The worldwide prevalence of obesity more than doubled between 1980 and 2014. The obesity pandemic is tightly linked to an increase in energy availability, sedentariness and greater control of ambient temperature that have paralleled the socioeconomic development of the past decades. The most frequent cause which leads to the obesity development is a dysbalance between energy intake and energy expenditure. The gut microbiota as an environmental factor which influence whole-body metabolism by affecting energy balance but also inflammation and gut barrier function, integrate peripheral and central food intake regulatory signals and thereby increase body weight. Probiotics have physiologic functions that contribute to the health of gut microbiota, can affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community.

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 multiprobiotic “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-1β, 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.

Allergic diseases have been a global problem over the past few decades. The effect of allergic diseases on healthcare systems and society is generally remarkable and is considered as one of the most common causes of chronic and hospitalized disease. The functional ability of probiotics to modulate the innate/acquired immune system leads to the initiation of mucosal/systemic immune responses. Gut microbiota plays a beneficial role in food digestion, development of the immune system, control/growth of the intestinal epithelial cells and their differentiation. Prescribing probiotics causes a significant change in the intestinal microflora and modulates cytokine secretion, including networks of genes, TLRs, signaling molecules and increased intestinal IgA responses. The modulation of the Th1/Th2 balance is done by probiotics, which suppress Th2 responses with shifts to Th1 and thereby prevent allergies. In general, probiotics are associated with a decrease in inflammation by increasing butyrate production and induction of tolerance with an increase in the ratio of cytokines such as IL-4, IL-10/IFN-γ, Treg/TGF-β, reducing serum eosinophil levels and the expression of metalloproteinase-9 which contribute to the improvement of the allergic disease's symptoms. Finally, it can be said that the therapeutic approach to immunotherapy and the reduction of the risk of side effects in the treatment of allergic diseases is the first priority of treatment and the final approach that completes the first priority in maintaining the condition and sustainability of the tolerance along with the recovery of the individual.

Overweight and obesity increase the risk for a number of diseases, namely, cardiovascular diseases, type 2 diabetes, dyslipidemia, premature death, non-alcoholic fatty liver disease as well as different types of cancer. Approximately 1.7 billion people in the world suffer from being overweight, most notably in developed countries. Current research efforts have focused on host and environmental factors that may affect energy balance. It was hypothesized that a microbiota profile specific to an obese host with increased energy-yielding behavior may exist. Consequently, the gut microbiota is becoming of significant research interest in relation to obesity in an attempt to better understand the aetiology of obesity and to develop new methods of its prevention and treatment. Alteration of microbiota composition may stimulate development of obesity and other metabolic diseases via several mechanisms: increasing gut permeability with subsequent metabolic inflammation; increasing energy harvest from the diet; impairing short-chain fatty acids synthesis; and altering bile acids metabolism and FXR/TGR5 signaling. Prebiotics and probiotics have physiologic functions that contribute to the health of gut microbiota, maintenance of a healthy body weight and control of factors associated with obesity through their effects on mechanisms that control food intake, body weight, gut microbiota and inflammatory processes.

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. 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. 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-1β (P=0.029), TNF-α (P<0.001), IL-8 (P=0.029), IL-6 (P=0.003), and INF-γ (P=0.016). 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.