Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease

Scorletti, Eleonora; Afolabi, Paul R.; Miles, Elizabeth A.; Smith, Debbie E.; Almehmadi, Amal; Alshathry, Albandri; Childs, Caroline E.; Fabbro, Stefania Del; Bilson, Josh; Moyses, Helen; Clough, Geraldine F.; Sethi, J.; Patel, Janisha; Wright, Mark; Breen, David J.; Peebles, Charles; Darekar, Angela; Aspinall, Richard J; Fowell, Andrew; Dowman, Joanna; Nobili, Valério; Targher, Giovanni; Delzenne, Nathalie M.; Bindels, Laure B.; Calder, Philip C.; Byrne, Christopher D.

doi:10.1053/j.gastro.2020.01.031

Cited by 152 publications

(117 citation statements)

References 72 publications

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“…In NASH patients, a synbiotic composed of Bifidobacterium longum and FOS reduced AST, cholesterol, CRP, TNF-alpha, HOMA-IR, serum endotoxin, steatosis and NASH activity index [ 105 ]. A phase II clinical trial investigated the effect of a synbiotic composed of FOS and Bifidobacterium animalis subspecies lactis BB-12 in 104 NAFLD patients [ 106 ]. The synbiotic increased faecal Bifidobacterium and Faecalibacterium and decreased Oscillibacter and Alistipes species, whereas placebo did not cause these changes.…”

Section: Modulation Of Gut Microbiota and Its Metabolitesmentioning

confidence: 99%

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

Chen¹,

Vitetta

2020

IJMS

183

137

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Gut microbiota dysregulation plays a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) through its metabolites. Therefore, the restoration of the gut microbiota and supplementation with commensal bacterial metabolites can be of therapeutic benefit against the disease. In this review, we summarize the roles of various bacterial metabolites in the pathogenesis of NAFLD and their therapeutic implications. The gut microbiota dysregulation is a feature of NAFLD, and the signatures of gut microbiota are associated with the severity of the disease through altered bacterial metabolites. Disturbance of bile acid metabolism leads to underactivation of bile acid receptors FXR and TGR5, causal for decreased energy expenditure, increased lipogenesis, increased bile acid synthesis and increased macrophage activity. Decreased production of butyrate results in increased intestinal inflammation, increased gut permeability, endotoxemia and systemic inflammation. Dysregulation of amino acids and choline also contributes to lipid accumulation and to a chronic inflammatory status. In some NAFLD patients, overproduction of ethanol produced by bacteria is responsible for hepatic inflammation. Many approaches including probiotics, prebiotics, synbiotics, faecal microbiome transplantation and a fasting-mimicking diet have been applied to restore the gut microbiota for the improvement of NAFLD.

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Section: Modulation Of Gut Microbiota and Its Metabolitesmentioning

confidence: 99%

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

Chen¹,

Vitetta

2020

IJMS

183

137

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“…Clinical data on such diets in NAFLD patients are currently lacking. Recently, 1-year administration of a symbiotic combination (one probiotic and one prebiotic) was shown to change the fecal microbiome but had no effect on liver fat or fibrosis compared to placebo in NAFLD patients [166].…”

Section: Dietary Interventionsmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

Fougerat

Montagner

Loiseau

et al. 2020

Cells

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Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis is the initial stage of the disease, which is characterized by lipid accumulation in hepatocytes, which can progress to non-alcoholic steatohepatitis (NASH) with inflammation and various levels of fibrosis that further increase the risk of developing cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is influenced by interactions between genetic and environmental factors and involves several biological processes in multiple organs. No effective therapy is currently available for the treatment of NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate many functions that are disturbed in NAFLD, including glucose and lipid metabolism, as well as inflammation. Thus, they represent relevant clinical targets for NAFLD. In this review, we describe the determinants and mechanisms underlying the pathogenesis of NAFLD, its progression and complications, as well as the current therapeutic strategies that are employed. We also focus on the complementary and distinct roles of PPAR isotypes in many biological processes and on the effects of first-generation PPAR agonists. Finally, we review novel and safe PPAR agonists with improved efficacy and their potential use in the treatment of NAFLD.

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“…Four RCTs investigated stand-alone probiotics, probiotics combined with prebiotics (synbiotics), and medicinal mushrooms, of which two in NASH patients [ 34 , 35 ], one in NAFLD patients [ 36 ] and one in patients with elevated liver enzymes [ 37 ]. Ferolla et al [ 34 ] compared the effects of Lactobacillus reuteri (0.1 × 10 9 CFU/d) combined with dietary fiber (4000 mg) vs. lifestyle recommendations alone over 13 weeks in 50 NASH patients using MRI-PDFF.…”

Section: Resultsmentioning

confidence: 99%

Efficacy of Dietary Supplements to Reduce Liver Fat

et al. 2020

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Liver fat accumulation is an important pathophysiological feature of non-alcoholic fatty liver disease that may be modulated by dietary supplements (DS). A systematic search of the literature was conducted for randomized controlled trials (RCTs) pertaining to the effect of a DS on liver fat as assessed using quantitative tomographic imaging in human adults. Where feasible, data were pooled, and meta-analyses conducted using random-effect model. Quality assessment was done according the Cochrane Collaboration’s tool for assessing risk of bias. Twenty RCTs, involving 1171 overweight and obese adults, of which 36% were females, with or without comorbidities, were included. Only RCTs assessing omega-3 fatty acids (n = 4) and resveratrol (n = 4) qualified for meta-analysis. Results did neither favor omega-3 (effect size −1.17; weighted mean difference (WMD) (95% confidence interval (CI)) −3.62, 1.28; p < 0.001) nor resveratrol supplementation (0.18; 95% CI −1.08, 1.43; p = 0.27). The findings of the qualitatively summarized RCTs suggested that catechins (n = 1), Lactobacillus reuteri (n = 1), and carnitine (n = 1) may reduce liver fat. All other DS did not show any influence. The current evidence is scarce, of limited quality and does not support DS use to reduce liver fat. Further well-designed trials are warranted.

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Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease

Abstract: Chr. Hansen had no input into any aspect of study design or conduct of the trial. Furthermore, Chr. Hansen will have no input into data analysis or subsequent reporting of the trial results. PCC has received consulting fees from Chr. Hansen, but not in relation to this trial.

Cited by 152 publications

References 72 publications

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

Efficacy of Dietary Supplements to Reduce Liver Fat

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