The Benefit of Probiotics in Pediatric Nonalcoholic Fatty Liver Disease: A Meta-analysis of Randomized Control Trials

Abstract

Objectives: We conducted a systematic review and meta-analysis to provide a summary of the current literature about the efficacy of probiotics in pediatric nonalcoholic fatty liver disease (NAFLD). Methods: A systematic literature search through major electronic databases was carried out for RCTs till September 9, 2021, investigating the efficacy of probiotics in the treatment of pediatric patients with NAFLD. Weighted mean differences (WMD) and Standard Deviations (SD) were used to calculate continuous outcomes and a Risk Ratio with 95% CI was used for dichotomous outcomes. Results: In total, 4 RCTs with 238 pediatric patients with NAFLD were included in the study. Probiotic supplementation revealed a statistically significant difference in transaminases' levels (ALT: WMD = -7.51 IU/L, 95% CI, -11.28 to -3.73, I 2 = 0%, P < 0.0001; AST: WMD = -6.46 IU/L, 95% CI, -9.31 to -3.61, I 2 = 0%, P < 0.00001), anthropometric characteristics, total cholesterol, triglycerides and ultrasonographic steatosis improvement. Conclusions: According to the data of this meta-analysis, probiotic supplementation, and especially supplementation of Lactobacillus acidophilus in combination with other strains of Bifidobacterium or Lactobacillus may be beneficial in the improvement of transaminases', lipid parameters' levels, ultrasonographic, and anthropometric characteristics in children with NAFLD. Current evidence does not allow specifying the exact beneficial strain of probiotics mentioned above. The possible effect of probiotics on liver histology improvement in pediatric NAFLD should be examined in future studies.

Updates in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Children

“…The study was limited with small group numbers and a short follow up of 12 weeks. The study showed agreement with earlier studies included in a systematic review (81–83). Overall, there remains a paucity of robust evidence to recommend use of a particular probiotic for the management of MAFLD.…”

The Gut–Liver Axis in Pediatric Liver Health and Disease

“…These findings are also consistent with a slightly smaller-scale study in which 22 children with NAFLD who received the VSL#3 probiotic (containing four strains of Lactobacillus , three strains of Bifidobacterium , and one strain of Streptococcus ) for four months had improvement in their disease based on liver ultrasound findings compared to children who received a placebo [ 47 ]. Most promisingly, a meta-analysis of these aforementioned studies as well as two other randomized control trials including a total of 238 pediatric patients with NAFLD revealed a significant improvement in liver transaminases, total cholesterol, triglyceride levels, and ultrasound findings suggestive of liver steatosis in patients who received probiotics compared to those who did not [ 48 ]. However, heterogeneous strains were used in these studies, and long-term benefits of these probiotics for pediatric NAFLD, as well as the underlying mechanisms of protection, remain to be further investigated.…”

Challenges in pediatric inherited/metabolic liver disease: Focus on the disease spectrum, diagnosis and management of relatively common disorders

“…Similarly, omega-3 fatty acid supplementation was not effective in inducing a significant reduction in ALT or improving liver steatosis on ultrasonography[ 73 ]. Some randomized controlled trials indicated that probiotic supplementation might be beneficial in children with NAFLD, but the current evidence does not specify the exact beneficial strain of probiotics, requiring further studies[ 74 ]. Interestingly, the strategy of targeting the lysosome has seemed to encourage a new direction for future NAFLD treatment, e.g.…”