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Effect of probiotics or prebiotics on thyroid function: A meta-analysis of eight randomized controlled trials.
Shu, Q, Kang, C, Li, J, Hou, Z, Xiong, M, Wang, X, Peng, H
PloS one. 2024;19(1):e0296733
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The gut microbiome is thought to play a role in thyroid disorders, mediated by regulating iodine uptake, degradation and enterohepatic cycling of thyroid hormones, and differences in microbiome composition between patients with thyroid disorders and healthy individuals have been observed. The aim of this systematic review and meta-analysis was to evaluate the effect of pro-, pre- and synbiotics on thyroid function (thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) and thyroid stimulating hormone receptor antibody (TRAb)) in patients with and without thyroid disorders. 8 randomised controlled trials including 367 participants were included in the review and meta-analysis. Neither pro-, pre- nor synbiotics had a significant effect on TSH, fT4 or fT3 but pre- and probiotics lead to a significant reduction in TRAb in patients with Graves’ disease.
Abstract
BACKGROUND Microbiome-directed therapies are increasingly utilized to optimize thyroid function in both healthy individuals and those with thyroid disorders. However, recent doubts have been raised regarding the efficacy of probiotics, prebiotics, and synbiotics in improving thyroid function. This systematic review aimed to investigate the potential relationship between probiotics/prebiotics and thyroid function by analyzing the impact on thyroid hormone levels. METHODS We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials that investigated the effects of probiotics, prebiotics, and synbiotics on free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid stimulating hormone receptor antibody (TRAb) levels. We searched for articles from PubMed, Scopus, Web of Science, and Embase up until April 1st, 2023, without any language restriction. Quantitative data analysis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval as summary statistics. The methods and results were reported according to the PRISMA2020 statement. RESULTS A total of eight articles were included in this review. The meta-analysis showed no significant alterations in TSH (SMD: -0.01, 95% CI: -0.21, 0.20, P = 0.93; I2: 0.00%), fT4 (SMD: 0.04, 95% CI: -0.29, 0.21, P = 0.73; I2: 0.00%) or fT3 (SMD: 0.45, 95% CI: -0.14, 1.03, P = 0.43; I2: 78.00%), while a significant reduction in TRAb levels was observed (SMD: -0.85, 95% CI: -1.54, -0.15, P = 0.02; I2: 18.00%) following probiotics/prebiotics supplementation. No indication of publication bias was found. CONCLUSIONS Probiotics/prebiotics supplementation does not influence thyroid hormone levels, but may modestly reduce TRAb levels in patients with Graves' disease.
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Effect of supplementation with probiotics or synbiotics on cardiovascular risk factors in patients with metabolic syndrome: a systematic review and meta-analysis of randomized clinical trials.
Chen, T, Wang, J, Liu, Z, Gao, F
Frontiers in endocrinology. 2023;14:1282699
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Metabolic syndrome (metS) is characterised by insulin resistance, dyslipidaemia, central obesity and/or high blood pressure and is a significant risk factor for cardiovascular disease and type 2 diabetes mellitus. MetS is associated with an imbalanced microbiome and some but not all studies have shown benefits of supplementation with probiotics. The aim of this systematic review and meta-analysis of randomised controlled trials was to evaluate the effects of pro- or synbiotics on cardiovascular risk factors (body mass index, LDL cholesterol, fasting blood glucose and systolic blood pressure) in patients with metS. 11 studies were included in the review of which 7 were judged to have a low risk of bias, whilst risk of bias was unclear in 4 articles. The meta-analysis found that pro- or synbiotics have a positive effect on body mass index, LDL cholesterol and fasting blood glucose but not on systolic blood pressure. Subgroup analysis of pro- and synbiotics separately also found no effects on systolic blood pressure.
Abstract
PURPOSE The effectiveness of probiotics or synbiotics in adults with metabolic syndromes (MetS) remains controversial, this meta-analysis will further analyze the effects of probiotics or synbiotics on cardiovascular factors in adults with MetS. METHODS We searched Web of Science, PubMed, Embase, Cochrane Library and other databases for randomized controlled trials (RCTs) on the effects of probiotics or synbiotics on MetS in adults up to July 2023, and used RevMan 5.4.0 software for statistical analysis. RESULTS This analysis included eleven RCTs (n = 608 participants), and the results showed that compared with the control group, supplementation with probiotics or synbiotics reduced body mass index (weighted mean difference, WMD = -0.83, 95% CI = [-1.21, -0.44], P <0.0001, n = 9), low-density lipoprotein (LDL-c) (standard mean difference, SMD = -0.24, 95% CI = [-0.41, -0.08], P = 0.004, n = 10), fasting blood glucose (FBG)(SMD = -0.17, 95% CI = [-0.33, -0.01], P = 0.03, n = 11), but had no beneficial effect on systolic blood pressure (SBP) (WMD = 1.24, 95% CI = [-2.06, 4.54], P = 0.46, n = 8) in MetS patients. CONCLUSION Supplementation with probiotics or synbiotics can reduce BMI, LDL-c, FBG in patients with MetS, but our findings did not demonstrate a favorable effect on reducing SBP. Future studies with larger samples and longer intervention periods are needed.
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Effects of Vitamin D Supplementation During Pregnancy on Birth Size: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Maugeri, A, Barchitta, M, Blanco, I, Agodi, A
Nutrients. 2019;11(2)
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Vitamin D deficiency may affect mother and neonatal outcomes, increasing the risk of pregnancy complications, preterm birth, low birth weight (LBW), small for gestational age (SGA), and poor offspring health. This systematic review and meta-analysis evaluates the effects of oral vitamin D supplementation during pregnancy on foetal growth and incidence of LBW and SGA births. 13 randomised controlled trials (RCTs), published between 1980 and 2016, were included in the meta-analysis, including in total 2016 newborns (1184 from mothers in the intervention groups and 832 from controls). Dosages ranged from 200-4000 IU for daily intakes and 35000 IU to 600000 IU for single or intermittent administration. Whilst there was no evidence for publication bias (e.g. an over-reporting of positive outcomes), overall, the quality of the reviewed studies varied from very low (head circumference) to moderate (birth weight, birth length, LBW, and SGA). All studies evaluating the effect of vitamin D supplementation on blood 25-hydroxyvitamin D (OHD) levels showed that intervention significantly increased 25-OHD concentration in both mothers and infants. The meta-analysis showed that vitamin D supplementation significantly increased birth weight and length, independent of dosage and whether vitamin D was administered daily or in single/intermittent high dosages. Head circumference was increased in a non-dose dependent way with daily but not with single/intermittent vitamin D supplementation. Effects on all three parameters were seen when vitamin D was supplemented alone, but not in combination with other nutrients. Both, risk of LBW and SGA, were also significantly reduced with vitamin D supplementation.
Abstract
During pregnancy, vitamin D supplementation may be a feasible strategy to help prevent low birthweight (LBW) and small for gestational age (SGA) births. However, evidence from randomized controlled trials (RCTs) is inconclusive, probably due to heterogeneity in study design and type of intervention. A systematic literature search in the PubMed-Medline, EMBASE, and Cochrane Central Register of Controlled Trials databases was carried out to evaluate the effects of oral vitamin D supplementation during pregnancy on birthweight, birth length, head circumference, LBW, and SGA. The fixed-effects or random-effects models were used to calculate mean difference (MD), risk ratio (RR), and 95% Confidence Interval (CI). On a total of 13 RCTs, maternal vitamin D supplementation had a positive effect on birthweight (12 RCTs; MD = 103.17 g, 95% CI 62.29⁻144.04 g), length (6 RCTs; MD = 0.22 cm, 95% CI 0.11⁻0.33 cm), and head circumference (6 RCTs; MD:0.19 cm, 95% CI 0.13⁻0.24 cm). In line with these findings, we also demonstrated that maternal vitamin D supplementation reduced the risk of LBW (3 RCTs; RR = 0.40, 95% CI 0.22⁻0.74) and SGA (5 RCTS; RR = 0.69, 95% CI 0.51⁻0.92). The present systematic review and meta-analysis confirmed the well-established effect of maternal vitamin D supplementation on birth size. However, further research is required to better define risks and benefits associated with such interventions and the potential implications for public health.
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Effectiveness of Vitamin D Supplementation in the Management of Multiple Sclerosis: A Systematic Review.
Berezowska, M, Coe, S, Dawes, H
International journal of molecular sciences. 2019;20(6)
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Epidemiological research shows that Vitamin D status is associated with reduced activity and progression of disease in multiple sclerosis (MS). This review assessed the evidence from ten double-blind randomised controlled trials, including a total of 627 adults with relapsing remitting MS (RRMS), for the clinical effectiveness of vitamin D supplementation compared to placebo in disease and symptom management. The results from the reviewed studies on disease progression and immunological blood parameters were mixed. Where benefits of vitamin D supplementation were seen this tended to be in those groups where vitamin D levels were low at the start of the study. Those studies evaluating the safety and tolerability of vitamin D reported no serious adverse events. The authors conclude that baseline serum vitamin D levels may be a predictor of improvements in RRMS with vitamin D supplementation, and that further research should include baseline vitamin D as part of the assessment.
Abstract
OBJECTIVE to examine the extent of effect vitamin D in Multiple Sclerosis (MS) on pathology and symptoms. METHODS A literature search was performed in November 2018 (CRD42018103615). Eligibility criteria: randomised control trials in English from 2012 to 2018; a clinical diagnosis of MS; interventions containing vitamin D supplementation (vitamin D3 or calcitriol) in disease activity compared to a control/placebo; improvement in: serum 25(OH)D, relapse rates, disability status by Expanded Disability Status Scale (EDSS) scores, cytokine profile, quality of life, mobility, T2 lesion load and new T2 or T1 Gd enhancing lesions, safety and adverse effects. Risk of bias was evaluated. RESULTS Ten studies were selected. The study size ranged from 40 to 94 people. All studies evaluated the use of vitamin D supplementation (ranging from 10 to 98,000 IU), comparing to a placebo or low dose vitamin D. The duration of the intervention ranged from 12 to 96 weeks. One trial found a significant effect on EDSS score, three demonstrated a significant change in serum cytokines level, one found benefits to current enhancing lesions and three studies evaluating the safety and tolerability of vitamin D reported no serious adverse events. Disease measures improved to a greater extent overall in those with lower baseline serum 25(OH)D levels. CONCLUSIONS As shown in 3 out of 10 studies, improvement in disease measures may be more apparent in those with lower baseline vitamin D levels.
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Impact of Fecal Microbiota Transplantation on Obesity and Metabolic Syndrome-A Systematic Review.
Zhang, Z, Mocanu, V, Cai, C, Dang, J, Slater, L, Deehan, EC, Walter, J, Madsen, KL
Nutrients. 2019;11(10)
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Fecal microbiota transplantation (FMT) is a relatively new field of scientific exploration where patients receive faeces from a healthy donor to help repopulate their intestinal tract with healthful bacteria. The gut microbiome is an ecosystem of an estimated 10~100 trillion microorganisms and there is increasing research on the important role these bacteria play in supporting our health and weight. This study reviews all trials involving faecal transports in patients with either clinical obesity or Metabolic syndrome to see if it helped improve weight, bmi or other metabolic parameters. Three studies with 76 male patients were included in this review and the results showed that FMT recipients had improved insulin sensitivity and reduced HbA1c glucose levels after 6 weeks, but these improvements were short-term only. There were no differences in bmi, cholesterol, markers and fasting glucose levels. The conclusion is that whilst FMT may confer benefits there is still much to understand about the fecal microbial preparation, dosing, and method of delivery, as well as the host patient’s response.
Abstract
Fecal microbiota transplantation (FMT) is a gut microbial-modulation strategy that has been investigated for the treatment of a variety of human diseases, including obesity-associated metabolic disorders. This study appraises current literature and provides an overview of the effectiveness and limitations of FMT as a potential therapeutic strategy for obesity and metabolic syndrome (MS). Five electronic databases and two gray literature sources were searched up to 10 December 2018. All interventional and observational studies that contained information on the relevant population (adult patients with obesity and MS), intervention (receiving allogeneic FMT) and outcomes (metabolic parameters) were eligible. From 1096 unique citations, three randomized placebo-controlled studies (76 patients with obesity and MS, body mass index = 34.8 ± 4.1 kg/m2, fasting plasma glucose = 5.8 ± 0.7 mmol/L) were included for review. Studies reported mixed results with regards to improvement in metabolic parameters. Two studies reported improved peripheral insulin sensitivity (rate of glucose disappearance, RD) at 6 weeks in patients receiving donor FMT versus patients receiving the placebo control. In addition, one study observed lower HbA1c levels in FMT patients at 6 weeks. No differences in fasting plasma glucose, hepatic insulin sensitivity, body mass index (BMI), or cholesterol markers were observed between two groups across all included studies. While promising, the influence of FMT on long-term clinical endpoints needs to be further explored. Future studies are also required to better understand the mechanisms through which changes in gut microbial ecology and engraftment of microbiota affect metabolic outcomes for patients with obesity and MS. In addition, further research is needed to better define the optimal fecal microbial preparation, dosing, and method of delivery.
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Probiotic monotherapy and Helicobacter pylori eradication: A systematic review with pooled-data analysis.
Losurdo, G, Cubisino, R, Barone, M, Principi, M, Leandro, G, Ierardi, E, Di Leo, A
World journal of gastroenterology. 2018;24(1):139-149
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Helicobacter pylori (H-pylori) is a parasite that resides in the human stomach and is associated with the development of stomach ulcers, amongst other conditions. Conventional treatment relies on a combination of antibiotics and stomach acid suppressants, however failure rates for standard treatments have been rising and alternatives are required. Probiotics (live bacteria that provide health benefits to their host) have been used alongside antibiotic treatment for H-pylori in some cases to reduce medication side effects. This systematic review of 11 studies including 517 H-pylori infected patients, aimed to assess the effects of probiotic therapy alone on H-pylori status. The study found that the eradication rate of H-pylori with a variety of probiotic strains was 12-16%, compared to a 0% success rate in the placebo groups. Clinically, this rate is low, however the authors conclude that probiotics may have a role to play in a multi-therapy approach for the eradication of H-pylori.
Abstract
AIM: To define probiotic monotherapy effect on Helicobacter pylori (H. pylori) status by performing a systematic review. METHODS Methods of analysis and inclusion criteria were based on PRISMA recommendations. Relevant publications were identified by searching PubMed, MEDLINE, Science Direct, and EMBASE. The end-point was to estimate eradication rate and urea breath test delta value before and after probiotic monotherapy across all studies and, overall, with a pooled data analysis. Adverse events of probiotic therapy were evaluated. The data were expressed as proportions/percentages, and 95%CIs were calculated. For continuous variables, we evaluated the weighted mean difference. Odd ratios (ORs) were calculated according to the Peto method for the comparison of eradication rates between probiotics and placebo. RESULTS Eleven studies were selected. Probiotics eradicated H. pylori in 50 out of 403 cases. The mean weighted eradication rate was 14% (95%CI: 2%-25%, P = 0.02). Lactobacilli eradicated the bacterium in 30 out of 235 patients, with a mean weighted rate of 16% (95%CI: 1%-31%). Saccharomyces boulardii achieved eradication in 6 out of 63 patients, with a pooled eradication rate of 12% (95%CI: 0%-29%). Multistrain combinations were effective in 14 out of 105 patients, with a pooled eradication rate of 14% (95%CI: 0%-43%). In the comparison of probiotics vs placebo, we found an OR of 7.91 in favor of probiotics (95%CI: 2.97-21.05, P < 0.001). Probiotics induced a mean reduction in delta values higher than placebo (8.61% with a 95%CI: 5.88-11.34, vs 0.19% for placebo, P < 0.001). Finally, no significant difference in adverse events was found between probiotics and placebo (OR = 1, 95%CI: 0.06-18.08). CONCLUSION Probiotics alone show a minimal effect on H. pylori clearance, thus suggesting a likely direct role.
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The Effect of Bifidobacterium animalis ssp. lactis HN019 on Cellular Immune Function in Healthy Elderly Subjects: Systematic Review and Meta-Analysis.
Miller, LE, Lehtoranta, L, Lehtinen, MJ
Nutrients. 2017;9(3)
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Elderly individuals are more susceptible to infections and cancer, due to lowered immune system function. The gut bacteria play a key role in human immune system function and there is an interest in a potential role for probiotics in strengthening the immune system through manipulation of the microbiome. This systematic review and meta-analysis of 4 randomised controlled trials aimed to examine the efficacy of Bifidobacterium animalis lactis HN019 on the cellular immune activity of healthy elderly adults age 60-70 years. The authors concluded that supplementation with this bacterial strain at a range of potencies for 3-6 weeks duration had a significant positive impact on the part of the immune system that is responsible for removing pathogens and cell debris (phagocytosis) and a lesser but nevertheless significant impact on natural killer cells responsible for tumour destruction.
Abstract
Elderly people have increased susceptibility to infections and cancer that are associated with decline in cellular immune function. The objective of this work was to determine the efficacy of Bifidobacterium (B.) animalis ssp. lactis HN019 (HN019) supplementation on cellular immune activity in healthy elderly subjects. We conducted a systematic review of Medline and Embase for controlled trials that reported polymorphonuclear (PMN) cell phagocytic capacity or natural killer (NK) cell tumoricidal activity following B. lactis HN019 consumption in the elderly. A random effects meta-analysis was performed with standardized mean difference (SMD) and 95% confidence interval between probiotic and control groups for each outcome. A total of four clinical trials were included in this analysis. B. lactis HN019 supplementation was highly efficacious in increasing PMN phagocytic capacity with an SMD of 0.74 (95% confidence interval: 0.38 to 1.11, p < 0.001) and moderately efficacious in increasing NK cell tumoricidal activity with an SMD of 0.43 (95% confidence interval: 0.08 to 0.78, p = 0.02). The main limitations of this research were the small number of included studies, short-term follow-up, and assessment of a single probiotic strain. In conclusion, daily consumption of B. lactis HN019 enhances NK cell and PMN function in healthy elderly adults.
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Impact of Probiotic Administration on Serum C-Reactive Protein Concentrations: Systematic Review and Meta-Analysis of Randomized Control Trials.
Mazidi, M, Rezaie, P, Ferns, GA, Vatanparast, H
Nutrients. 2017;9(1)
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C-reactive protein (CRP) is a blood marker of inflammation and is frequently elevated in chronic conditions such as heart disease, obesity and Type 2 diabetes. Some strains of probiotics (bacteria that exert health benefits) are thought to act as anti-inflammatory agents through various mechanisms. This systematic review and meta-analysis of 20 randomised controlled trials (RCTs) aimed to investigate the effects of probiotic supplementation on CRP levels as one measure of inflammation. The meta-analysis indicates that probiotic supplementation with various strains of bacteria has a significant impact on serum CRP levels, with a weighted mean difference of -1.35mg/l. Whilst positive impacts were also seen for interleukin-10 and tumour necrosis factor-alpha (other markers of inflammation) with probiotics, these did not reach significance. The authors of this study point out that the results need to be interpreted with caution owing to the wide variety of study types, study size, probiotic strains and health outcomes measured in the included RCTs. However, Nutrition Practitioners working with clients with raised CRP levels may want to investigate the use of certain probiotic strains as part of an anti-inflammatory protocol.
Abstract
We conducted this systematic review and meta-analysis of prospective studies to determine the effect of probiotic administration on serum C-reactive protein (CRP) concentrations. We searched PubMed-Medline, Web of Science, the Cochrane, and Google Scholar databases (until May 2016) to identify prospective studies evaluating the impact of probiotic administration on CRP. We used a random effects models and generic inverse variance methods to synthesize quantitative data, followed by a leave-one-out method for sensitivity analysis. The systematic review registration number was: CRD42016039457. From a total of 425 entries identified via searches, 20 studies were included in the final analysis. The meta-analysis indicated a significant reduction in serum CRP following probiotic administration with a weighted mean difference (WMD) of -1.35 mg/L, (95% confidence interval (CI) -2.15 to -0.55, I² 65.1%). The WMDs for interleukin 10 (IL10) was -1.65 pg/dL, (95% CI -3.45 to 0.14, I² 3.1%), and -0.45 pg/mL, (95% CI -1.38 to 0.48, I² 10.2%) for tumor necrosis factor alpha (TNF-α). These findings were robust in sensitivity analyses. This meta-analysis suggests that probiotic administration may significantly reduce serum CRP while having no significant effect on serum IL10 and TNF-α.