See “Effects of Probiotics on Nonalcoholic Fatty Liver Disease in Obese Children and Adolescents” by Famouri et al on page 413.
With the dramatic widespread increase of obesity over the past few years, nonalcoholic fatty liver disease (NAFLD) has become the main chronic liver disease among children and adults worldwide. Although NAFLD has recently received considerable attention from the scientific community, the knowledge of the mechanisms underlying its development and progression remains a major challenge. In this regard, recent data support the view that the interaction between the liver and gut, the so called “gut-liver axis,” may play a major role among the factors promoting a phenotypic switching from the NAFL state to a more aggressive disease including nonalcoholic steatohepatitis (NASH) and NASH-related fibrosis (1,2). Indeed, several studies in humans have shown an increased intestinal permeability may contribute to liver disease progression through an increased exposure of the liver to gut-derived bacterial products (3). Moreover, recent reports have revealed an important role for altered gut microbiota composition in promoting NAFLD in children (4).
Therefore, modulating gut microbiota with probiotics, prebiotics, and synbiotics has become an attractive treatment strategy of obesity and NAFLD, with some experimental studies confirming the potential value of this approach (5).
In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Famouri et al (6) report the results of their randomized triple-blind trial study on the effects of some probiotics on sonographic and biochemical NAFLD in children. Patients were randomly allocated to receive a mixture probiotic formula or placebo for 12 weeks. The probiotic capsule contained Lactobacillus acidophilus ATCC B3208, 3 × 109 colony forming units (CFU); Bifidobacterium lactis DSMZ 32269, 6 × 109 CFU; B bifidum ATCC SD6576, 2 × 109 CFU; and L rhamnosus DSMZ 21690, 2 × 109 CFU. At the trial end mean of waist circumference, aspartate aminotransferase, alanine aminotransferase, cholesterol, low-density lipoprotein cholesterol, and triglycerides decreased in the intervention group. Moreover, liver sonography normalized in 53.1% and 16.5% of patients in the intervention and placebo groups, respectively. Based on their results, the authors emphasized the effectiveness of their probiotic compound in improving NAFLD in the investigated subjects. The study by Famouri et al is affected by some limitations including the small sample size, short duration of trial and follow-up, and lack of assessment of inflammatory factors, which make the obtained results prone to under- or overestimation.
Moreover, the same strain of probiotic is claimed sometimes not to be active in other populations. That's why we believe these results should need to get confirmatory evidences from more different studies.
The present study is, however, on the line of other reports that have evaluated the efficacy of probiotics in the treatment of NAFLD, finding a good agreement because there is still no truly effective drug treatment. In a double-blind clinical trial, Vajro et al (7) showed that serum alanine aminotransferase markedly decreased (and normalized in 80% of cases) in obese children with NAFLD following Lactobacillus GG administration. Alisi et al, in a randomized double blind trial, recently showed that VSL#3, a probiotic mixture, led to significant improvement in fatty liver severity in obese children with biopsy-proven NASH, as assessed by ultrasound. In addition, these authors found that the patients on VSL#3 had a significant decrease in their body mass index, compared with placebo. It was suggested that supplement of VSL#3 led to weight loss through correction of dysbiosis (8).
More recently, Del Chierico et al showed an altered gut microbiota profile in children with NAFLD compared with controls. The present study was performed by using a recently developed systems biology approach, able to integrate gut microbiota-targeted metagenomics, metabolomics data, and clinical phenomic parameters into a multilayered system of “integrated-omics,” data. Patients had a significant increase in Actinobacteria, whereas Bacteroidetes were reduced. The authors suggested that changes in the gut microbiota profile are associated with disease severity. It is tempting to suggest that in the complex scenario of NAFLD disease, both microbial composition and metabolomic profile can make a signature changing during disease progression (4). These features may also foreshadow a sort of metabolic diagnostic profile specific of steatosis, and thus suggesting a first-line probiotic approach for treating NAFLD. Obviously these promising results need to be extended to a larger pediatric population.
The study of Famouri et al adds another piece to the recently held view that supports the use of probiotics for treating obesity-related NAFLD. This strategy could be suggested in patients who did not have complete success with lifestyle and dietary changes. Finally, on the light of the recent insights on the gut microbiota-liver axis, future trials involving the use of probiotics in NAFLD should include the study of metagenomic and metabolomic profiles of the gut microbiome, both to identify subgroups of patients and to plan a rational and targeted administration of probiotic strains.
1. Park JS, Seo JH, Youn HS. Gut microbiota and clinical disease: obesity and nonalcoholic Fatty liver disease. Pediatr Gastroenterol Hepatol Nutr
2. Frasinariu OE, Ceccarelli S, Alisi A, et al. Gut-liver axis and fibrosis in nonalcoholic fatty liver disease: an input for novel therapies. Dig Liver Dis
3. Sabaté JM, Jouët P, Harnois F, et al. High prevalence of small intestinal bacterial overgrowth in patients with morbid obesity: a contributor to severe hepatic steatosis. Obes Surg
4. Del Chierico F, Nobili V, Vernocchi P, et al. Gut microbiota profiling of pediatric NAFLD and obese patients unveiled by an integrated meta-omics based approach. Hepatology
2016; [Epub ahead of print].
5. Li Z, Yang S, Lin H, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology
6. Famouri F, Shariat Z, Hashemipour M, et al. Effects of probiotics on non-alcoholic fatty liver disease in obese children and adolescents. J Pediatr Gastroenterol Nutr
7. Vajro P, Mandato C, Licenziati MR, et al. Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. J Pediatr Gastroenterol Nutr
8. Alisi A, Bedogni G, Baviera G, et al. Randomised clinical trial: the beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther