Are probiotics effective in reducing the metabolic side effects of psychiatric medication? A scoping review of evidence from clinical studies.

The psychopharmacological treatment of patients with schizophrenia or depression is often accompanied by serious side effects. In particular, the clinical findings of weight gain are worrying, as this side effect can lead to various medical sequelae in the future. However, the treatment of metabolic changes in psychiatric patients is often neglected or unsuccessful. An improved knowledge of possible therapeutic approaches is needed. The aim of this study was to provide an overview of the utilisation and effectiveness of probiotics in reducing weight gain in patients with severe mental illness. A scoping review of studies published until 15 June 2022 was conducted to identify studies using probiotics in people with schizophrenia or depression. We systematically searched the databases EMBASE, PubMed (MEDLINE), Web of Science and SCOPUS with a predefined search string. In addition, reference lists of relevant publications were examined for additional studies. The studies were assessed by two reviewers. The primary outcomes were weight-related measurements. The secondary outcomes were metabolic blood parameters and gut microbiota. Four studies ultimately met the inclusion criteria. Two studies in which probiotics were administered did not find significant effects on pharmacologically induced weight gain. The other two studies examined the effects of synbiotics (a combination of probiotics and prebiotics). Interestingly, less weight gain was observed in individuals with this combined intervention. Adjustments in diet can be helpful and are generally well-accepted interventions in the fight against pharmacologically induced weight gain. The clinical use of probiotics and prebiotics (or synbiotics) as dietary interventions may represent a promising additional strategy in this regard. However, the few studies available showed no clear conclusions.

Efficacy and safety of probiotics, prebiotics, and synbiotics for the prevention of colorectal cancer and precancerous lesion in high-risk populations: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Colorectal cancer (CRC) is highly prevalent worldwide and is a leading cause of cancer-related death. Probiotics, prebiotics, and synbiotics have recently attracted attention as preventive measures against colorectal neoplasms. We aimed to analyze the findings of randomized controlled trials (RCTs) on the effects of probiotics, prebiotics, and synbiotics in patients at a high risk of CRC, outlining the challenges and future prospects of using probiotics to prevent colorectal tumors and providing evidence for clinical physicians in particular. METHODS: PubMed, EMBASE, and the Cochrane Library databases were searched for relevant studies published up to January 7, 2022. RCTs conducted on populations with a high risk of CRC who received probiotics, prebiotics or synbiotics in comparison with placebo, candidate agent or no treatment were included. The primary outcome was the incidence or recurrence of any colorectal neoplasms. Additional outcomes included their effects on the diversity of gut microbiota and relevant inflammatory biomarkers. Safety outcomes were also analyzed. Two authors independently screened and selected studies based on pre-specified eligible criteria, performed data extraction and risk-of-bias assessment independently. RESULTS: Nine RCTs were included in the systematic review and meta-analysis. Probiotic supplementation significantly reduced adenoma incidence, but no significant benefit was observed in CRC incidence. Additionally, probiotics modulated gut microbiota and inflammatory biomarkers. CONCLUSION: Probiotics may have beneficial effects in the prevention of CRC. More RCTs with larger sample sizes are warranted to further confirm these findings.

The effect of probiotic and synbiotic supplementation on lipid parameters among patients with cardiometabolic risk factors: a systematic review and meta-analysis of clinical trials.

Although the available evidence emphasizes the beneficial effects of probiotics in normalizing various cardiometabolic markers, there is still substantial uncertainty in this regard. Thus, we set out to determine the effect sizes of probiotics on blood lipid parameters more coherently. A systematic literature search of the Medline (PubMed) and Scopus databases was conducted from inception to 12 February 2021, applying both MeSH terms and free text terms to find the relevant randomized controlled trials (RCTs). The meta-analysis was conducted based on a random-effect model to calculate the mean effect sizes demonstrated as weighted mean differences (WMDs) and the 95% confidence intervals (95% CIs). To explore the heterogeneity, the Cochrane χ2 test, and analysis of Galbraith plots were performed. Meta-analysis of data from 40 RCTs (n = 2795) indicated a significant decrease in serum/plasma triglyceride [WMD (95% CI) = -12.26 (-17.11 to -7.41) mg/dL; P-value <0.001; I2 (%) = 29.9; P heterogeneity = 0.034], total cholesterol (with high heterogeneity) (WMD (95% CI) = -8.43 (-11.90 to -4.95) mg/dL; P-value <0.001; I2 (%) = 56.8; P heterogeneity < 0.001), LDL-C [WMD (95% CI) = -5.08 (-7.61, -2.56) mg/dL; P-value <0.001; I2 (%) = 42.7; P heterogeneity = 0.002], and HDL-C (with high heterogeneity) (WMD (95% CI) = 1.14 (0.23, 2.05) mg/dL; P-value = 0.014; I2 (%) = 59.8; P heterogeneity < 0.001) following receiving probiotic/synbiotic supplements. Collectively, the current preliminary evidence supports the effectiveness of probiotics/synbiotics in improving dyslipidaemia and various lipid parameters more prominently among subjects with hyperlipidaemia, diabetes, and metabolic syndrome. However, large and well conducted RCTs are required to provide further convincing support for these results.

Are Probiotics and Prebiotics Safe for Use during Pregnancy and Lactation? A Systematic Review and Meta-Analysis.

Probiotic and prebiotic products have shown potential health benefits, including for the prevention of adverse pregnancy outcomes. The incidence of adverse effects in pregnant people and their infants associated with probiotic/prebiotic/synbiotic intake, however, remains unclear. The objectives of this study were to evaluate the evidence on adverse effects of maternal probiotic, prebiotic, and/or synbiotic supplementation during pregnancy and lactation and interpret the findings to help inform clinical decision-making and care of this population. A systematic review was conducted following PRISMA guidelines. Scientific databases were searched using pre-determined terms, and risk of bias assessments were conducted to determine study quality. Inclusion criteria were English language studies, human studies, access to full-text, and probiotic/prebiotic/synbiotic supplementation to the mother and not the infant. In total, 11/100 eligible studies reported adverse effects and were eligible for inclusion in quantitative analysis, and data were visualised in a GOfER diagram. Probiotic and prebiotic products are safe for use during pregnancy and lactation. One study reported increased risk of vaginal discharge and changes in stool consistency (relative risk [95% CI]: 3.67 [1.04, 13.0]) when administering Lactobacillus rhamnosus and L. reuteri. Adverse effects associated with probiotic and prebiotic use do not pose any serious health concerns to mother or infant. Our findings and knowledge translation visualisations provide healthcare professionals and consumers with information to make evidence-informed decisions about the use of pre- and probiotics.

An Updated Systematic Review With Meta-analysis: Efficacy of Prebiotic, Probiotic, and Synbiotic Treatment of Patients With Severe Acute Pancreatitis.

OBJECTIVES: The aim of this study was to systematically review the clinical outcomes of all randomized controlled trials of patients with severe acute pancreatitis (SAP) and treated with pre/pro/synbiotics. METHODS: A systematic literature search of the MEDLINE, Embase, clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials was conducted. Eligible studies were randomized controlled trials that evaluated the clinical outcomes of patients with SAP treated with pre/pro/synbiotics. RESULTS: Eleven trials comprising 930 patients were included. Patients treated with pre/pro/synbiotics had a significantly shorter hospital stay [weighted mean difference, -4.33 days; 95% confidence interval (CI), -7.71 to -0.95; P = 0.010; I2 = 66.9%] compared with control. In a subgroup analysis where only patients classified as SAP were included, those treated with pre/pro/synbiotics had lower risk of single- or multiple-organ failure (relative risk, 0.62; 95% CI, 0.44-0.88; P = 0.995; I2 = 0.0%) and decreased hospital stay (weighted mean difference, -0.65 days; 95% CI, -0.90 to -0.41; P = 0.121; I2 = 45.3%) compared with control. CONCLUSIONS: Patients with SAP treated with pre/pro/synbiotics did not have a worse clinical outcome and had lower risk of organ failure and duration of hospital stay. Further studies should examine the optimal timing, type, and dosages of these promising treatments.

Effect of probiotics, prebiotics and synbiotics for chronic bronchitis or chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Probiotics, prebiotics and synbiotics have been widely used in the treatment of respiratory diseases, but their clinical efficacy for treating chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) has not been well studied. METHODS: The following electronic databases will be searched for eligible randomized controlled trials: the Cochrane Library, EMBASE, MEDLINE, PubMed, Scopus, the Web of Science, the China National Knowledge Infrastructure, the Wanfang database, and the China Science and Technology Journal database (VIP Information Network). We will search these electronic databases weekly and extract relevant data from their inception dates until September 30, 2020. Risk of publication bias will be evaluated by the Cochrane Handbook for Systematic Reviews of Interventions. Data synthesis will be conducted using Review Manager (RevMan) version 5.3 software. Sensitivity and quality of evidence analyses will be conducted. RESULTS: This systematic review and meta-analysis will provide a high-quality synthesis from existing evidence for estimating the efficacy and safety of probiotics, prebiotics and synbiotics in the treatment of CB or COPD. CONCLUSION: This systematic review and meta-analysis will provide reliable and accurate evidence to guide the use of probiotics, prebiotics and synbiotics in the treatment of CB or COPD. REGISTRATION OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/SP35M.

Clinical evaluation of the synbiotic Prodefen Plus® in the prevention of the antibiotic-associated diarrhoea in subjects requiring antibiotic treatment.

Prodefen® is a dietary food supplement formulated as a synbiotic that has shown additional benefit to the standard supportive therapy in the management of acute viral diarrhoea in children. There is scarce evidence of this synbiotic in adults. The objective of this randomised double blind placebo-controlled clinical trial was to evaluate the efficacy and safety of Prodefen Plus® in the prevention of antibiotic-associated diarrhoea (AAD) in an adult population requiring either antibiotic treatment for an oral infection or antibiotic prophylaxis for a dental surgical procedure in a dental consultation. 151 subjects were randomised to the active (synbiotic) or control arm (placebo) for 14 days. There was a significantly higher reduction in the AAD incidence, and an improvement in the stool consistency in the active group. A higher reduction in both the frequency and duration of the diarrhoea episodes in the active group was also observed, as it was an improved perception of the diarrhoea severity. Overall, the study medication was well tolerated. In conclusion, results from this study confirm the beneficial effect of the synbiotic administered as adjuvant therapy in preventing the antibiotic-associated diarrhoea.

Probiotics, prebiotics, and synbiotics supplementation in prediabetes: protocol for a systematic review and meta-analysis.

BACKGROUND: The prevalence of prediabetes and diabetes is increasing rapidly, and 5% to 10% of prediabetic patients will develop diabetes every year. Diabetes causes major health problems as well as a large economic burden. Human studies have demonstrated the beneficial effects of probiotics, prebiotics, and synbiotics supplementation in prediabetes. However, there are no systematic reviews that explore the therapeutic efficacy of probiotics, prebiotics, and synbiotics supplementation in patients with prediabetes. Therefore, we aim to synthesize the existing evidence evaluating the effectiveness and safety of probiotics, prebiotics, and synbiotics supplementation in prediabetic patients. METHODS: We will search PubMed, EMBASE, Cochrane Library, Web of Science, the Clinical Trials.gov website, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data Knowledge Service Platform from inception to August 2020. Additionally, the search will be conducted in multiple languages. Search terms are keywords and medical subject headings related to prediabetes, probiotics, prebiotics, and synbiotics. The primary outcomes are differences in glycated hemoglobin and fasting blood glucose. The secondary outcomes are differences in fasting insulin, homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index, and adverse events. The meta-analysis will be performed using the Revman5.3.0 software provided by the Cochrane Collaboration. RESULTS: Our study will systematically evaluate the effectiveness and safety of probiotics, prebiotics, and synbiotics supplementation in prediabetes. CONCLUSION: The findings of this study will provide the best available evidence for probiotics, prebiotics, and synbiotics in the treatment of prediabetes, and provide a strong basis for clinical treatment.

Side Effects Associated with Probiotic Use in Adult Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Probiotics demonstrated to be effective in the treatment of inflammatory bowel disease (IBD). However, the safety profile of probiotics is insufficiently explored. In the present systematic review and meta-analysis, we examined the occurrence of side effects related to probiotic/synbiotic use in randomized controlled trials (RCTs) of IBD patients as compared with placebo. Eligible RCTs in adult patients with IBD were identified by accessing the Medline database via PubMed, EMBASE, CENTRAL and the Cochrane central register of controlled trials up to December 2018. Occurrence of side effects was retrieved and recorded. Data were pooled and the relative risks (RRs) with their 95% confidence intervals (CIs) were calculated. The low-moderate study heterogeneity, assessed by the I2 statistic, allowed to use of a fixed-effects modelling for meta-analysis. Nine RCTs among 2337, including 826 patients (442 treated with probiotics/symbiotic and 384 with placebo) were analyzed. Eight were double-blind RCTs, and six enrolled ulcerative colitis (UC) patients. Although the risk for the overall side effects (RR 1.35, 95%CI 0.93-1.94; I2 = 25%) and for gastrointestinal symptoms (RR 1.78, 95%CI 0.99-3.20; I2 = 20%) was higher in IBD patients taking probiotics than in those exposed to placebo, statistical significance was achieved only for abdominal pain (RR 2.59, 95%CI 1.28-5.22; I2 = 40%). In conclusion, despite the small number of RCTs and the variety of probiotic used and schedule across studies, these findings highlight the level of research effort still required to identify the most appropriate use of probiotics in IBD.

Use of probiotics in medical devices applied to some common pathologies.

Probiotics, defined as "living microorganisms that, whether ingested in useful amount, may have beneficial effects on human body", are widely used in various products for human use, such as dietary supplements, medical devices and pharmaceutical products. The European Directive on medical devices (MDs) (DDM 93/42), also includes those MDs containing live microorganisms, particularly probiotics, that may have various destinations of use, including that of assisting the therapy of several human pathologies. In this brief note we analyzed the use of probiotics in MDs and how probiotics administration could represent one of the new frontiers of scientific research on the prevention and treatment of various diseases. We'll analyze the literature on probiotics based MDs, to review their major targets in the therapy of some of the most common human pathologies: bacterial vaginosis and vaginitis, atopic dermatitis, infantile colic, obesity, type 2 diabetes, and pharyngotonsillitis.

Dealing with the remaining controversies of probiotic safety.

A clear safety profile of probiotics in clinical practice is essential in decision-making for all stakeholders and regulators. Probiotics have been investigated in different target populations, conditions and age groups. This also includes the use of probiotics in critically ill patients. Despite promising results reported with the use of probiotics and synbiotics, there is still a lively discussion regarding the proper and safe use of probiotics among physicians, researchers and regulators. This doubt and debate was sparked by the high incidence in mortality reported in a study with critically ill patients. Whereas no causal relationship has been established since, safety of probiotic has been questioned. In response, an overwhelming body of evidence suggesting that probiotics are safe has been compiled. Moreover, data indicates that probiotics reduce the number of adverse events compared to the control. However, due to a lack of standardised safety reporting in clinical studies, a strong evidence base on probiotic safety remains to be established. Here, we will discuss: (1) the rationale for using probiotics in the critically ill; (2) what happened during the Dutch Pancreatitis trial; (3) what are the known safety risks of probiotics based on the available data; and finally (4) how standardisation in safety reporting can drive probiotic innovation. Building a strong safety profile for probiotic strains will solidify its use in individuals that can benefit the most from microbial modulation.

Effect of synbiotic pomegranate juice on glycemic, sex hormone profile and anthropometric indices in PCOS: A randomized, triple blind, controlled trial.

BACKGROUND AND AIMS: Polycystic Ovarian Syndrome is a common reproductive, endocrine, and metabolic disease in women. Pomegranate juice, known as a rich source of phytochemicals with high antioxidant activity, enriched with probiotic may improve PCOS. METHODS AND RESULTS: A randomized, controlled, triple-blinded, parallel trial study was performed in PCOS patients (n = 92). Three treatment groups (23 patients each) received 2 L of synbiotic pomegranate juice (SPJ), pomegranate juice (PJ), and synbiotic beverage (SB) weekly. The control group (23 patients) received 2 L of placebo beverage weekly. Primary outcome was any change in insulin resistance and secondary outcomes were fasting blood sugar (FBS), insulin sensitivity, testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), body mass index (BMI), waist and hip circumference, from baseline to the end of the trial. At the end of the study, 86 patients were analyzed. There was significant change in insulin resistance in the SPJ and SB groups. Insulin sensitivity increased significantly in the SPJ and SB groups. Insulin also changed significantly in the SPJ and SB groups. BMI, weight and waist circumference decreased significantly in the SPJ and SB groups. Testosterone level also decreased significantly in the SPJ and SB groups. There was no significant change in FPG, LH and FSH in any of the groups. CONCLUSION: SPJ in the form of a new beverage can improve insulin resistance, insulin, testosterone level, BMI, weight and waist circumference in PCOS. This trial was registered in Iranian Registry of Clinical Trials, with number: 25272.

Prebiotic, Probiotic, and Synbiotic Supplementation in Chronic Kidney Disease: A Systematic Review and Meta-analysis.

OBJECTIVE: Gut dysbiosis has been implicated in the pathogenesis of chronic kidney disease (CKD). Restoring gut microbiota with prebiotic, probiotic, and synbiotic supplementation has emerged as a potential therapeutic intervention but has not been systematically evaluated in the CKD population. DESIGN AND METHODS: This is a systematic review. A structured search of MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and the International Clinical Trials Register Search Portal was conducted for articles published since inception until July 2017. Included studies were randomized controlled trials investigating the effects of prebiotic, probiotic, and/or synbiotic supplementation (>1 week) on uremic toxins, microbiota profile, and clinical and patient-centered outcomes in adults and children with CKD. RESULTS: Sixteen studies investigating 645 adults met the inclusion criteria; 5 investigated prebiotics, 6 probiotics, and 5 synbiotics. The quality of the studies (Grades of Recommendation, Assessment, Development and Evaluation) ranged from moderate to very low. Prebiotic, probiotic, and synbiotic supplementation may have led to little or no difference in serum urea (9 studies, 345 participants: mean difference [MD] -0.30 mmol/L, 95% confidence interval [CI] -2.20 to 1.61, P = .76, I2 = 53%), indoxyl sulfate (4 studies, 144 participants: MD -0.02 mg/dL, 95% CI -0.09 to 0.05, P = .61, I2 = 0%), and p-cresyl sulfate (4 studies, 144 participants: MD -0.13 mg/dL, 95% CI -0.41 to 0.15, P = .35, I2 = 0%). Prebiotic supplementation may have slightly reduced serum urea concentration (4 studies, 105 participants: MD -2.23 mmol/L, 95% CI -3.83 to -0.64, P = .006, I2 = 11). Of the 2 studies investigating microbiota changes, synbiotic interventions significantly increased Bifidobacterium. Supplement effects on clinical outcomes were uncertain. CONCLUSIONS: There is limited evidence to support the use of prebiotics, probiotics, and/or synbiotics in CKD management.

Harms Reporting in Randomized Controlled Trials of Interventions Aimed at Modifying Microbiota: A Systematic Review.

Background: Probiotics, prebiotics, and synbiotics are used increasingly, although the safety and potential harms of these interventions are poorly understood. Purpose: To examine how harms-related information is reported in publications of randomized controlled trials (RCTs) of probiotics, prebiotics, and synbiotics. Data Sources: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science (without language restrictions) from 1 January 2015 to 20 March 2018. Study Selection: RCTs assessing the safety or efficacy of at least 1 intervention involving probiotics, prebiotics, or synbiotics alone or in combination with another intervention compared with any control (such as a placebo or an antibiotic) for any clinical condition. Data Extraction: 4 reviewers independently assessed study characteristics, the reporting of harms, and the presentation of safety results. Data Synthesis: Of 384 trials conducted in healthy volunteers (n = 136) or patients with any of several medical conditions (n = 248), 339 (88%) were published in specialty journals. Trials most often evaluated probiotics (n = 265 [69%]). Studies in persons with medical conditions enrolled outpatients (n = 195) and high-risk patients (n = 53). No harms-related data were reported for 106 trials (28%), safety results were not reported for 142 (37%), and the number of serious adverse events (SAEs) per study group was not given for 309 (80%). Of 242 studies mentioning harms-related results, 37% (n = 89) used only generic statements to describe AEs and 16% (n = 38) used inadequate metrics. Overall, 375 trials (98%) did not give a definition for AEs or SAEs, the number of participant withdrawals due to harms, or the number of AEs and SAEs per study group with denominators. Limitation: Journal publication processes may have affected the completeness of reporting; only English-language publications were examined. Conclusion: Harms reporting in published reports of RCTs assessing probiotics, prebiotics, and synbiotics often is lacking or inadequate. We cannot broadly conclude that these interventions are safe without reporting safety data. Primary Funding Source: No specific funding.

Probiotics, prebiotics and synbiotics for chronic kidney disease: protocol for a systematic review and meta-analysis.

INTRODUCTION: There is a growing interest in probiotic, prebiotic and synbiotic supplements for patients with chronic kidney disease (CKD). However, a systematic review and evaluation is lacking. The purpose of the present study is to assess the efficacy and safety of probiotics, prebiotics and synbiotics for non-dialysis or non-renal transplant patients with CKD. METHODS AND ANALYSIS: An extensive literature search will be undertaken to identify potentially eligible studies from electronic databases including PubMed (1946 to present), EMBASE (1974 to present), Web of Science (1900 to present) and the Cochrane Central Register of Controlled Trials (CENTRAL, all years). No language restriction will be applied to the search. Both parallel and crossover randomised controlled trials will be included. The risk of bias of each included study will be assessed using the Cochrane Risk of Bias Tool. The primary outcome measures are uraemic toxins. Secondary outcomes include kidney function, adverse cardiovascular events, all-cause mortality, cause-specific death, progression to end-stage kidney disease, quality of life, gastrointestinal function and adverse events. Data will be synthesised using appropriate statistical methods. The quality of evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: No ethical approval is required as no primary data will be collected. We will publish findings from this systematic review in a peer-reviewed scientific journal, and the data set will be made freely available. PROSPERO REGISTRATION NUMBER: CRD42017079177.

Effects of Synbiotics among Constipated Adults in Serdang, Selangor, Malaysia-A Randomised, Double-Blind, Placebo-Controlled Trial.

Synbiotics approach complementarily and synergistically toward the balance of gastrointestinal microbiota and improvement in bowel functions. A randomised, double-blind, placebo-controlled study was conducted to examine the effects of a synbiotics supplement among constipated adults. A total of 85 constipated adults, diagnosed by Rome III criteria for functional constipation were randomised to receive either synbiotics (n = 43) or placebo (n = 42) once daily (2.5 g) in the morning for 12 weeks. Eight times of follow-up was conducted every fortnightly with treatment response based on a questionnaire that included a record of evacuation (stool frequency, stool type according to Bristol Stool Form Scale), Patients Assessment on Constipation Symptoms (PAC-SYM), and Patients Assessment on Constipation Quality of Life (PAC-QOL). There were no significant differences in stool evacuation, but defecation frequency and stool type in treatment group were improved tremendously than in placebo group. While the treatment group was reported to have higher reduction in severity of functional constipation symptoms, the differences were not statistically significant. Dietary supplementation of synbiotics in this study suggested that the combination of probiotics and prebiotics improved the functional constipation symptoms and quality of life although not significant. This was due to the high placebo effect which synbiotics failed to demonstrate benefit over the controls.

Effects of Products Containing Bacillus subtilis var. natto on Healthy Subjects with Neck and Shoulder Stiffness, a Double-Blind, Placebo-Controlled, Randomized Crossover Study.

Neck and shoulder stiffness is a typical subjective symptom in developed countries. This stiffness is caused by factors such as muscle tension and poor blood flow, leading to reduce work efficiency and diminish QOL. NKCP®, a natto-derived dietary food supplement whose main component is bacillopeptidase F, has antithrombotic, fibrinolytic, and blood viscosity-lowering effects. Here, we investigated the effect of NKCP® on neck and shoulder stiffness in a double-blind placebo-controlled randomized crossover study. Thirty subjects with neck and shoulder stiffness were randomly divided into 2 groups and ingested 250 mg of NKCP® or placebo daily for 4 weeks. Headache score significantly improved in the NKCP® group compared to the placebo group. Moreover, NKCP® significantly improved the score of visual analogue scale for neck and shoulder stiffness and pain, reduced muscle stiffness of the neck, and increased the skin surface temperature of neck and shoulders, compared to before ingestion. No adverse effects were observed during this study. These results suggest that NKCP® may alleviate headaches and chronic neck and shoulder stiffness and pain.

Immune-Mediated Mechanisms of Action of Probiotics and Synbiotics in Treating Pediatric Intestinal Diseases.

The pediatric population is continually at risk of developing infectious and inflammatory diseases. The treatment for infections, particularly gastrointestinal conditions, focuses on oral or intravenous rehydration, nutritional support and, in certain case, antibiotics. Over the past decade, the probiotics and synbiotics administration for the prevention and treatment of different acute and chronic infectious diseases has dramatically increased. Probiotic microorganisms are primarily used as treatments because they can stimulate changes in the intestinal microbial ecosystem and improve the immunological status of the host. The beneficial impact of probiotics is mediated by different mechanisms. These mechanisms include the probiotics' capacity to increase the intestinal barrier function, to prevent bacterial transferation and to modulate inflammation through immune receptor cascade signaling, as well as their ability to regulate the expression of selected host intestinal genes. Nevertheless, with respect to pediatric intestinal diseases, information pertaining to these key mechanisms of action is scarce, particularly for immune-mediated mechanisms of action. In the present work, we review the biochemical and molecular mechanisms of action of probiotics and synbiotics that affect the immune system.

The effects of probiotic and synbiotic supplementation on metabolic syndrome indices in adults at risk of type 2 diabetes: study protocol for a randomized controlled trial.

BACKGROUND: The incidence of type 2 diabetes, cardiovascular diseases, and obesity has been rising dramatically; however, their pathogenesis is particularly intriguing. Recently, dysbiosis of the intestinal microbiota has emerged as a new candidate that may be linked to metabolic diseases. We hypothesize that selective modulation of the intestinal microbiota by probiotic or synbiotic supplementation may improve metabolic dysfunction and prevent diabetes in prediabetics. In this study, a synthesis and study of synbiotics will be carried out for the first time in Iran. METHODS/DESIGN: In a randomized triple-blind controlled clinical trial, 120 adults with impaired glucose tolerance based on the inclusion criteria will be selected by a simple random sampling method and will be randomly allocated to 6 months of 6 g/d probiotic, synbiotic or placebo. The fecal abundance of bacteria, blood pressure, height, weight, and waist and hip circumferences will be measured at baseline and following treatment. Also, plasma lipid profiles, HbA1C, fasting plasma glucose, and insulin levels, will be measured and insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) will be calculated at baseline and will be repeated at months 3, 6, 12, and 18. The data will be compared within and between groups using statistical methods. DISCUSSION: The results of this trial could contribute to the evidence-based clinical guidelines that address gut microbiota manipulation to maximize health benefits in prevention and management of metabolic syndrome in prediabetes. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT201511032321N2 . Registered on 27 February 2016.

Effects of infant formula supplemented with prebiotics compared with synbiotics on growth up to the age of 12 mo: a randomized controlled trial.

BACKGROUND: Growth is an essential outcome measure for evaluating the safety of infant formulas (IF). We investigated the effects of consumption of IF supplemented with prebiotics (fructooligosaccharides, FOS, and galactooligosaccharides, GOS) compared with synbiotics (FOS/GOS and Lactobacillus paracasei ssp. paracasei strain F19) on the growth of healthy infants. METHODS: 182 full-term infants who were weaned completely from breast milk to IF at 28 d of age were randomly assigned to receive prebiotic- or synbiotic-supplemented, otherwise identical, IF until 6 mo of age (intervention period). RESULTS: A total of 146 (80%) infants were included in the intention-to-treat analysis at 6 mo. Anthropometric parameters were similar in the two groups during the intervention and follow-up period until 12 mo of age. Compared with the prebiotic group, a significant reduction in the cumulative incidence of lower respiratory tract infections was found in the synbiotic group; however, the confidence interval of the estimate was wide, resulting in uncertainty. CONCLUSION: The lack of a significant difference between the formula-fed groups in growth, or the occurrence of serious adverse events, supports the safety of using IF supplemented with synbiotics. Further studies are needed to evaluate the effects of such formula on lower-respiratory tract infections.