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Published on: December 18, 2010
Metformin attenuated sepsis-related liver injury by modulating gut microbiota
Huoyan Liang1,2, Heng Song1,2, Xiaojuan Zhang1
1General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, People's Republic of China.
Abstract:
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.
Insights
Metformin treatment improved liver injury and gut barrier function in aged rats with sepsis. This suggests metformin may be an effective therapy for sepsis-related liver injury by modulating gut microbiota.
Area of Science:
- Hepatology
- Gastroenterology
- Microbiology
Background:
- The gut microbiota significantly influences liver health, but its role in sepsis-related liver injury (SLI) in elderly individuals remains poorly understood.
- Sepsis-related liver injury (SLI) poses a significant health challenge, particularly in aging populations.
Purpose of the Study:
- To investigate the potential of metformin in attenuating SLI in aged rats.
- To determine if metformin's effects are mediated by modulating the gut microbiota.
Main Methods:
- Sepsis-related liver injury (SLI) was induced in aged rats using cecal ligation and puncture (CLP).
- Metformin was administered to assess its therapeutic effects.
- Fecal microbiota transplantation (FMT) was employed to confirm the role of gut microbiota.
- Gut microbiota composition was analyzed using 16S rRNA sequencing.
- Liver and colon tissues were examined via histopathology, immunofluorescence, immunohistochemistry, and RT-PCR.
Main Results:
- Metformin treatment significantly improved liver damage and colon barrier dysfunction in aged SLI rats.
- FMT from metformin-treated rats reduced liver damage and colon barrier dysfunction in recipients, confirming the microbiota's role.
- Metformin altered gut microbiota composition, increasing beneficial bacteria like *Bifidobacterium* and decreasing detrimental bacteria such as *Klebsiella* and *Escherichia_Shigella*.
- *Klebsiella* and *Escherichia_Shigella* positively correlated with liver inflammatory markers.
Conclusions:
- Metformin demonstrates a therapeutic potential for sepsis-related liver injury in aged individuals.
- Modulation of gut microbiota and alleviation of colon barrier dysfunction are key mechanisms by which metformin exerts its protective effects on the liver.
- Metformin represents a promising therapeutic strategy for managing SLI in the elderly.
