Synbiotic Supplementation Modulates Gut Microbiota, Regulates ß-Catenin Expression and Prevents Weight Gain in ob/ob Mice: Preliminary Findings.

BACKGROUND: Obesity is one of the main health problems in the world today, and dysbiosis seems to be one of the factors involved. The aim of this study was to examine the impact of synbiotic supplementation on obesity and the microbiota in ob/ob mice. Twenty animals were divided into four groups: obese treated (OT), obese control (OC), lean treated (LT) and lean control (LC). All animals received a standard diet for 8 weeks. The treated groups received a synbiotic (Simbioflora-Invictus Farmanutrição Ltd., Sao Paulo, Brazil) in water, while the nontreated groups received only water. After 8 weeks, all animals were sacrificed, and gut tissue and stool samples were collected for mRNA isolation and microbiota analysis, respectively. ß-Catenin, occludin, cadherin and zonulin in the gut tissue were analyzed via RT-qPCR. Microbiome DNA was extracted from stool samples and sequenced using an Ion PGM Torrent platform. RESULTS: Synbiotic supplementation reduced body weight gain in the OT group compared with the OC group (p = 0.0398) and was associated with an increase in Enterobacteriaceae (p = 0.005) and a decrease in Cyanobacteria (p = 0.047), Clostridiaceae (p = 0.026), Turicibacterales (p = 0.005) and Coprococcus (p = 0.047). On the other hand, a significant reduction in Sutterella (p = 0.009) and Turicibacter (p = 0.005) bacteria was observed in the LT group compared to the LC group. Alpha and beta diversities were different among all treated groups. ß-Catenin gene expression was significantly decreased in the gut tissue of the OT group (p ≤ 0.0001) compared to the other groups. No changes were observed in occludin, cadherin or zonulin gene expression in the gut tissue. CONCLUSIONS: Synbiotic supplementation prevents excessive weight gain, modulates the gut microbiota, and reduces ß-catenin expression in ob/ob mice.

Synbiotic supplementation for glycemic status in pregnant women: a meta-analysis of randomized clinical trials.

BACKGROUND: The effect of synbiotic supplementation on glycemic status in pregnant women remained controversial and this meta-analysis aimed to explore the efficacy of synbiotic supplementation on glycemic status in pregnant women. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases and randomized controlled trials (RCTs) assessing the effect of synbiotic on glycemic status in pregnant women were included. The meta-analysis was performed using the random-effect model. RESULTS: Four RCTs were included in the meta-analysis. Overall, compared with control intervention in pregnant women, synbiotic supplementation was associated with significantly reduced serum insulin (SMD = -0.69; 95%CI = -1.06 to -0.32; p = .0002) and homoeostasis model assessment of insulin resistance (HOMA-IR, SMD = -0.53; 95%CI = -0.87 to -0.18; p = .003), but had no significant effect on fasting plasma glucose (FPG, SMD = -0.16; 95%CI = -0.43 to 0.11; p = .24), quantitative insulin sensitivity check index (QUICKI, SMD = 0.54; 95%CI = -0.10 to 1.18; p = .10) or CRP (SMD = -0.29; 95%CI = -1.23 to 0.64; p = .54). CONCLUSIONS: Synbiotic supplementation was beneficial to glycemic control in pregnant women.

Dietary administration of ß-1,3/1,6-glucan and Lactobacillus plantarum improves innate immune response and increases the number of intestine immune cells in roach (Rutilus rutilus).

BACKGROUND: The aim of the study has been to compare the effect of dietary supplementation of ß-1,3/1,6-glucan, Lactobacillus plantarum bacteria or their mixture on the growth performance, selected parameters of the immune system as well as the liver and intestinal histology of roach. Fish were fed for 14 days with four different diets, each treatment being carried out in triplicate. In control group, fish were fed dry commercial starter feed Aller Performa 2 (Aller Aqua, Denmark). The other experimental fish groups received the same commercial starter feed supplemented with: 1% ß-1,3/1,6-glucan (Leiber® Beta-S) in group G; 108 cfu L. plantarum g- 1 in group L; 1% ß-1,3/1,6-glucan + 108 cfu L. plantarum g- 1 in group G + L. The stimulating effect of the tested preparations was evaluated once the feeding with commercial feed exclusively was resumed and 2 weeks afterwards. RESULTS: No effect on the survivability and growth performance of the fish was observed in any of the groups. Supplementation of feed with ß-1,3/1,6-glucan improved (P < 0.05) selected parameters of innate humoral immunity and the pinocytotic activity of phagocytes. Increased respiratory burst activity of head kidney phagocytes (RBA) was observed in groups L and G + L (P < 0.05), and the effect persisted for 2 weeks after the commercial feed regime was resumed. An analogous tendency was determined for the killing activity of phagocytes (PKA) of the head kidney with respect to Aeromonas hydrophila, although this effect appeared only during the feed supplementation period. Supplying roach with ß-1,3/1,6-glucan, singly or with L. plantarum, had no effect (P > 0.05) on the proliferation of mitogen-activated lymphocytes. However, an increase in the number of CD3-positive cells and goblet cells was noticed in the digestive system of the L group fish (P < 0.05). CONCLUSIONS: The results show that feeding fish with added L. plantarum and ß-1,3/1,6-glucan stimulates the non-specific resistance mechanisms and raises the counts of intestinal immune cells. Synbiotic may help to control serious bacterial diseases and offer an alternative to antibiotics commonly used in fish farming, and its prolonged immunostimulatory effect could increase fish surviving after release to the natural environment.

The Effect of Synbiotic Supplementation on Growth Parameters in Mild to Moderate FTT Children Aged 2-5 Years.

Synbiotic (probiotic bacteria and prebiotic) has beneficial effects on the gastrointestinal tract. This study was designed to investigate the effect of synbiotic supplementation on the growth of mild to moderate failure to thrive (FTT) children. A randomized, triple-blind, placebo-controlled trial was conducted involving 80 children aged 2-5 years with mild to moderate FTT, who were assigned at random to receive synbiotic supplementation (109 colony-forming units) or placebo for 30 days. The weights, height, and BMI were recorded in a structured diary, and the questionnaires were completed to monitor the numbers of infection episodes, gastrointestinal problems, admission to hospital, and appetite improvement during the study. Sixty-nine children completed the study. There were no differences in the demographic characteristic between the two groups. The mean weight was similar at baseline. After 30 days of intervention, the mean weight of the participants in the synbiotic group increased significantly than those in the placebo group (600 ± 37 vs. 74 ± 32 g/month P 0.000). BMI changes in synbiotic and placebo group were 0.44 and 0.07 kg/m2, and that the differences among the two groups were significant.(P 0.045) Furthermore, the height increment in synbiotic and placebo group was 0.41 and 0.37 cm respectively with no significant difference (P 0.761). Administration of 30-day synbiotic supplementation may significantly improve weight and BMI in Iranian children with mild to moderate FTT, but there is no effect on the height in this study. Further studies should be designed to found out the effect of synbiotic on growth parameters in undernourished and well-nourished children.

Effect of Synbiotic Supplementation in a Very-Low-Calorie Ketogenic Diet on Weight Loss Achievement and Gut Microbiota: A Randomized Controlled Pilot Study.

SCOPE: Little is known about the changes that a very-low-calorie ketogenic diet (VLCKD) produces in gut microbiota or the effect of synbiotics during the diet. The aim of this study is to evaluate changes in gut microbiota produced by a VLCKD and synbiotic supplementation. METHODS AND RESULTS: A randomized, single-blind, parallel-design trial is conducted in 33 obese patients who follow a weight-loss program (PnK-Method) that include a VLCKD followed by a low-calorie diet (LCD). Subjects are randomly allocated to three groups: one supplemented with synbiotics, a second group supplemented with a placebo during the VLCKD and synbiotics during the LCD phase, and a control group given a placebo. Although symbiotic administration do not produce an effect on microbial diversity, an increase in short-chain fatty aciding producing bacteria and anti-inflammatory mediator signals such as Odoribacter and Lachnospira is shown. The administration of Bifidobacterium animalis subsp. lactis and prebiotics fiber during the LCD is significantly associated with the percentage of weight loss and change in glucose, C-reactive protein and lipopolysaccharide-binding protein. CONCLUSIONS: VLCKD produces important changes in gut microbiota. The administration of synbiotics during VLCKD can improve weight loss through the amelioration of inflammation, which may be mediated by the gut microbiota.

Synbiotic supplementation is not effective on breast milk selenium concentrations and growth of exclusively breast fed infants: a pilot study.

In this randomized, double-blind, placebo-controlled trial, 57 lactating mothers were randomly allocated into two groups to receive a daily supplement of synbiotic (n = 30) which contained different probiotic strains (2.0 × 108 CFU) and fructooligosaccharide (394 mg) or a placebo (n = 27) for 30 days. Dietary intake was collected from lactating women by 24-hour recall method. Breast milk selenium contents were determined by atomic absorption spectrometry with graphite furnace. Weight for age Z-score (WAZ) and Height for age Z-score (HAZ) were evaluated for infants. Data analyses were assessed using nutritionist IV, Epi Info and SPSS software and presented as mean ± sd or SEM. The total mean breast milk selenium levels were 50.1 ± 16.1 mcg L-1. At the baseline, the mean breast milk selenium concentrations in the synbiotic and placebo groups were 51.7 ± 20.2 and 48.5 ± 12.1 mcg L-1. The mean breast milk selenium levels increased and decreased in the symbiotic and placebo groups respectively, which were not significant (p > 0.05). Also, comparison of the changes in breast milk selenium concentration showed no significant difference between the two study groups after the intervention. At the baseline, the mean WAZ and HAZ of infants whose mothers' milk selenium was more than 60 mcg/l was significantly (P < 0.05) higher than for others. In this pilot study, no significant effect was observed by synbiotic supplementation, however, for concise conclusion, more human studies with higher doses of supplements and longer duration of supplementation are needed to determine the effects of synbiotic supplementation on breast milk selenium contents and infants' growth.

The Effects of Synbiotic Supplementation on Carotid Intima-Media Thickness, Biomarkers of Inflammation, and Oxidative Stress in People with Overweight, Diabetes, and Coronary Heart Disease: a Randomized, Double-Blind, Placebo-Controlled Trial.

Synbiotics are known to exert multiple beneficial effects, including anti-inflammatory and antioxidant actions. The aim of this study was to evaluate the effects of synbiotic supplementation on carotid intima-media thickness (CIMT), biomarkers of inflammation, and oxidative stress in people with overweight, diabetes, and coronary heart disease (CHD). This randomized, double-blind, placebo-controlled trial was conducted and involved 60 people with overweight, diabetes, and CHD, aged 50-85 years old. Participants were randomly allocated into two groups to take either synbiotic supplements containing three probiotic bacteria spices Lactobacillus acidophilus strain T16 (IBRC-M10785), Lactobacillus casei strain T2 (IBRC-M10783), and Bifidobacterium bifidum strain T1 (IBRC-M10771) (2 × 109 CFU/g each) plus 800 mg inulin or placebo (n = 30 each group) for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention period to determine metabolic variables. After the 12-week intervention, compared with the placebo, synbiotic supplementation significantly reduced serum high-sensitivity C-reactive protein (hs-CRP) (- 3101.7 ± 5109.1 vs. - 6.2 ± 3163.6 ng/mL, P = 0.02), plasma malondialdehyde (MDA) (- 0.6 ± 1.0 vs. - 0.1 ± 0.3 µmol/L, P = 0.01), and significantly increased nitric oxide (NO) levels (+ 7.8 ± 10.3 vs. - 3.6 ± 6.9 µmol/L, P < 0.001). We did not observe any significant changes of synbiotic supplementation on other biomarkers of oxidative stress and CIMT levels. Overall, synbiotic supplementation for 12 weeks among people with overweight, diabetes, and CHD had beneficial effects on serum hs-CRP, plasma NO, and MDA levels; however, it did not have any effect on other biomarkers of oxidative stress and CIMT levels.

The Effects of Synbiotic Supplementation on Metabolic Status in Women With Polycystic Ovary Syndrome: a Randomized Double-Blind Clinical Trial.

Data on the effects of synbiotic supplementation on glycemic control, lipid profiles, and atherogenic index of plasma (AIP) of women with polycystic ovary syndrome (PCOS) are limited. The purpose of this study was to assess the effects of synbiotic supplementation on glycemic control and lipid profiles in women with PCOS. A prospective, randomized, double-blind, placebo-controlled trial was done at the Naghavi Hospital affiliated to Kashan University of Medical Sciences, Kashan, Iran, between April 2017 and June 2017. Sixty women with PCOS were randomized to intake synbiotic capsule containing Lactobacillus acidophilus strain T16 (IBRC-M10785), Lactobacillus casei strain T2 (IBRC-M10783), and Bifidobacterium bifidum strain T1 (IBRC-M10771) (2 × 109 CFU/g each) plus 800 mg inulin (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention to determine related variables. Compared with the placebo, synbiotic supplementation resulted in a significant reduction in serum insulin concentrations (- 2.8 ± 4.1 vs. + 1.8 ± 6.4 µIU/mL, P = 0.002) and homeostasis model of assessment-insulin resistance (- 0.7 ± 1.0 vs. + 0.4 ± 1.5, P = 0.002), and a significant elevation in the quantitative insulin sensitivity check index (+ 0.01 ± 0.01 vs. - 0.01 ± 0.03, P < 0.001). In addition, significant decreases in serum triglycerides (- 16.2 ± 31.4 vs. + 5.8 ± 23.1 mg/dL, P = 0.003), VLDL-cholesterol concentrations (- 3.3 ± 6.3 vs. + 1.1 ± 4.6 mg/dL, P = 0.003), and AIP (- 0.05 ± 0.08 vs. - 0.003 ± 0.10 mg/dL, P = 0.03) were seen following the supplementation of synbiotic compared with the placebo. Overall, we found that synbiotic supplementation to women with PCOS for 12 weeks had beneficial effects on markers of insulin resistance, triglycerides, VLDL-cholesterol concentrations, and AIP, but did not influence other lipid profiles. Trial registration: www.irct.ir: IRCT201604015623N71.

The Effects of Synbiotic Supplementation on Metabolic Status in Diabetic Patients Undergoing Hemodialysis: a Randomized, Double-Blinded, Placebo-Controlled Trial.

This study was conducted to evaluate the effects of synbiotic supplementation on metabolic profiles in diabetic patients undergoing hemodialysis (HD). This randomized, double-blinded, placebo-controlled clinical trial was performed in 60 diabetic HD patients. Participants were randomly assigned into two groups to receive either synbiotic capsule, containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum (2 × 109 CFU/g each), plus 0.8 g/day of inulin (n = 30) or placebo (n = 30) for 12 weeks. Synbiotic supplementation significantly decreased fasting plasma glucose (ß - 13.56 mg/dL; 95% CI, - 23.82, - 3.30; P = 0.01), insulin levels (ß - 5.49 µIU/mL; 95% CI, - 6.92, - 4.05; P < 0.001), and insulin resistance (ß - 2.25; 95% CI, - 3.02, - 1.48; P < 0.001), while increased the quantitative insulin sensitivity check index (ß 0.02; 95% CI, 0.01, 0.02; P < 0.001) compared with the placebo. Additionally, synbiotic intake resulted in a significant reduction in high-sensitivity C-reactive protein (ß - 2930.48 ng/mL; 95% CI, - 3741.15, - 2119.80; P < 0.001) and malondialdehyde levels (ß - 0.60 µmol/L; 95% CI, - 0.99, - 0.20; P = 0.003). Moreover, we found a significant increase in total antioxidant capacity (ß 142.99 mmol/L; 95% CI, 61.72, 224.25; P = 0.001) and total glutathione levels (ß 131.11 µmol/L; 95% CI, 89.35, 172.87; P < 0.001) in the synbiotic group compared with the placebo group. Overall, synbiotic supplementation for 12 weeks had beneficial effects on glycemic control, biomarkers of inflammation, and oxidative stress in diabetic patients under HD. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT2017090133941N17). http://www.irct.ir: IRCT2017090133941N17.

The Effects of Synbiotic Supplementation on Pregnancy Outcomes in Gestational Diabetes.

Synbiotics are known to exert multiple beneficial effects, including anti-inflammatory and antioxidative actions. This study was designed to evaluate the effects of synbiotic administration on biomarkers of inflammation, oxidative stress, and pregnancy outcomes among gestational diabetic (GDM) women. This randomized, double-blind, placebo-controlled clinical trial was carried out among 60 subjects with GDM who were not on oral hypoglycemic agents. Patients were randomly assigned to consume either one synbiotic capsule containing Lactobacillus acidophilus strain T16 (IBRC-M10785), L. casei strain T2 (IBRC-M10783), and Bifidobacterium bifidum strain T1 (IBRC-M10771) (2 × 109 CFU/g each) plus 800 mg inulin (HPX) (n = 30) or placebo (n = 30) for 6 weeks. Compared with the placebo, synbiotic supplementation significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (- 1.9 ± 4.2 vs. +1.1 ± 3.5 mg/L, P = 0.004), plasma malondialdehyde (MDA) (- 0.1 ± 0.6 vs. + 0.3 ± 0.7 µmol/L, P = 0.02), and significantly increased total antioxidant capacity (TAC) (+ 70.1 ± 130.9 vs. - 19.7 ± 124.6 mmol/L, P = 0.009) and total glutathione (GSH) levels (+ 28.7 ± 61.5 vs. - 14.9 ± 85.3 µmol/L, P = 0.02). Supplementation with synbiotic had a significant decrease in cesarean section rate (16.7 vs. 40.0%, P = 0.04), lower incidence of hyperbilirubinemic newborns (3.3 vs. 30.0%, P = 0.006), and newborns' hospitalization (3.3 vs. 30.0%, P = 0.006) compared with the placebo. Synbiotic supplementation did not affect plasma nitric oxide (NO) levels and other pregnancy outcomes. Overall, synbiotic supplementation among GDM women for 6 weeks had beneficial effects on serum hs-CRP, plasma TAC, GSH, and MDA; cesarean section; incidence of newborn's hyperbilirubinemia; and newborns' hospitalization but did not affect plasma NO levels and other pregnancy outcomes. http://www.irct.ir : www.irct.ir : IRCT201704205623N108.

The effects of synbiotic supplementation on markers of insulin metabolism and lipid profiles in gestational diabetes: a randomised, double-blind, placebo-controlled trial.

To the best of our knowledge, data on the effects of synbiotic supplementation on markers of insulin metabolism and lipid concentrations in patients with gestational diabetes mellitus (GDM) are scarce. The aim of the current study was to determine the effects of synbiotic supplementation on markers of insulin metabolism and lipid profiles in GDM patients. In total, seventy patients with GDM aged 18-40 years were assigned to two groups - the synbiotic group (n 35) and the placebo group (n 35) - in this randomised, double-blind, placebo-controlled trial. Patients in the synbiotic group received a daily capsule that contained three viable and freeze-dried strains: Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum (2×109 colony-forming units/g each) plus 800 mg inulin for 6 weeks. Fasting blood samples were collected at the beginning and week 6 to quantify related markers. After 6 weeks of intervention, compared with the placebo, synbiotic supplementation led to a significant decrease in serum insulin levels (-1·5 (sd 5·9) v. +4·8 (sd 11·5) µIU/ml, P=0·005), homoeostatic model assessment for insulin resistance (-0·4 (sd 1·3) v. +1·1 (sd 2·7), P=0·003) and homoeostatic model assessment for ß cell function (-5·1 (sd 24·2) v. +18·9 (sd 45·6), P=0·008) and a significant increase in quantitative insulin sensitivity check index (+0·01 (sd 0·01) v. -0·007 (sd 0·02), P=0·02). In addition, synbiotic intake significantly decreased serum TAG (-14·8 (sd 56·5) v. +30·4 (sd 37·8) mg/dl, P<0·001) and VLDL-cholesterol concentrations (-3·0 (sd 11·3) v. +6·1 (sd 7·6) mg/dl, P<0·001) compared with the placebo. Overall, the results of this study demonstrate that taking synbiotic supplements for 6 weeks among patients with GDM had beneficial effects on markers of insulin metabolism, TAG and VLDL-cholesterol concentrations.