Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study.

BACKGROUND: The manipulation of gut microbiota via administration of probiotics has been proposed as a potential strategy for the treatment of non-alcoholic fatty liver disease (NAFLD). Hence, we performed a double-blind single center randomized placebo-controlled trial (RCT) to evaluate the efficacy of coadministration of probiotics with omega-3 vs. placebo in type-2 diabetic patients with NAFLD. METHODS: A total of 48 patients met the criteria for inclusion. They were randomly assigned to receive "Symbiter Omega" combination of probiotic biomass supplemented with flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5%) or placebo for 8-weeks. The primary main outcomes were the change in fatty liver index (FLI) and liver stiffness (LS) measured by Shear Wave Elastography (SWE). Secondary outcomes were the changes in transaminases level, serum lipids and cytokines levels. RESULTS: In probiotic-omega group, FLI significantly decreased from 83.53±2.60 to 76.26±2.96 (P<0.001) while no significant changes were observed in the placebo group (82.86±2.45 to 81.09±2.84; P=0.156). Changes of LS in both groups were insignificant. Analysis of secondary outcomes showed that the coadministration of probiotics with omega-3 lead to significant reduction of serum gamma-glutamyl transpeptidase, triglycerides, and total cholesterol. Chronic systemic inflammatory markers after intervention decrease significantly only in Symbiter Omega group: IL-1ß (P=0.029), TNF-α (P<0.001), IL-8 (P=0.029), IL-6 (P=0.003), and INF-γ (P=0.016). CONCLUSIONS: Coadministration of a live multi-strain probiotic mixture with omega-3 fatty acids once daily for 8 weeks to patients with NAFLD can reduce liver fat, improve serum lipids, metabolic profile, and reduce chronic systemic inflammatory state.

Effect of alive probiotic on insulin resistance in type 2 diabetes patients: Randomized clinical trial.

BACKGROUND: Probiotics have beneficial effect on obesity related disorders in animal models. Despite a large number of animal data, randomized placebo-controlled trials (RCT) concluded that probiotics have a moderate effect on glycemic control-related parameters. However, effect of probiotics on insulin resistance are inconsistent. AIM: In a double-blind single center RCT, effect of alive multistrain probiotic vs. placebo on insulin resistance in type 2 diabetes patient were assessed. METHODS: A total of 53 patients met the criteria for inclusion. They were randomly assigned to receive multiprobiotic "Symbiter" (concentrated biomass of 14 probiotic bacteria genera Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium) or placebo for 8-weeks administered as a sachet formulation. The primary main outcome was the change HOMA-IR (homeostasis model assessment-estimated insulin resistance) which calculated using Matthews et al.'s equation. Secondary outcomes were the changes in glycemic control-related parameters, anthropomorphic variables and cytokines. RESULTS: Supplementation with alive multiprobiotic for 8 weeks was associated with significant reduction of HOMA-IR from 6.85 ±â€¯0.76 to 5.13 ±â€¯0.49 (p = 0.047), but remained static in the placebo group. With respect to our secondary outcomes, HbA1c insignificant decreased by 0.09% (p = 0.383) and 0.24% (p = 0.068) respectively in placebo and probiotics groups. However, in probiotic responders (n = 22, patient with decrease in HOMA-IR) after supplementation a significant reduction in HbA1c by 0.39% (p = 0.022) as compared to non-responders was observed. In addition, from markers of chronic systemic inflammatory state only TNF-α and IL-1ß changes significantly after treatment with probiotics. CONCLUSION: Probiotic therapies modestly improved insulin resistance in patients with type 2 diabetes.

A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial.

BACKGROUND: Probiotics have a beneficial effect on nonalcoholic fatty liver disease (NAFLD) in animal models. Randomized placebo-controlled trials (RCTs) in NAFLD are still lacking in humans despite a large number of data from animal research. AIM: We performed a double-blind single center RCT of live multi-strain probiotic vs. placebo in type 2 diabetes patients with NAFLD. METHODS: A total of 58 patients met the criteria for inclusion. They were randomly assigned to receive the multi-probiotic "Symbiter" (concentrated biomass of 14 probiotic bacteria genera Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium) or placebo for 8-weeks administered as a sachet formulation in double-blind treatment. The primary main outcomes were the changes in fatty liver index (FLI) and liver stiffness (LS) measured by Shear Wave Elastography (SWE). Secondary outcomes were the changes in aminotransferase activity, serum lipids and cytokines (TNF-α, IL-1ß, IL-6, IL-8, and IFN-γ) levels. Analysis of covariance was used to assess the difference between groups. RESULTS: In the probiotic group, FLI significantly decreased from 84.33+/-2.23 to 78.73+/-2.58 (p<0.001) but it did not change in the placebo group (82.57+/-2.45 to 81.6 +/-2.36; p=0.367). In both groups a slight but not significant reduction of LS measured by SWE was detected. Analysis of the secondary outcomes showed that probiotics reduced the level of serum AST and GGT. Among the markers of chronic systemic inflammatory state, only TNF-α and IL-6 levels changed significantly after the treatment with the probiotic. CONCLUSION: The probiotic "Symbiter" reduces liver fat, aminotransferase activity, and the TNF-α and IL-6 levels in NAFLD patients. Modulation of the gut microbiota might represent a new therapy for NAFLD, which should be tested in larger studies.

Comparative experimental investigation on the efficacy of mono- and multiprobiotic strains in non-alcoholic fatty liver disease prevention.

BACKGROUND: To investigate the efficacy of different probiotic strains, their combinations and forms (alive or lyophilized) in nonalcoholic fatty liver disease (NAFLD) prevention. METHODS: In this study, 70 rats have been used divided into 7 groups of 10 animals in each: I - intact rats, II-VII - rats with monosodium glutamate (MSG)-induced NAFLD. Rats with NAFLD were untreated (group II, MSG-obesity group) and treated with probiotics (groups III-VII). In order to develop NAFLD, newborn rats of groups II-VII were injected with a solution of monosodium glutamate (MSG) (4 mg/g) subcutaneously (s.c.) at 2nd,4th, 6th, 8th,10th postnatal day. The groups III-V received lyophilized monoprobiotics B. animalis VKL, B. animalis VKB, L.casei IMVB-7280, respectively. The group VI received 2.5 ml/kg of an aqueous solution of a mixture of the three probiotic strains (2:1:1 Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, Bifidobacterium animalis VKB) at a dose of 50 mg/kg (5 × 10(9) CFU/kg) (g) (intragastrically). The group VII was treated with multiprobiotic "Symbiter" containing biomass of 14 alive probiotic strains (Lactobacillus + Lactococcus (6 × 10(10) CFU/g), Bifidobacterium (1 × 10(10)/g), Propionibacterium (3 × 10(10)/g), Acetobacter (1 × 10(6)/g)) at a dose of 140 mg/kg (1.4 × 10(10) CFU/kg). The treatment with probiotics was started at the age of 1 month. There were 3 courses of treatment, each included 2-week administration and 2-week break. All parameters were measured in 4-month aged rats. RESULTS: Introduction of MSG during the neonatal period leads to the NAFLD development in the 4-months old rats. For steatosis degree there was no significant difference between MSG-obesity group and lyophilized monocomponent probiotics groups (III-V). The highest manifestation of steatosis was observed for B. animalis VKL group (2.0 ± 0.25) as compared to B. animalis VKB (1.70 ± 0.21) and L. casei IMVB-7280 (1.80 ± 0.20). The steatosis score changes between all monoprobiotics groups (III-V) were insignificant. Administration from birth of both alive (VII) and lyophilized (VI) probiotic mixture lead to a significant decrease by 69.5 % (p < 0.001) and 43.5 % (p < 0.025) of steatosis score respectively as compared to the MSG-obesity group (2.3 ± 0.21 %). For both alive and lyophilized probiotic mixtures, reduction of lobular inflammation was observed. These histological data were confirmed by the significant decrease of total lipids and triglycerides content in the liver approximately by 22-25 % in groups treated with probiotic mixtures (VI, VII) compared to the MSG-obesity group. CONCLUSION: We established failure of NAFLD prevention with lyophilized monoprobiotic strains and the efficacy of probiotic mixture with the preference of alive probiotic strains.

Diagnostic accuracy of acyl-ghrelin and it association with non-alcoholic fatty liver disease in type 2 diabetic patients.

BACKGROUND: Ghrelin is a hormone produced mainly by the cells lining the fundus of the stomach, which is involved in regulation of lipid and glucose metabolism. Two major forms of ghrelin can be found in circulation: an acylated form, and non-acylated form. Serum acyl-ghrelin (AG) concentration is significantly increased in patients with visceral obesity and insulin resistance. This study was conducted to evaluate changes in serum AG levels, its diagnostic accuracy and association with NAFLD in patients with type two diabetes (T2D). METHODS: In this cross-sectional study, 91 T2D patients, age of 40-80 years, were included. All patients were divided into 3 groups. The control group included 28 T2D patients without NAFLD. The main group included 63 T2D patients with NAFLD, which was divided in 2 subgroups depending on transaminase levels: normal (n = 37) and elevated (n = 26) transaminases group. To assess the diagnostic accuracy of AG for NAFLD we used ROC-analysis. RESULTS: We observed 1.5 (p = 0.016) and 2.5 (p < 0.001) fold increasing of serum AG levels in patients with NAFLD and normal or elevated transaminases compared to control groups. In multivariate logistic regression analysis high AG level was an independent, from transaminases activity, triglycerides (OR 1.791; 95 % CI 1.162-2.759; p = 0.008) and degree of IR (OR 1.599; 95 % CI 1.019-2.508; p = 0.044) predictor that associated with NAFLD. When serum AG used as non-invasive marker for NAFLD detection AUROC was 0.835 (95 % CI 0.752-0.918, p < 0.001). The cut-off value was >0.52 ng/ml, with sensitivity, specificity, PPV and NPV - 60.3 %, 92.8 %, 95.0 %, 50.9 % respectively. For distinguishing patients with NAFLD and elevated transaminases from patients with NAFLD and normal values AG was less effective. CONCLUSIONS: Our study has demonstrated that elevated AG level were associated with NAFLD. Patients with elevated transaminases had significantly higher AG levels. An increase of AG over 0.52 ng/ml can be used as a diagnostic marker for NAFLD detection in patients with T2D.