factors. Poor prognosis of SAE is related to increased expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) in brain tissues. Levels of inflammatory cytokines produced by LPS-induced SAE mouse microglia were significantly increased compared with those in the sham group. In addition, ionized calcium-binding adapter molecule 1 (Iba-1) was significantly reduced in metformin-treated SAE mice compared with untreated SAE mice, suggesting that metformin can reduce microgliosis and inhibit central nervous system inflammation, thereby improving patient outcomes. In conclusion, our results stipulate that metformin inhibits inflammation through the adenosine 5 ′ -monophosphate (AMP-) activated protein kinase pathway by inhibiting nuclear factor kappa beta (NF-κB). Metformin can partially reverse the severe prognosis caused by sepsis by blocking microglial proliferation and inhibiting the production of inflammatory factors.
Objective: Corticosteroids are a common option used in the treatment of sepsis. However, the efficacy and potential risk of corticosteroids in septic patients have not been well assessed. We performed this review to assess the efficacy and safety of corticosteroids in sepsis patients.Methods: We searched the PubMed, Embase, and Cochrane library databases from inception to March 2021. Randomized controlled trials (RCTs) that evaluated the effect of corticosteroids on septic patients were included. The quality of outcomes in the included articles was evaluated using the Grading of Recommendations Assessment, Development and Evaluation methodology. The data were pooled by using relative risk (RR) and mean difference (MD). The random-effects model were used to to eveluate the pooled MD or RR and 95% CI.Results: Fifty-three RCTs that included 12,310 patients with sepsis were identified. Corticosteroids were not associated with the mortality in 28-day (RR, 0.94; 95% CI, 0.87–1.02; evidence rank, moderate), and long-term mortality (>60 d) (RR, 0.96; 95% CI, 0.88–1.05) in septic patients (evidence rank, low). However, corticosteroids may exert a significant effect on the mortality in ICU (RR, 0.89; 95% CI, 0.80–0.98), in-hospital (RR, 0.93; 95% CI, 0.88–0.99; evidence rank, moderate) in patients with sepsis or septic shock (evidence rank, low). Furthermore, corticosteroids probably achieved a very small reductions in the length of hospital stay and ICU. Corticosteroids were associated with an higher risk of hypernatremia and hyperglycemia; further, they appear to have no significant effect on superinfection and gastroduodenal bleeding.Conclusions: Corticosteroids had no significant effect on the 28 and long-term mortality; however, they decreased the ICU and hospital mortality. Further, corticosteroids could increase the risk of the hypernatremia and hyperglycemia in sepsis patients.
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