Brett R Loman1,2, Diego Hernández-Saavedra3, Ruopeng An4, R Scott Rector5. 1. Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, Urbana-Champaign, Illinois. 2. Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA. 3. Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, Urbana-Champaign, Illinois, USA. 4. Department of Kinesiology and Community Health, College of Applied Health Sciences, University of Illinois at Urbana-Champaign, Champaign, Illinois, USA. 5. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Nutrition and Exercise Physiology, University of Missouri-Columbia, Columbia, Missouri, USA.
Abstract
Context: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent and underdiagnosed comorbidity of many chronic diseases that is associated with altered intestinal bacterial communities. This association has prompted research into alternative treatments aimed at modulating intestinal microbiota. Given the novelty of these treatments, scarce evidence regarding their effectiveness in clinical populations exists. Objective: This meta-analysis sought to systemically review and quantitatively synthesize evidence on prebiotic, probiotic, and synbiotic therapies for patients with NAFLD in randomized controlled trials. Data sources: PRISMA guidelines ensured transparent reporting of evidence. PICOS criteria defined the research question for the systematic review. A systematic keyword search in PubMed and EMBASE identified 25 studies: 9 assessed prebiotic, 11 assessed probiotic, and 7 assessed symbiotic therapies for a total of 1309 patients. Data extraction: Basic population characteristics, the primary variables of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (utilized for NAFLD diagnosis), and the secondary variables of body mass index (BMI), gamma-glutamyl transferase (γ-GT), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglyceridges (TAG) were extracted. Pooled effect sizes of these variables were calculated by meta-analysis. No publication bias was identified using Begg's and Egger's tests or Cochrane bias assessment tool. Results: Meta-analysis indicated that microbial therapies significantly reduced BMI (-0.37 kg/m2; 95% confidence interval [CI], -0.46 to -0.28; P < 0.001), hepatic enzymes (ALT, -6.9 U/L [95%CI, -9.4 to -4.3]; AST, -4.6 U/L [95%CI, -6.6 to -2.7]; γ-GT, -7.9 U/L [95%CI, -11.4 to -4.4]; P < 0.001), serum cholesterol (-10.1 mg/dL 95%CI, -13.6 to -6.6; P < 0.001), LDL-c (-4.5 mg/dL; 95%CI, -8.9 to -0.17; P < 0.001), and TAG (-10.1 mg/dL; 95%CI, -18.0 to -2.3; P < 0.001), but not inflammation (TNF-α, -2.0 ng/mL; [95%CI, -4.7 to 0.61]; CRP, -0.74 mg/L [95%CI, -1.9 to 0.37]). Subgroup analysis by treatment category indicated similar effects of prebiotics and probiotics on BMI and liver enzymes but not total cholesterol, HDL-c, and LDL-c. Conclusion: This meta-analysis supports the potential use of microbial therapies in the treatment of NAFLD and sheds light on their potential mode of action. Further research into these treatments should consider the limitations of biomarkers currently used for the diagnosis and progression of NAFLD, in addition to the inherent challenges of personalized microbial-based therapies.
Context:Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent and underdiagnosed comorbidity of many chronic diseases that is associated with altered intestinal bacterial communities. This association has prompted research into alternative treatments aimed at modulating intestinal microbiota. Given the novelty of these treatments, scarce evidence regarding their effectiveness in clinical populations exists. Objective: This meta-analysis sought to systemically review and quantitatively synthesize evidence on prebiotic, probiotic, and synbiotic therapies for patients with NAFLD in randomized controlled trials. Data sources: PRISMA guidelines ensured transparent reporting of evidence. PICOS criteria defined the research question for the systematic review. A systematic keyword search in PubMed and EMBASE identified 25 studies: 9 assessed prebiotic, 11 assessed probiotic, and 7 assessed symbiotic therapies for a total of 1309 patients. Data extraction: Basic population characteristics, the primary variables of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (utilized for NAFLD diagnosis), and the secondary variables of body mass index (BMI), gamma-glutamyl transferase (γ-GT), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglyceridges (TAG) were extracted. Pooled effect sizes of these variables were calculated by meta-analysis. No publication bias was identified using Begg's and Egger's tests or Cochrane bias assessment tool. Results: Meta-analysis indicated that microbial therapies significantly reduced BMI (-0.37 kg/m2; 95% confidence interval [CI], -0.46 to -0.28; P < 0.001), hepatic enzymes (ALT, -6.9 U/L [95%CI, -9.4 to -4.3]; AST, -4.6 U/L [95%CI, -6.6 to -2.7]; γ-GT, -7.9 U/L [95%CI, -11.4 to -4.4]; P < 0.001), serum cholesterol (-10.1 mg/dL 95%CI, -13.6 to -6.6; P < 0.001), LDL-c (-4.5 mg/dL; 95%CI, -8.9 to -0.17; P < 0.001), and TAG (-10.1 mg/dL; 95%CI, -18.0 to -2.3; P < 0.001), but not inflammation (TNF-α, -2.0 ng/mL; [95%CI, -4.7 to 0.61]; CRP, -0.74 mg/L [95%CI, -1.9 to 0.37]). Subgroup analysis by treatment category indicated similar effects of prebiotics and probiotics on BMI and liver enzymes but not total cholesterol, HDL-c, and LDL-c. Conclusion: This meta-analysis supports the potential use of microbial therapies in the treatment of NAFLD and sheds light on their potential mode of action. Further research into these treatments should consider the limitations of biomarkers currently used for the diagnosis and progression of NAFLD, in addition to the inherent challenges of personalized microbial-based therapies.
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