Randomized, Double-blind, Placebo-controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease

Ahn, Sang Bong; Jun, Dae Won; Kang, Bo Kyeong; Lim, Jong Hyun; Lim, Sanghyun; Chung, Myung Jun

doi:10.1038/s41598-019-42059-3

Cited by 145 publications

(110 citation statements)

References 29 publications

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“…In another study, reduction of triglycerides was more significant in the probiotic treatment group than in the placebo group. However, the changes in the percentage of intrahepatic fat fraction and triglyceride levels were not different between placebo and control groups after adjusting for changes in body weight [56].…”

Section: Probiotics/prebioticsmentioning

confidence: 76%

Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy

Tarantino

Citro

Capone

2019

JCM

114

110

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Focusing on previously published mechanisms of non-alcoholic fatty liver disease (NAFLD), their uncertainty does not always permit a clear elucidation of the grassroot alterations that are at the basis of the wide-spread illness, and thus curing it is still a challenge. There is somehow exceptional progress, but many controversies persist in NAFLD research and clinical investigation. It is likely that hidden mechanisms will be brought to light in the near future. Hereby, the authors present, with some criticism, classical mechanisms that stand at the basis of NAFLD, and consider contextually different emerging processes. Without ascertaining these complex interactions, investigators have a long way left ahead before finding an effective therapy for NAFLD beyond diet and exercise. few are conclusively accepted by experts. We try to provide evidence of the complexity, and for some aspects the contradictions, of the main lines of basic and clinical research addressing this topic. The Role of Reactive Oxygen Species (ROS) OverproductionMalnutrition splits in two directions; undernutrition and overnutrition; both of them leading to severe health complications: Famine and overweight/obesity are the result of calorie deficit or excess, and both of them are major health problems. Constantly eating excess calories leads body fat stores to expand. One of the most active and productive hypotheses about the mechanisms inducing or worsening obesity and consequently NAFLD is the over-production of reactive oxygen species (ROS). Oxidative stress accompanying obesity is reckoned to be a key factor in the development of insulin resistance (IR), [4]. In fact, obese mice treated with NADPH oxidase inhibitors (reducing ROS) have clearly demonstrated the involvement of ROS in the genesis of IR, hepatic steatosis, and T2DM [5]. Mitochondria are clearly considered to be main contributors to oxidative stress in obesity induced by chronic over-nutrition, with subsequent reduced insulin sensitivity or IR [6]. The trigger that causes the oxidative stress in obesity is the energy surplus that eventually generates reducing equivalents. These exceed the rate of ATP utilization, giving space to the over-production of O 2 , and consequently reducing the redox-buffering capacity [7]. The aforementioned pathway has been fully highlighted in mice, characterized by deletion of manganese superoxide dismutase at the adipocyte level through enhanced mitochondrial biogenesis, mediated by uncoupling protein 1 [8].

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Section: Probiotics/prebioticsmentioning

confidence: 76%

Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy

Tarantino

Citro

Capone

2019

JCM

114

110

View full text Add to dashboard Cite

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“…Evidence from a randomized, double-blind, placebocontrolled study demonstrated that administration of a multispecies probiotic mixture reduces the intrahepatic fat and body weight in obese NAFLD patients (Ahn et al 2019). Animal studies have also shown that co-administration with cholesterol-lowering probiotics (two strains) and anthraquinone from Cassia obtusifolia L. has potential therapeutic effects for NAFLD (Mei et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Probiotic Bifidobacterium lactis V9 attenuates hepatic steatosis and inflammation in rats with non-alcoholic fatty liver disease

et al. 2020

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Both steatosis and inflammation are key pathological events in the progression of non-alcoholic fatty liver disease (NAFLD). Probiotics are beneficial for the prevention and treatment of NAFLD. Bifidobacterium animalis subsp. lactis V9 (V9) is a newly isolated strain with favorable probiotic properties. The study aims to evaluate the effects and mechanisms of V9 on the hepatic steatosis and inflammatory responses in a rat model of NAFLD induced by high-fat diets (HFD). Our results showed that administration of V9 significantly attenuated the HFD-induced increases in alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, resulting in alleviated hepatic steatosis. V9 supplementation reduced the accumulation of hepatic triglyceride and free fatty acid,while increasing the levels of glycogen. Serum levels of glucose were also decreased in HFD rats administrated with V9. Meanwhile, the transcription of SREBP-1c and FAS was reduced, and the hepatic expression of phosphorylated-AMPK and PPAR-α was restored after V9 administration. V9 suppressed the production of inflammatory cytokines (e.g. IL-6, IL-1β, and TNF-α) in HFD-fed rats. The anti-inflammatory effects of V9 was found to be associated with the inhibition of hepatic expression of TLR4, TLR9, NLRP3, and ASC mRNA. Furthermore, the activation of ERK, JNK, AKT and NF-κB were suppressed by V9 treatment. These results indicate that Bifidobacterium lactis V9 improves NAFLD by regulating de novo lipid synthesis and suppressing inflammation through AMPK and TLR-NF-κB pathways, respectively.

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“…Especially findings on Ruminococcus are rather controversial, as two other studies showed an increase in its presence in NAFLD suggesting that further studies are needed (34, 35). Only very few interventional studies in human NAFLD are so far available (27). This study assessed the effects of a probiotic treatment consisting of Lactobacillus acidophilus, L. rhamnosus, L. paracasei, Pediococcus pentosaceus, Bifidobacterium lactis , and B. breve on visceral and intrahepatic fat in NAFLD.…”

Section: Bacterial Dysbiosis In Nafldmentioning

confidence: 99%

“…TMA is produced by bacteria out of dietary compounds, in the liver it is further metabolized to TMAO, which leads to an increased risk for cardiovascular events (D) . Recently published data (27) show that a cocktail of prebiotics can reduce the intrahepatic fat content in steatotic patients (E) .…”

Section: Introductionmentioning

confidence: 99%

Gut Dysfunction and Non-alcoholic Fatty Liver Disease

et al. 2019

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Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the leading liver diseases worldwide. NAFLD is characterized by hepatic steatosis and may progress to an inflammatory condition termed non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. It became evident in the last years that NAFLD pathophysiology is complex and involves diverse immunological and metabolic pathways. An association between intestinal signals (e.g., derived from the gut microbiota) and the development of obesity and its metabolic consequences such as NAFLD are increasingly recognized. Pre-clinical studies have shown that germ-free mice are protected against obesity and hepatic steatosis. Several human studies from the past years have demonstrated that NAFLD contains a disease-specific gut microbiome signature. Controlled studies propose that certain bacteria with rather pro-inflammatory features such as Proteobacteria or Escherichia coli are dominantly present in these patients. In contrast, rather protective bacteria such as Faecalibacterium prausnitzii are decreased in NAFLD patients. Furthermore, various bacterial metabolites and microbiota-generated secondary bile acids are involved in NAFLD-associated metabolic dysfunction. Although these findings are exciting, research currently lack evidence that interference at the level of the gut microbiome is beneficial for these diseases. Further preclinical and clinical studies are needed to advance this aspect of NAFLD research and to support the notion that the intestinal microbiota is indeed of major relevance in this disorder.

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Randomized, Double-blind, Placebo-controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease

Cited by 145 publications

References 29 publications

Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy

Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy

Probiotic Bifidobacterium lactis V9 attenuates hepatic steatosis and inflammation in rats with non-alcoholic fatty liver disease

Gut Dysfunction and Non-alcoholic Fatty Liver Disease

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