The role of gut microbiota augmentation in managing non-alcoholic fatty liver disease: an in-depth umbrella review of meta-analyses with grade assessment

Abstract

Background and aim: Currently, there are no authorized medications specifically for non-alcoholic fatty liver disease (NAFLD) treatment. Studies indicate that changes in gut microbiota can disturb intestinal balance and impair the immune system and metabolism, thereby elevating the risk of developing and exacerbating NAFLD. Despite some debate, the potential benefits of microbial therapies in managing NAFLD have been shown.

Methods: A systematic search was undertaken to identify meta-analyses of randomized controlled trials that explored the effects of microbial therapy on the NAFLD population. The goal was to synthesize the existing evidence-based knowledge in this field.

Results: The results revealed that probiotics played a significant role in various aspects, including a reduction in liver stiffness (MD: -0.38, 95% CI: [-0.49, -0.26]), hepatic steatosis (OR: 4.87, 95% CI: [1.85, 12.79]), decrease in body mass index (MD: -1.46, 95% CI: [-2.43, -0.48]), diminished waist circumference (MD: -1.81, 95% CI: [-3.18, -0.43]), lowered alanine aminotransferase levels (MD: -13.40, 95% CI: [-17.02, -9.77]), decreased aspartate aminotransferase levels (MD: -13.54, 95% CI: [-17.85, -9.22]), lowered total cholesterol levels (MD: -15.38, 95% CI: [-26.49, -4.26]), decreased fasting plasma glucose levels (MD: -4.98, 95% CI: [-9.94, -0.01]), reduced fasting insulin (MD: -1.32, 95% CI: [-2.42, -0.21]), and a decline in homeostatic model assessment of insulin resistance (MD: -0.42, 95% CI: [-0.72, -0.11]) (P<0.05).

Conclusion: Overall, the results demonstrated that gut microbiota interventions could ameliorate a wide range of indicators including glycemic profile, dyslipidemia, anthropometric indices, and liver injury, allowing them to be considered a promising treatment strategy.

Keywords: meta-analysis; non-alcoholic fatty liver disease; prebiotic; probiotic; synbiotic; umbrella review.

Graphical abstract

Figure 1

Study selection process.

Figure 2

(A) Forest plot for the relationship between microbial therapy and liver stiffness (LS); (B) forest plot for the relationship between microbial therapy and hepatic steatosis (HS).

Figure 3

(A) Forest plot for the relationship between microbial therapy and weight; (B) forest plot for the relationship between microbial therapy and body mass index (BMI); (C) forest plot for the relationship between microbial therapy and waist circumference (WC); (D) forest plot for the relationship between microbial therapy and waist-to-hip ratio (WHR).

Figure 4

(A) Forest plot for the relationship between microbial therapy and alanine aminotransferase (ALT); (B) forest plot for the relationship between microbial therapy and aspartate aminotransferase (AST); (C) forest plot for the relationship between microbial therapy and gamma-glutamyl transferase (GGT); (D) forest plot for the relationship between microbial therapy and alkaline phosphatase (ALP).

Figure 5

(A) Forest plot for the relationship between microbial therapy and total cholesterol (TC); (B) forest plot for the relationship between microbial therapy and low-density lipoprotein (LDL); (C) forest plot for the relationship between microbial therapy and high-density lipoprotein (HDL); (D) forest plot for the relationship between microbial therapy and triglyceride (TG).

Figure 6

(A) Forest plot for the relationship between microbial therapy and fasting blood sugar (FBS); (B) forest plot for the relationship between microbial therapy and insulin; (C) forest plot for the relationship between microbial therapy and hemoglobin A1c (HbA1c); (D) forest plot for the relationship between microbial therapy and homeostatic model assessment of insulin resistance (HOMA-IR).

Figure 7

(A) Forest plot for the relationship between microbial therapy and tumor necrosis factor-alpha (TNF-α); (B) forest plot for the relationship between microbial therapy and C-reactive protein (CRP); (C) forest plot for the relationship between microbial therapy and interleukin 6 (IL-6).

Figure 8

(A) Forest plot for the relationship between microbial therapy and leptin; (B) forest plot for the relationship between microbial therapy and degree of fat infiltration (DFI); (C) forest plot for the relationship between microbial therapy and body fat mass (BFM).

Figure 9

(A) Total effects of probiotics on non-alcoholic fatty liver disease (NAFLD)-related outcomes; (B) total effects of prebiotics on NAFLD-related outcomes; (C) total effects of synbiotics on NAFLD-related outcomes.

Figure 10

Mechanisms of action of the gut microbiota in patients with non-alcoholic fatty liver disease.