The effect of increasing intestinal short-chain fatty acid concentration on gut permeability and liver injury in the context of liver disease: A systematic review

Background and Aim The gut barrier protects the liver through tight junctions, which are disrupted in liver disease either from dysbiosis, inflammation, or the effects of ingested compounds such as alcohol. Strengthening of the gut barrier may ameliorate liver injury of varying etiologies. Short chain fatty acids (SCFAs) have been shown to improve gut barrier function. This systematic review aims to synthesize all studies that have trialed SCFA supplementation as a therapy for liver disease. Methods A systematic review assessing the impact of SCFA supplementation on liver injury and intestinal permeability was conducted. All forms of intervention that specifically increased intestinal SCFA concentration and measured both liver injury and permeability were eligible. Two independent reviewers assessed each study for outcomes, risk of bias, and quality using checklists relevant to the study's methodology. Results Seventeen studies were identified; two utilized a human model (15 murine). Fifty-eight markers of liver injury were identified, with 26 different measures of permeability. Given the numerous designs, no meta-analysis was possible. SCFA supplements included oral and enteral butyrate, probiotics, and prebiotics. Fourteen studies demonstrated improved permeability. All studies showed a significant amelioration of liver injury. Conclusions Short chain fatty acid supplementation to reduce intestinal permeability represents a potential therapy in a variety of liver disease models. A large number of outcome measures were reported however not all are practical in human studies. Future work should evaluate methods to increase luminal SCFA concentrations and the effect of this on gut permeability and liver inflammation in people with liver disease.