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Therapeutic Evaluation of Fecal Microbiota Transplantation in an Interleukin 10-Deficient Mouse Model
Published on: April 6, 2022
Gut microbiota links to infection in liver transplantation
Chad Hinkle1, Daniel Friedman1, Christopher J Lehmann1,2
1Biological Sciences Division, Department of Medicine, Section of Infectious Diseases and Global Health.
Purpose Of Review:
Infectious complications remain a major source of morbidity and mortality following liver transplantation, with Enterococcus spp. and Enterobacterales among the most common causative pathogens. Increasing evidence suggests that the intestinal microbiota plays a central role in regulating susceptibility to these infections through maintenance of colonization resistance, epithelial barrier integrity, and host immune signaling.
Recent Findings:
Patients with end-stage liver disease frequently develop intestinal dysbiosis characterized by reduced microbial diversity, depletion of obligate anaerobes, and expansion of pathobionts prior to transplantation. Liver transplantation further exacerbates these disruptions through perioperative antibiotics, surgical injury, ischemia-reperfusion injury, altered bile acid metabolism, and immunosuppressive therapy. Recent studies have demonstrated associations between loss of microbial diversity, depletion of beneficial microbial metabolites, including short-chain fatty acids and secondary bile acids, and subsequent postoperative infections in liver transplant recipients. These findings suggest that the microbiome may function both as a mechanistic mediator and biomarker of infection risk.
Summary:
Mechanisms of colonization resistance, microbiome-mediated maintenance of the intestinal barrier, and the emergence of pathobiont domination, are critical in the development of infection following liver transplant and requires strategies to diagnose and therapeutically restore microbiome function to avoid infection.
Insights
Liver transplant recipients with intestinal dysbiosis face higher infection risks. Restoring gut microbiome function is crucial for preventing post-transplant infections and improving outcomes.
Area of Science:
- Gastroenterology and Hepatology
- Microbiology
- Transplantation Immunology
Background:
- Infectious complications are a significant cause of morbidity and mortality after liver transplantation.
- Enterococcus spp. and Enterobacterales are common pathogens in these infections.
- The intestinal microbiota is increasingly recognized for its role in preventing infections via colonization resistance, barrier integrity, and immune signaling.
Purpose of the Study:
- To review the role of the intestinal microbiota in infectious complications following liver transplantation.
- To explore how dysbiosis impacts infection risk in liver transplant recipients.
- To highlight potential therapeutic strategies targeting the microbiome.
Main Methods:
- Review of recent studies on the gut microbiome in liver transplant recipients.
- Analysis of associations between microbial composition, metabolites, and postoperative infections.
- Examination of mechanisms of dysbiosis and pathobiont emergence.
Main Results:
- End-stage liver disease patients often exhibit pre-transplant intestinal dysbiosis (reduced diversity, depleted anaerobes, pathobiont expansion).
- Liver transplantation exacerbates dysbiosis due to antibiotics, surgery, and immunosuppression.
- Loss of microbial diversity and beneficial metabolites correlates with increased postoperative infection risk.
Conclusions:
- Colonization resistance and microbiome-maintained intestinal barrier function are critical for preventing post-transplant infections.
- Pathobiont dominance contributes to infection development.
- Strategies to diagnose and restore microbiome function are needed to mitigate infection risk.
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