Synbiotics Easing Renal Failure by Improving Gut Microbiology II (SYNERGY II): A Feasibility Randomized Controlled Trial

Synbiotics have emerged as a therapeutic strategy for modulating the gut microbiome and targeting novel cardiovascular risk factors, including uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS). This study aims to evaluate the feasibility of a trial of long-term synbiotic supplementation in adults with stage 3–4 chronic kidney disease (CKD). Adult participants with CKD and estimated glomerular filtration rate (eGFR) of 15–60 mL/min/1.73 m2) were recruited between April 2017 and August 2018 to a feasibility, double-blind, placebo-controlled, randomized trial of synbiotic therapy or matched identical placebo for 12 months. The primary outcomes were recruitment and retention rates as well as acceptability of the intervention. Secondary outcomes were treatment adherence and dietary intake. Exploratory outcomes were evaluation of the cardiovascular structure and function, serum IS and PCS, stool microbiota profile, kidney function, blood pressure, and lipid profile. Of 166 potentially eligible patients, 68 (41%) were recruited into the trial (synbiotic n = 35, placebo n = 33). Synbiotic and placebo groups had acceptable and comparable 12-month retention rates (80% versus 85%, respectively, p = 0.60). Synbiotic supplementation altered the stool microbiome with an enrichment of Bifidobacterium and Blautia spp., resulting in a 3.14 mL/min/1.73 m2 (95% confidence interval (CI), −6.23 to −0.06 mL/min/1.73 m2, p < 0.01) reduction in eGFR and a 20.8 µmol/L (95% CI, 2.97 to 38.5 µmol/L, p < 0.01) increase in serum creatinine concentration. No between-group differences were observed in any of the other secondary or exploratory outcomes. Long-term synbiotic supplementation was feasible and acceptable to patients with CKD, and it modified the gastrointestinal microbiome. However, the reduction in kidney function with synbiotics warrants further investigation.

Potential improvements of the cognition of piglets through a synbiotic supplementation from 1 to 28 days via the gut microbiota

The influence of feed supplements on behavior and memory has been recently studied in livestock. The objectives of the study were to evaluate the effects of a synbiotic on: an episodic-like (SOR: Spontaneous Object Recognition), a working (BARR: Fence barrier task), a long-term (TMAZE: Spatial T-maze task) memory test and on gut microbiota composition. Eighteen female piglets were supplemented from 1 to 28 days of age with a synbiotic (SYN), while 17 served as control (CTL). Feces were collected on days 16, 33 and 41 for 16S rRNA gene composition analyses. In the SOR, SYN piglets interacted more quickly with the novel object than CTL piglets. In the BARR, SYN piglets had shorter distances to finish the test in trial 3. In the TMAZE, SYN piglets were quicker to succeed on specific days and tended to try the new rewarded arm earlier during the reversal stage. Difference of microbiota composition between treatments was nonexistent on D16, a tendency on D33 and significant on D41. The synbiotic supplement may confer memory advantages in different cognitive tasks, regardless of the nature of the reward and the memory request. Difference in memory abilities can potentially be explained by differences in microbiota composition.

Synbiotic Supplementation Modulates Gut Microbiota, Regulates Beta-Catenin Expression And Prevents Weight Gain in ob/ob Mice

Background: The aim of this study was to examine the impact of synbiotic supplementation in obesity and microbiota in ob/ob mice. 20 animals were divided into four groups: Obese Treated (OT), Control (OC), Lean Treated (LT) and Control (LC). All animals received standard diet for 8 weeks. Treated groups received a synbiotic in water while nontreated groups received water. After 8 weeks, all animals were sacrificed and gut tissue mRNA isolation and stool samples by microbiota analysis were collected. Beta-catenin, occludin, cadherin and zonulin were analyzed in gut tissue by RT-qPCR. Results: The synbiotic supplementation reduced body weight gain in OT comparing with OC (p=0.0398), increase of Enterobacteriaceae (p=0.005) and decrease of Cyanobacteria (p=0.047), Clostridiaceae (p=0.026), Turicibacterales (p=0.005) and Coprococcus (p=0.047). A significant reduction of Sutterella bacteria (p=0.009) and Turicibacter (p=0.005) was observed in LT compared to LC. Alpha and beta diversities were differ between all treated groups. Beta-catenin gene expression was significantly decreased in the gut tissue of OT (p≤0.0001) when compared to other groups. No changes were observed in occludin, cadherin and zonulin gene expression in the gut tissue. Conclusion: The synbiotics supplementation prevents excessive weight gain, modulates the gut microbiota, and reduces beta-catenin expression in ob/ob mice.

Effect of synbiotic supplementation on asprosin level in high fat diet-induced metabolic disorder in pregnant rats

Synbiotic supplementation can improve metabolic disorders. The aim of this study was to assess the impact of synbiotic supplementation on the levels of asprosin, lipid profile, glucose, and insulin resistance in pregnant rats fed a high-fat diet (HFD). Rats were divided into three groups: control group (fed base chow), HFD group, and HFD + synbiotic group. Levels of blood glucose, total cholesterol, triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, and asprosin levels were measured. Birth weight of offspring in the HFD + synbiotic group was significantly lower than in the HFD group. Similarly, serum asprosin, insulin, insulin resistance, TG and total cholesterol levels in the HFD + symbiotic group were significantly lower than in the HFD group. Asprosin levels had a significant and positive correlation between food intake in the first ten days of the experiment and gestation period, fasting blood sugar (FBS), TG, and homeostatic model assessment (HOMA) index. Moreover, asprosin levels had a significant and negative correlation with HDL and insulin levels. Results showed, synbiotic supplementation has beneficial effects on obese animals and improves weight gain during pregnancy, pup birth weight, FBS, insulin resistance and lipid profile. These advantages of synbiotic supplementation could be mediated by reducing serum asprosin levels.

Synbiotic supplementation attenuates the promoting effect of indole-3-carbinol on colon tumorigenesis

Indole-3 carbinol (I3C) has shown dual effects on the promotion and progression stages of colon carcinogenesis while synbiotics (Syn) have exerted anti-carcinogenic activities in most rodent studies. This study aimed to investigate the effects of I3C given alone or together with a Syn intervention on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. All animals were given four subcutaneous DMH injections (4×40 mg/kg bodyweight, twice a week for two weeks) and then received either basal diet (G1), basal diet containing I3C (1g/kg chow) (G2) or basal diet containing I3C+Syn (I3C + inulin 50g/kg chow + Bifidobacterium lactis BB-12®), 2.5×1010 cfu/g of basal diet), (G3) for 21 weeks. Dietary I3C (G2) significantly increased tumour volume and cell proliferation when compared to the DMH control group (G1). Syn intervention (G3) significantly reduced tumour volume and cell proliferation when compared to I3C (G2). The colon tumours found were classified into well-differentiated tubular adenomas or adenocarcinomas. Dietary I3C or I3C+Syn did not significantly affect the incidence and the multiplicity of tumours in comparison with the DMH control group. Furthermore, Syn intervention (G3) increased Gstm1 and reduced Mapk9 gene expression in colonic tumours. The findings of the present study show that the dietary I3C shows a weak promoting activity, while the combination with Syn ameliorates I3C effects.

The Effect of Probiotics or Synbiotics on the Hypertensive Disorders of Pregnant Women with Gestational Diabetes: A Systematic Review and Meta-analysis

Introduction:Antioxidants and anti-inflammatory drugs have been suggested to treat preeclampsia. This systematic review and meta-analysis was conducted to investigate the efficacy of probiotic or synbiotic supplementation on hypertensive disorders in women with gestational diabetes mellitus (GDM).Methods:The databases including Cochrane, Embase, Ovid, ProQuest, Scopus, Web of Science, and PubMed were systematically searched for collecting the randomized controlled trials (RCTs) investigating the efficacy of probiotic or synbiotic supplementation versus placebo on hypertensive disorders and pregnancy outcomes in GDM until July 2020.Results:Five RCTs with a total sample size of 402 women were included in the meta-analysis. There was no significant decline in systolic blood pressure (standardized mean difference [SMD] = -3.41, 95% confidence interval [CI] = -8.32 to 1.50, P = 0.17), diastolic blood pressure (SMD = -5.11, 95% CI = -14.20 to -3.98, P = 0.27), preeclampsia (odds ratio [OR] = 1.56, 95% CI = 0.61 to 3.98, P = 0.35), cesarean section (OR = 0.52, 95% CI = 0.18 to 1.50, P = 0.23), and macrosomia (OR = 0.81, 95% CI = 0.41 to 1.57, P = 0.53). No significant increase was observed in terms of 5-minute Apgar (SMD = 0.16, 95% CI = -0.06 to 0.39, P = 0.15, I2= 0%), birth weight (SMD = -0.18, 95% CI = -0.43 to 0.06, P = 0.13, I2= 0%), and gestational age (SMD = 0.13, 95% CI = -0.11 to 0.37, P = 0.28, I2= 0%).Conclusion:Probiotic or synbiotic supplements are not associated with significant effects on pregnancy outcomes in GDM. However, due to the limited number of studies in this regard and heterogeneity between studies, future high-quality RCTs are recommended.