title: Effect of symbiotic supplementation on glycemic control, lipid profiles and microalbuminuria in patients with non-obese type 2 diabetes: a randomized, double-blind, clinical trial Bifidobacterium longum with Fructo-Oligosaccharides in Patients with Non Alcoholic Steatohepatitis Consumption of Synbiotic Bread Decreases Triacylglycerol and VLDL Levels While Increasing HDL Levels in Serum from Patients with Type-2 Diabetes Effect of the consumption of a new symbiotic shake on glycemia and cholesterol levels in elderly people with type 2 diabetes mellitus Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Do symbiotic and Vitamin E supplementation have favorite effects in nonalcoholic fatty liver disease? A randomized, double-blind, placebo-controlled trial Effect of Lactobacillus rhamnosus CGMCC1.3724 supplementation on weight loss and maintenance in obese men and women. Influence of a combination of Lactobacillus acidophilus NCFM and lactitol on healthy elderly: intestinal and immune parameters. Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: a pilot, randomised, double-blind, placebo-controlled, clinical trial. Combined effects of synbiotic and sitagliptin versus sitagliptin alone in patients with nonalcoholic fatty liver disease Daily Consumption of Synbiotic Yogurt Decreases Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial.
abstract: Background The prevalent raise of type 2 diabetes ( T2D ) around the globe , are creating higher risk for cardiovascular diseases ( CVDs ) and increasing strain on each country ’s health care budget in the world . Microalbuminuria has appeared as a key parameter in diabetic patients . Microalbuminuria is also related to increased cardiovascular morbidity in people who are non-obese diabetic . Some studies have suggested that consumption of symbiotic foods might help improve the metabolic profile , inflammatory factors and biomarkers of oxidative stress . The aim of trial was to determine the effect of symbiotic supplementation on glycemic control , lipid profiles and microalbuminuria in non-obese T2D . Methods In this r and omized , double-blind , clinical ly controlled trial , 70 patients with T2D ( 28 females , 42 males ) were r and omly divided into two groups ( n = 35 for each group ) . The symbiotic group ( SG ) consumed 500 mg/d of symbiotic supplementations containing probiotics ( Lactobacillus family , Bifidobacterium family , Streptococus thermophilus ) , Prebiotics ( Fructo oligosaccharide ) and B group vitamins ( 1 mg ) , lactose ( 0.5 mg ) , malt-dextrin , magnesium saturate and the placebo group ( PG ) consumed capsules filled with row starch and also B group vitamins ( 1 mg ) , lactose ( 0.5 mg ) , malt-dextrin , magnesium saturate for 9 weeks . Fasting blood glucose ( FBG ) , hemoglobin A1c ( HbA1c ) , blood lipid profiles , 24-h dietary recalls , and anthropometric measurements were measured at the baseline and at the end of trial . SPSS software , version 16 was used to test the data and the results were expressed as mean ± st and ard deviation . Paired sample s T-Test were used to compare continuous variables within groups . Comparison between different groups was performed through two independent sample s T-Test . In the absence of normal distribution , the comparison between the groups was made using non-parametric Wilcoxon on signed ranks and Mann – Whitney tests . P values < 0.05 was considered significant . Results Symbiotic supplementation decreased significantly , FBG ( P = 0.05 ) and HbA1c ( P < 0.01 ) . There were no significant differences in lipid profiles within and between the groups at the end of study ( P > 0.05 ) . Microalbuminuria ( P < 0.05 ) and HbA1c ( P < 0.05 ) are increased significantly in PG at the end of the study . Furthermore , the mean changes of microalbuminuria and HbA1c experienced significant between the two groups . There was significant reduction in urea between two groups from baseline ( P = 0.051 ) . No significant changes in baseline were shown in creatinine among the two groups or within either groups ( P > 0.05 ) . Conclusion The consumption of 500 mg/d symbiotic supplementation for 9 weeks could improve the HbA1c , BMI and Microalbuminuria in T2D . Although , No effect has been indicated on FBS , lipid profiles , urea and creatinine . Trial Registration The trial has been registered in the Iranian Registry of Clinical Trials I RCT 2015072223284N1 , identifier . Registered 21 May 2016 “ retrospectively registered ” Background Increased exposure to intestinal bacterial products may contribute to the pathogenesis of non alcoholic steatohepatitis ( NASH ) . Bifidobacteria are predominant bacterial species in the human gut microbiota and have been considered to exert a beneficial effect on human health by maintaining the equilibrium of the resident microbiota . Aims To evaluate the effects of Bifidobacterium longum with fructo-oligosaccharides ( Fos ) in the treatment of NASH . Methods A total of 66 patients were r and omly and equally divided into two groups receiving Bifidobacterium longum with Fos and lifestyle modification ( i.e. , diet and exercise ) versus lifestyle modification alone . The following variables were assessed at −4 ( beginning of the dietary lead-in period ) , 0 ( r and omization ) , 6 , 12 , 18 , and 24 weeks : aspartate transaminase ( AST ) , alanine transaminase ( ALT ) , bilirubin , albumin , total cholesterol , high-density lipoprotein ( HDL ) cholesterol , low-density lipoprotein ( LDL ) cholesterol , triglycerides , fasting plasma glucose , insulin , C-peptide , C-reactive protein ( CRP ) , tumor necrosis factor (TNF)-α , homeostasis model assessment of insulin resistance ( HOMA-IR ) , and serum endotoxins . Liver biopsies were performed at entry and repeated after 24 weeks of treatment . Results At the end of study period , we observed that the Bifidobacterium longum with Fos and lifestyle modification group versus the lifestyle modification alone group showed significant differences in the AST −69.6 versus −45.9 IU/mL ( P < 0.05 ) , LDL cholesterol −0.84 versus −0.18 mmol/L ( P < 0.001 ) , CRP −2.9 versus −0.7 mg/L ( P < 0.05 ) , TNF-α −0.45 versus −0.12 ng/mL ( P < 0.001 ) , HOMA-IR −1.1 versus −0.6 ( P < 0.001 ) , serum endotoxin −45.2 versus −30.6 pg/mL ( P < 0.001 ) , steatosis ( P < 0.05 ) , and the NASH activity index ( P < 0.05 ) . Conclusions Bifidobacterium longum with Fos and lifestyle modification , when compared to lifestyle modification alone , significantly reduces TNF-α , CRP , serum AST levels , HOMA-IR , serum endotoxin , steatosis , and the NASH activity index To our knowledge , no reports are available indicating the favorable effects of synbiotic bread consumption on blood lipid profiles among patients with type 2 diabetes mellitus ( T2DM ) . This study was conducted to evaluate the effects of the daily consumption of synbiotic bread on blood lipid profiles of patients with T2DM . This r and omized double-blinded controlled clinical trial was performed with 78 diabetic patients , aged 35–70 years . After a 2-week run-in period , subjects were r and omly assigned to consume either synbiotic ( n = 26 ) , probiotic ( n = 26 ) or control bread ( n = 26 ) for 8 weeks . The synbiotic bread contained viable and heat-resistant probiotic Lactobacillus sporogenes ( 1 × 108 CFU ) and 0.07 g inulin ( HPX ) as prebiotic per 1 g. The probiotic bread contained L. sporogenes ( 1 × 108 CFU ) per 1 g. Patients were asked to consume the synbiotic , probiotic and control breads three times a day in a 40 g package for a total of 120 g/day . Biochemical measurements including blood lipid profiles were conducted before and after 8 weeks of intervention . Consumption of the synbiotic bread , compared to the probiotic and control breads , led to a significant decrease in serum TAG ( P = 0.005 ) , VLDL-C ( P = 0.005 ) , TC/HDL-C ( P = 0.002 ) and a significant increase in serum HDL-C levels ( P = 0.01 ) . No significant effect of synbiotic bread consumption on FPG , TC , LDL-C and non-HDL-C levels was seen compared to the probiotic and control breads ( P > 0.05 ) . Trial registry code : http://www.i rct .ir I RCT 201311215623N13 Background The consumption of foods containing probiotic and prebiotic ingredients is growing consistently every year , and in view of the limited number of studies investigating their effect in the elderly . Objective The objective of this study was to evaluate the effect of the consumption of a symbiotic shake containing Lactobacillus acidophilus , Bifidobacterium bifidum and fructooligosaccharides on glycemia and cholesterol levels in elderly people . Methods A r and omized , double-blind , placebo-controlled study was conducted on twenty volunteers ( ten for placebo group and ten for symbiotic group ) , aged 50 to 60 years . The criteria for inclusion in the study were : total cholesterol > 200 mg/dL ; triglycerides > 200 mg/dL and glycemia > 110 mg/dL. Over a total test period of 30 days , 10 individuals ( the symbiotic group ) consumed a daily dose of 200 mL of a symbiotic shake containing 108 UFC/mL Lactobacillus acidophilus , 108 UFC/mL Bifidobacterium bifidum and 2 g oligofructose , while 10 other volunteers ( the  placebo group ) drank daily the same amount of a shake that did not contain any symbiotic bacteria . Blood sample s were collected 15 days prior to the start of the experiment and at 10-day intervals after the beginning of the shake intake . The st and ard lipid profile ( total cholesterol , triglycerides and HDL cholesterol ) and glycemia , or blood sugar levels , were evaluated by an enzyme colorimetric assay . Results The results of the symbiotic group showed a non-significant reduction ( P > 0.05 ) in total cholesterol and triglycerides , a significant increase ( P < 0.05 ) in HDL cholesterol and a significant reduction ( P < 0.05 ) in fasting glycemia . No significant changes were observed in the placebo group . Conclusion The consumption of symbiotic shake result ed in a significant increase in HDL and a significant decrease of glycemia . Trial Registration Clinical Trials.gov : Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries ; it can progress to nonalcoholic steatohepatitis ( NASH ) , cirrhosis and hepatocarcinoma . The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients . In a r and omized , controlled clinical trial , involving 50 biopsy-proven NASH patients , we investigated the effects of synbiotic supplementation on metabolic parameters , hepatic steatosis , intestinal permeability , small intestinal bacterial overgrowth ( SIBO ) and lipopolysaccharide ( LPS ) serum levels . Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone . Before and after the intervention we assessed steatosis by magnetic resonance imaging , intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing .  NASH patients presented high gut permeability , but low prevalence of SIBO . After the intervention , only the synbiotic group presented a reduction in steatosis , lost weight , diminished BMI and waist circumference measurement . Synbiotic did not improve intestinal permeability or LPS levels . We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background : Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Oral administration of symbiotic and Vitamin E has been proposed as an effective treatment in NAFLD patients . This study was carried out to assess the effects of symbiotic and /or Vitamin E supplementation on liver enzymes , leptin , lipid profile , and some parameters of insulin resistance ( IR ) in NAFLD patients . Material s and Methods : We r and omly assigned sixty NAFLD adult patients to receive ( 1 ) symbiotic twice daily + Vitamin E-like placebo capsule ; ( 2 ) 400 IU/d Vitamin E + symbiotic-like placebo ; ( 3 ) symbiotic twice daily + 400 IU/d Vitamin E ; and ( 4 ) symbiotic-like placebo + Vitamin E-like placebo for 8 weeks . Results : Symbiotic plus Vitamin E supplementation led to a significant decrease in concentrations of liver transaminase ( P ≤ 0.05 ) . Mean difference of apolipoprotein A-1 was more significant in symbiotic group compared to control . However , mean difference of apolipoprotein B100/A-1 was only significant in symbiotic group compared to control . At the end of the study , significant differences in total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) were seen between the symbiotic plus Vitamin E and control groups ( P < 0.001 ) . Furthermore , intake of symbiotic plus Vitamin E supplements led to a significant decrease in concentrations of triglycerides ( TG ) after the intervention . Significant differences in leptin , fasting blood sugar ( FBS ) , and insulin levels were seen between the symbiotic plus Vitamin E and control groups at the end of the study ( P < 0.001 ) . In contrast , symbiotic and /or Vitamin E supplementation did not affect high-density lipoprotein cholesterol and homeostasis model assessment for IR levels . Conclusion : In our study , symbiotic plus Vitamin E supplementation was the most effective treatment in lowering liver enzymes , leptin , FBS , insulin , TG , TC , and LDL-C among NAFLD patients The present study investigated the impact of a Lactobacillus rhamnosus CGMCC1.3724 ( LPR ) supplementation on weight loss and maintenance in obese men and women over 24 weeks . In a double-blind , placebo-controlled , r and omised trial , each subject consumed two capsules per d of either a placebo or a LPR formulation ( 1.6 × 10(8 ) colony-forming units of LPR/capsule with oligofructose and inulin ) . Each group was su bmi tted to moderate energy restriction for the first 12 weeks followed by 12 weeks of weight maintenance . Body weight and composition were measured at baseline , at week 12 and at week 24 . The intention-to-treat analysis showed that after the first 12 weeks and after 24 weeks , mean weight loss was not significantly different between the LPR and placebo groups when all the subjects were considered . However , a significant treatment × sex interaction was observed . The mean weight loss in women in the LPR group was significantly higher than that in women in the placebo group ( P = 0.02 ) after the first 12 weeks , whereas it was similar in men in the two groups ( P= 0.53 ) . Women in the LPR group continued to lose body weight and fat mass during the weight-maintenance period , whereas opposite changes were observed in the placebo group . Changes in body weight and fat mass during the weight-maintenance period were similar in men in both the groups . LPR-induced  weight loss in women was associated not only with significant reductions in fat mass and circulating leptin concentrations but also with the relative abundance of bacteria of the Lachnospiraceae family in faeces . The present study shows that the Lactobacillus rhamnosus CGMCC1.3724 formulation helps obese women to achieve sustainable weight loss With increasing age , a number of physiological changes take place which are reflected in immune and bowel function . These changes may relate to the commonly assumed age-related changes in intestinal microbiota ; most noticeably a reduction in bifidobacteria . The current study aim ed at modifying the intestinal microbiota with a potential synbiotic on selected immune and microbiota markers . Healthy elderly subjects were r and omised to consume during 2 weeks either a placebo ( sucrose ) or a combination of lactitol and Lactobacillus acidophilus NCFM twice daily in a double-blind parallel trial . After the intervention , stool frequency was higher in the synbiotic group than in the placebo group and a significant increase in faecal L. acidophilus NCFM levels was observed in the synbiotic group , after baseline correction . In contrast to the generally held opinion , the study subjects had faecal Bifidobacterium levels that were similar to those reported in healthy young adults . These levels were , nevertheless , significantly increased by the intervention . Levels of SCFA were not changed significantly . Of the measured immune markers , PGE2 levels were different between treatments and IgA levels changed over time . These changes were modest which may relate to the fact that the volunteers were healthy . Spermidine levels changed over time which may suggest an improved mucosal integrity and intestinal motility . The results suggest that consumption of lactitol combined with L. acidophilus NCFM twice daily may improve some markers of the intestinal microbiota composition and mucosal functions Although non-alcoholic fatty liver disease ( NAFLD ) is the leading aetiology of liver disorders in the world , there is no proven treatment for NAFLD patients with normal or low BMI . The aim of this study was to evaluate the efficacy of synbiotics supplementation in NAFLD patients with normal or low BMI . In this r and omised , double-blind , placebo-controlled , clinical trial , fifty patients with NAFLD were assigned to take either a synbiotic supplement or a placebo capsule for 28 weeks . Both groups were advised to follow a healthy lifestyle . At the end of the study , hepatic steatosis and fibrosis reduced in both groups ; however , the mean reduction was significantly greater in the synbiotic group rather than in the placebo group ( P<0·001 ) . Furthermore , serum levels of fasting blood sugar , TAG and most of the inflammatory mediators reduced in the synbiotic group significantly compared with the placebo group ( P<0·05 ) . Our results provide evidence that synbiotic supplementation improves the main features of NAFLD in patients with normal and low BMI , at least partially through reduction in inflammatory indices . Further studies are needed to address the exact mechanism of action of these effects Background / Aims Non-alcoholic fatty liver disease ( NAFLD ) is one of the most prevalent chronic liver diseases in recent years . The aim of this study was to evaluate the effects of sitagliptin with and without a synbiotic supplement in the treatment of patients with NAFLD . Methods In total , 138 NAFLD patients aged 18 - 60 years were enrolled in the study . Patients were r and omized to one of the following treatments for 16 weeks : Group I ( n=68 ) , sitagliptin 50 mg daily plus placebo ( one capsule per day ) or group II ( n=70 ) sitagliptin 50 mg daily plus synbiotic ( one capsule per day ) . Changes in fasting blood glucose ( FBS ) , liver enzymes , lipid profile , and body mass index were compared between the groups . Results The mean change in FBS  with sitagliptin-placebo from baseline was -10.47±5.77 mg/dL , and that with sitagliptin-synbiotic was -13.52±4.16 mg/dL. There was a significant difference between the groups ( P<0.001 ) . The mean change in cholesterol ( Chol ) was -8.34±28.83 mg/dL with sitagliptin-placebo and -21.25±15.50 mg/dL with sitagliptinsynbiotic . There was a significant difference between the two groups ( P=0.029 ) . The administration of sitagliptin-placebo induced an increase of 6.13±27.04 mg/dL in low density lipoprotein ( LDL ) , whereas sitagliptin-synbiotic induced a decrease of 14.92±15.85 mg/dL in LDL . A significant difference was observed between the two groups ( P<0.001 ) . On the other h and , in the sitagliptin-synbiotic group , there was significant improvement in aspartate aminotransferase ( AST ) level  compared to the sitagliptin-placebo group ( P=0.018 ) . Conclusions Sitagliptin-synbiotic produced greater improvement in FBS , AST , Chol , and LDL compared to sitagliptin alone in patients with NAFLD Background Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in developed and developing countries . The use of synbiotics has been proposed as a probable management strategy for patients with NAFLD . Objective We investigated the effects of synbiotic yogurt on hepatic steatosis and liver enzymes as primary outcomes and on oxidative stress markers , adipokine concentration , and gut peptide concentration as secondary outcomes in patients with NAFLD . Methods In this 24-wk , open-label , r and omized controlled clinical trial , 102 patients [ 50 men and 52 women ; mean age : 40 y ; body mass index ( in kg/m2 ) ( mean ± SD ) : 31.2 ± 4.9 ] were r and omly assigned to 3 groups , including 2 intervention groups and 1 control group . The intervention groups consumed 300 g synbiotic yogurt containing 108 colony-forming units Bifidobacterium animalis/mL and 1.5 g inulin or conventional yogurt daily and were advised to follow a healthy lifestyle ( i.e. , diet and exercise ) . The control group was advised to follow a healthy lifestyle alone . We evaluated differences between groups in liver function measures by using repeated- measures ANOVA , ANCOVA , and logistic regression . Results At the end of the study , the grade s of NAFLD , as determined by ultrasonography , showed a significant decrease in the synbiotic group compared with the conventional and control groups ( P < 0.001 ) . The following significant mean ± SD decreases were seen in the synbiotic , conventional , and control groups , respectively : serum concentration of alanine aminotransferase ( -14.5 ± 15.6 compared with 4.6 ± 15.4 and 3.1 ± 14.4 IU/L ; P = 0.008 ) , aspartate aminotransferase ( -7.5 ± 6.1 compared with 3.0 ± 8.2 and 3.1 ± 5.7 IU/L ; P < 0.001 ) , alkaline phosphatase ( -26.2 ± 16.8 compared with 3.4 ± 30.1 and 1.5 ± 31.9 IU/L ; P = 0.024 ) , and γ-glutamyltransferase ( -6.0 ± 6.0 compared with 1.0 ± 6.4 and 7.6 ± 11.4 IU/L ; P < 0.001 ) . Conclusion Synbiotic yogurt consumption improved hepatic steatosis and liver enzyme concentrations in patients with NAFLD . This trial was registered at the Iranian Registry of Clinical Trials website ( www.i rct .ir ) as I RCT 2017020932417N2
target: The effects are more pronounced when synbiotics supplements are consumed for > 8 weeks .
  Synbiotic supplements may be beneficial to improve lipid profile , especially when they are consumed for > 8 weeks
background: Existing evidence on the possible effects of synbiotics on lipid profile is inconclusive .
  The aim of the present systematic review was to clarify the effects of synbiotics consumption on lipid profile .