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Systematic review on intervention with prebiotics/probiotics in patients with obesity-related nonalcoholic fatty liver disease Giovanni Tarantino*,1,2 & Carmine Finelli3 Abstract Background: The gut microbiota is modulated by metabolic derangements, such as nutrition overload and obesity. Aim: The aim of this systematic review is to summarize the role of these gut modifiers in nonalcoholic fatty liver disease (NAFLD) and obesity. Methods: A systematic search of MEDLINE (from 1946), PubMed (from 1946) and EMBASE (from 1949) databases through May 2014 was carried out to identify relevant articles. The search terms were ‘probiotic’ AND ‘NAFLD’, ‘prebiotic’ AND ‘NAFLD,’ ‘antibiotic’ AND ‘NAFLD,’ ‘probiotics’ AND ‘obesity,’ ‘prebiotic’ AND ‘obesity’ or ‘antibiotic’ AND ‘obesity’; these terms were searched as text word in ‘clinical trials’ and as exploded medical subject headings where possible. Results: The evidence in the literature is scant, due to the scarcity of appropriately powered, randomized, controlled clinical trials, involving various centers and population of different origin. Conclusion: Although probiotics and prebiotics have been proposed in the treatment and prevention of patients with obesity-related NAFLD, their therapeutic use is not supported by high-quality clinical studies. A complex community of microorganisms inhabits the gastrointestinal tract all through its length. The gut is the main site of microbial colonization and, usually, the indigenous microbiota are believed to comprise several bacterial species. Although the majority of the intestinal bacteria are constituted by the Bacteroidetes and Firmicutes phyla, Proteobacteria, Actinobacteria, Fusobacteria, Verrucomicrobia and Cyanobacteria phyla are also found in the human intestine. Recent molecular studies have confirmed the view of microbial diversity within the gut [1] . The gut microbiota plays an important role in both human health and disease [1,2] . Various factors, such as hygienic habits, actual or past infections followed by antibiotic therapy, as well as age and diet, affect the gut flora. Recent research lends credence to the hypothesis that gut microbiota is a fine modulator of energy homeostasis and ectopic fat deposition, the implications of which are clearly present in dysmetabolic illnesses [3,4] . Obese people have been recognized to harbor lower Bacteroidetes and more Firmicutes in their distal gut when compared with lean controls, and this gut flora modification was reverted after diet-induced weight loss [5] . Other factors that may contribute to the development of the intestinal microflora include initial colonization after birth, driven by the presence of selective nutrients in the mother’s milk; host genetic factors that influence the secretion of substances that facilitate selection for specific bacteria; immune surveillance that favors the growth of some groups of bacteria; and random chance resulting in a colonization cascade. Elevated activity levels might change other aspects of intestinal physiology and, in this manner, the conditions for microbial growth [6–9] .

Keywords 

• gut microbiota • nonalcoholic fatty liver disease • nonalcoholic steatohepatitis • obesity • prebiotics • probiotics

Department of Clinical Medicine & Surgery, Federico II University Medical School of Naples, Naples, Italy Centro Ricerche Oncologiche di Mercogliano, Istituto Nazionale Per Lo Studio E La Cura Dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Mercogliano (Av), Italy 3 Center of Obesity & Eating Disorders, Stella Maris Mediterraneum Foundation, Chiaromonte, Potenza, Italy *Author for correspondence: [email protected] 1 2

10.2217/FMB.15.13 © 2015 Future Medicine Ltd

Future Microbiol. (2015) 10(5), 889–902

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Reduction in serum AST levels (p = 0.008)

28 Spain 2011 Double-blind randomized clinical trial Aller et al. /Eur. Rev. Med. Pharmacol. Sci./ 1.093/46-32

10 Randomized

2013 China

Future Microbiol. (2015) 10(5)

ALT: Alanine amino transferase; AST: Aspartate aminotransferase; GT: Glutamine transferase; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis .

– Improved liver aminotransferases (ALT: 67.7 +/- 25.1 vs. 60.4 +/- 30.4 UI/l; p < 0.05), (AST: 41.3 +/- 15.5 vs 35.6 +/- 10.4 UI/l; p < 0.05) and gammaglutamine transferase levels (gammaGT: 118.2 +/- 63.1 vs 107.7 +/- 60.8 UI/l; p < 0.05) decreased

– 6 months Probiotic (Lactobacillus plantarum, Lactobacillus deslbrueckii, Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium bifidum) NAFLD Probiotic (Lactobacillus 500 3 months (diagnosed bulgaricus and million by liver Streptococcus biopsy) thermophilus)

Intrahepatic triglyceride content decreased (22.6 ± 8.2% to 14.9 ± 7.0%; p = 0.034)

[26]

[23]

– – 30 days – Multiprobiotic

Type 2 diabetes and NAFLD Histologyproven NASH 45 Observational 2013 Ukraine

Mykhal’chyshyn et al. Lik. Sprava./ n.c./0/0 Wong et al. /Ann. Hepatol./1.671/ 16-12

Country Patients Medical total (n) condition and disease Year Author/journal/ Study design impact factor/ number of citations (Google scholar-Scopus)

Table 1. Probiotics and nonalcoholic fatty liver disease.

Type of treatment

Dose (CFU per day)

Treatment Primary outcome, weight loss duration (kg)

Secondary outcome (

probiotics in patients with obesity-related nonalcoholic fatty liver disease.

The gut microbiota is modulated by metabolic derangements, such as nutrition overload and obesity...
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