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1.
Meta-analysis of randomized controlled trials of the effects of probiotics on type 2 diabetes in adults.
Zhang, C, Jiang, J, Wang, C, Li, S, Yu, L, Tian, F, Zhao, J, Zhang, H, Chen, W, Zhai, Q
Clinical nutrition (Edinburgh, Scotland). 2022;(2):365-373
Abstract
BACKGROUND & AIMS Despite advancements in preventive medicine and pharmacotherapy, diabetes remains an overwhelming health problem. Evidence from randomized controlled trials (RCTs) suggests that probiotics may offer beneficial effects on glycemic control. Our objective was to perform a systematic review and meta-analysis of RCTs to quantify the effect of probiotic administration on glycemic homeostasis in type 2 diabetes. METHODS Medline, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for relevant trials published until October 12, 2021. RCTs that lasted ≥3 weeks and assessed the effects of probiotics on the markers of glycemic homeostasis in type 2 diabetes were included. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran's Q statistic and quantified using the I2 statistic. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. RESULTS A total of 33 eligible trial comparisons (n = 1927) were included in this meta-analysis. Our results revealed that compared with placebo, a median probiotic dose of ∼109 cfu/day significantly reduced the glycated hemoglobin (HbA1c) levels (MD: -0.19% [95% CI: -0.32, -0.07]; P = 0.003), fasting blood glucose levels (MD: -1.00 mmol/L [95% CI: -1.45, -0.56]; P < 0.0001), fasting insulin levels (MD: -5.73 pmol/L [95% CI: -12.17, 0.72]; P = 0.08), and HOMA-insulin resistance (IR) (MD: -1.00 [95% CI: -1.32, -0.68]; P < 0.00001). The certainty of evidence was graded low for HbA1c and fasting glucose, moderate for fasting insulin, and high for HOMA-IR. Probiotic supplements do not induce clinically significant reductions in HbA1c levels, but lead to marginally clinically significant reductions in fasting glucose and fasting insulin levels in patients with type 2 diabetes. Compared with single-strain and low-dose probiotics, multi-strain and high-dose probiotics have a greater beneficial effect on glycemic homeostasis. In addition, probiotic treatment may be more effective in patients with a high baseline body mass index and age.
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2.
Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Sanchez, P, Letarouilly, JG, Nguyen, Y, Sigaux, J, Barnetche, T, Czernichow, S, Flipo, RM, Sellam, J, Daïen, C
Nutrients. 2022;(2)
Abstract
BACKGROUND We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of probiotics supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis (SpA), or psoriatic arthritis). METHODS A systematic literature review and meta-analysis from RA and SpA randomized controlled trials were conducted searching for articles in MEDLINE/PubMed and abstracts from recent international rheumatology meetings. The control group was a placebo or another dietary intervention. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration tool and the Jadad scale. RESULTS The initial search yielded 173 articles. Of these, 13 studies were included in the qualitative synthesis, 8 concerning a total of 344 RA patients and 2 concerning a total of 197 SpA patients. Three meta-analyses were also analyzed. Probiotic strains and quantities used were different among trials (5 studies using Lactobacillus sp., 1 trial Bacillus coagulans and the others a mix of different probiotic strains). Time to assess response ranged from 8 weeks to one year. Two studies associated probiotic supplementation with a dietary intervention. Meta-analysis showed a statistically significant decrease of C-reactive protein (CRP) concentration (mean difference (MD)) -3.04 (95% CI -4.47, -1.62) mg/L, p < 0.001; I2 = 20%, n patients = 209) with probiotics in RA. However, after excluding high-risk-of-bias trials of meta-analysis, there was no difference between probiotics and placebo on DAS28 (standard MD -0.54; 95% CI -1.94 to 0.85, p = 0.45, I2 93%, n patients = 143). The two studies on SpA patients showed no efficacy of probiotics. CONCLUSIONS Probiotic supplementation might decrease RA activity with a moderate decrease effect on CRP, but lack of evidence and studies' heterogeneity do not allow us to propose them to patients with inflammatory arthritis to control their disease. Further RCTs are required in the future to determinate the efficacy of probiotics and the optimal administration design.
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3.
Effect of synbiotics and probiotics supplementation on autoimmune diseases: A systematic review and meta-analysis of clinical trials.
Askari, G, Ghavami, A, Shahdadian, F, Moravejolahkami, AR
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3221-3234
Abstract
BACKGROUND & AIMS Today synbiotics are considered as immunomodulatory agents. The current systematic review and meta-analysis investigated the effect of synbiotics and probiotics on inflammatory and oxidative stress markers in autoimmune disease. MATERIALS & METHODS The English literature search was performed using PubMed, Scopus, Web of Science, and the Central Cochrane Library through March 2020. Random effects models and generic inverse variance methods were used to synthesize quantitative data by STATA14. RESULTS From a total of 623 entries identified via searches, ten RCTs (n = 440; 216 as intervention, 224 as controls) were included. An additional eleven studies with same intervention and different markers were also explained systematically. The pooled effect size showed that Interleukin (IL)-6 (WMD = -7.79 pg/ml; 95% CI = -13.81, -1.77, P = 0.011), Tumor Necrosis Factor (TNF)-α (WMD = -1.05 pg/ml; 95% CI = -2.01, -0.10, P = 0.030), high sensitivity C-Reactive Protein (hs-CRP) (SMD = -0.58; 95% CI = -0.79, -0.37, P < 0.001), Malondialdehyde (MDA) (SMD = -0.36; 95% CI = -0.68, -0.04; P = 0.026), Homeostasis Model of Assessment-estimated Insulin Resistance (HOMA-IR) (WMD = -0.71; 95% CI = -1.05, -0.37, P < 0.001), and beta cell function (HOMA-β) (WMD = -15.18; 95% CI = -22.08, -8.28, P < 0.001) changed following probiotics (or synbiotics) supplementation. Also supplementation with doses more than 2 billion CFU could reduce IL-10 concentrations (WMD = -1.84; 95% CI = -2.23, 1.87; P < 0.001). Glutathione (GSH) and Total Antioxidant Capacity (TAC) levels did not influence by synbiotics and probiotics; insignificancy was remained after subgrouping for participants' age, study duration, and disease duration. CONCLUSION Our findings revealed that synbiotics and probiotics supplementation has significant effect on some inflammatory and oxidative stress markers; although, the number of trials was too small to powerful conclusion and further investigations may be needed.
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4.
Probiotics for Preventing Necrotizing Enterocolitis in Preterm Infants: A Network Meta-Analysis.
Beghetti, I, Panizza, D, Lenzi, J, Gori, D, Martini, S, Corvaglia, L, Aceti, A
Nutrients. 2021;(1)
Abstract
BACKGROUND Recent evidence supports a role of probiotics in preventing necrotizing enterocolitis (NEC) in preterm infants. METHODS A systematic review and network meta-analysis of randomized controlled trials (RCTs) on the role of probiotics in preventing NEC in preterm infants, focusing on the differential effect of type of feeding, was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A random-effects model was used; a subgroup analysis on exclusively human milk (HM)-fed infants vs. infants receiving formula (alone or with HM) was performed. RESULTS Fifty-one trials were included (10,664 infants, 29 probiotic interventions); 31 studies (19 different probiotic regimens) were suitable for subgroup analysis according to feeding. In the overall analysis, Lactobacillus acidophilus LB revealed the most promising effect for reducing NEC risk (odds ratio (OR), 0.03; 95% credible intervals (CrIs), 0.00-0.21). The subgroup analysis showed that Bifidobacterium lactis Bb-12/B94 was associated with a reduced risk of NEC stage ≥2 in both feeding type populations, with a discrepancy in the relative effect size in favour of exclusively HM-fed infants (OR 0.04; 95% CrIs <0.01-0.49 vs. OR 0.32; 95% CrIs 0.10-0.36). CONCLUSIONS B. lactis Bb-12/B94 could reduce NEC risk with a different size effect according to feeding type. Of note, most probiotic strains are evaluated in few trials and relatively small populations, and outcome data according to feeding type are not available for all RCTs. Further trials are needed to confirm the present findings.
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5.
Effects of Probiotics in Preterm Infants: A Network Meta-analysis.
Chi, C, Li, C, Buys, N, Wang, W, Yin, C, Sun, J
Pediatrics. 2021;(1)
Abstract
CONTEXT Probiotics have proven to be effective in promoting premature infants' health, but the optimal usage is unknown. OBJECTIVE To compare probiotic supplements for premature infants. DATA SOURCES We searched PubMed, Embase, Cochrane, and ProQuest from inception of these databases to June 1, 2020. STUDY SELECTION Randomized trials of probiotic supplement intervention for preterm infants were screened by 2 reviewers independently. The primary outcomes were mortality and the morbidity of necrotizing enterocolitis (NEC). Secondary outcomes were morbidity of sepsis, time to achieve full enteral feeding, and length of hospital stay. DATA EXTRACTION The data of primary and secondary outcomes were extracted by 2 reviewers and pooled with a random-effects model. RESULTS The meta-analysis included 45 trials with 12 320 participants. Bifidobacterium plus Lactobacillus was associated with lower rates of mortality (risk ratio 0.56; 95% credible interval 0.34-0.84) and NEC morbidity (0.47; 0.27-0.79) in comparison to the placebo; Lactobacillus plus prebiotic was associated with lower rates of NEC morbidity (0.06; 0.01-0.41) in comparison to the placebo; Bifidobacterium plus prebiotic had the highest probability of having the lowest rate of mortality (surface under the cumulative ranking curve 83.94%); and Lactobacillus plus prebiotic had the highest probability of having the lowest rate of NEC (surface under the cumulative ranking curve 95.62%). LIMITATIONS In few studies did authors report the data of infants with a lower birth weight or gestational age. CONCLUSIONS The efficacy of single probiotic supplements is limited, compared to combined use of probiotics. To achieve optimal effect on premature infant health, combined use of prebiotic and probiotic, especially Lactobacillus or Bifidobacterium, is recommended.
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6.
Probiotics as a therapeutic strategy in obesity and overweight: a systematic review.
Tomé-Castro, XM, Rodriguez-Arrastia, M, Cardona, D, Rueda-Ruzafa, L, Molina-Torres, G, Roman, P
Beneficial microbes. 2021;(1):5-15
Abstract
Obesity and overweight are two of the most health challenges with an increasing prevalence in recent years, in which several complications have been identified to have a high impact in patients' health conditions. In this vein, an increasing interest in the gut microbiota has emerged as a target for therapeutic strategies in obesity and overweight due to its direct relation with the aforementioned health conditions and complications. Thus, the aim of this study was to evaluate the efficacy of probiotics as a therapeutic strategy in the management of obesity and overweight. A systematic review of randomised controlled trials was carried out in 6 databases until May 2019 to assess the use of probiotics in obesity and overweight patients. The Jadad Scale was used to assess the quality of the clinical trials. Twenty-three clinical trials published between 2000 and 2019 met the inclusion criteria. The role of probiotics in reducing body mass index and weight as well as changing the visceral abdominal fat area, waist and hip circumference were shown in 14 of 23 trials (60.87%); 14 trials (60.87%) showed changes on patients' fatty acids and biomarkers; and 4 trials (17.39%) studied the role of the gut microbiota in obese and overweight patients. Some probiotics strains are shown to be effective in reducing body mass index and hip circumference. This review provides evidence of successful results in weight loss using probiotic groups.
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7.
Effects of probiotics and synbiotics on diarrhea in undernourished children: Systematic review with meta-analysis.
Kambale, RM, Nancy, FI, Ngaboyeka, GA, Kasengi, JB, Bindels, LB, Van der Linden, D
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3158-3169
Abstract
BACKGROUND Undernutrition predisposes children to a greater incidence and duration of diarrhea. No review and meta-analysis have yet been conducted to assess effectiveness of probiotics and synbiotics in undernourished children. AIMS To assess the effectiveness of probiotics and synbiotics on diarrhea in undernourished children. METHODS Randomized, double-blind, placebo-controlled trials evaluating the effects of probiotics and synbiotics on diarrhea in undernourished children were searched from 1990 to May 2020. Recommendations of the Cochrane Handbook and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement were followed. RESULTS The systematic review identified 15 trials with 6986 patients. The meta-analysis revealed that treatment with probiotic or synbiotic reduced significantly both the duration of diarrhea [Weighted mean difference (WMD) = -1.05 day, 95% CI (-1.98, -0.11)] and the hospital stay duration [Standard mean difference (SMD) = -2.87 days, 95% CI (-5.33, -0.42)], especially in specific patient subsets. In both groups, similar rates of vomiting and nutritional recovery were observed. No probiotics or synbiotics-related adverse effects were reported. Subgroup analyses showed that probiotic and synbiotic treatment were more effective in reducing risk of diarrhea in outpatients [Risk ratio (RR) = 0.86, 95%CI (0.75-0.98)]. CONCLUSION This meta-analysis supports the potential beneficial roles of probiotics and synbiotics on diarrhea in undernourished children.
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8.
Probiotic Supplementation for Promotion of Growth in Children: A Systematic Review and Meta-Analysis.
Catania, J, Pandit, NG, Ehrlich, JM, Zaman, M, Stone, E, Franceschi, C, Smith, A, Tanner-Smith, E, Zackular, JP, Bhutta, ZA, et al
Nutrients. 2021;(1)
Abstract
Probiotics are commonly prescribed to promote a healthy gut microbiome in children. Our objective was to investigate the effects of probiotic supplementation on growth outcomes in children 0-59 months of age. We conducted a systematic review and meta-analysis which included randomized controlled trials (RCTs) that administered probiotics to children aged 0-59 months, with growth outcomes as a result. We completed a random-effects meta-analysis and calculated a pooled standardized mean difference (SMD) or relative risk (RR) and reported with a 95% confidence interval (CI). We included 79 RCTs, 54 from high-income countries (HIC), and 25 from low- and middle-income countries (LMIC). LMIC data showed that probiotics may have a small effect on weight (SMD: 0.26, 95% CI: 0.11-0.42, grade-certainty = low) and height (SMD 0.16, 95% CI: 0.06-0.25, grade-certainty = moderate). HIC data did not show any clinically meaningful effect on weight (SMD: 0.01, 95% CI: -0.04-0.05, grade-certainty = moderate), or height (SMD: -0.01, 95% CI: -0.06-0.04, grade-certainty = moderate). There was no evidence that probiotics affected the risk of adverse events. We conclude that in otherwise healthy children aged 0-59 months, probiotics may have a small but heterogenous effect on weight and height in LMIC but not in children from HIC.
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9.
Lactoferrin Supplementation to Prevent Late-Onset Sepsis in Preterm Infants: A Meta-Analysis.
Razak, A, Hussain, A
American journal of perinatology. 2021;(3):283-290
Abstract
OBJECTIVE This study aimed to systematically review and meta-analyze the role of lactoferrin supplementation to prevent late-onset sepsis (LOS) in preterm infants. STUDY DESIGN Database search include PubMed, Web of Science, and Cochrane central for randomized clinical trial (RCTs). The Cochrane Grading of Recommendations Assessment, Development, and Evaluation methodology was used for summarizing the results. RESULTS Ten RCTs involving 3,679 infants were included. Lactoferrin supplementation with or without probiotics decreased all LOS (relative risk [RR]: 0.56; 95% confidence interval [CI]: 0.36-0.86; I 2 = 58%; 10 studies; 3,470 subjects; level of evidence [LOE]: low) significantly. Similarly, lactoferrin supplementation without probiotics decreased all LOS (RR: 0.43; 95% CI: 0.29-0.62; I 2 = 0%; 8 studies; 1,209 subjects; LOE: moderate) significantly. Lactoferrin supplementation did not significantly reduce necrotizing enterocolitis (RR: 0.62; 95% CI: 0.29-1.33; I 2 = 43%; 6 studies; 3,079 subjects; LOE: low), all-cause mortality (RR: 0.74; 95% CI: 0.36-1.53; I 2 = 53%; 8 studies; 3,395 subjects; LOE: very low), bronchopulmonary dysplasia (RR: 1; 95% CI: 0.90-1.13; I 2 = 0%; 4 studies; 2,570 subjects; LOE: moderate), and threshold retinopathy of prematurity eligible for surgical treatment (RR: 0.61; 95% CI: 0.25-1.51; I 2 = 74%; 2 studies; 2,481 subjects; LOE: very low). CONCLUSION Low to moderate quality evidence suggests that lactoferrin supplementation reduces LOS in preterm infants. Further research is needed to improve the certainty in the evidence.
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10.
Diet and Pre-Intervention Washout Modifies the Effects of Probiotics on Gestational Diabetes Mellitus: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Hasain, Z, Che Roos, NA, Rahmat, F, Mustapa, M, Raja Ali, RA, Mokhtar, NM
Nutrients. 2021;(9)
Abstract
Dynamic interactions among gestational diabetes mellitus (GDM), gut microbiota, inflammation, oxidative stress, and probiotics are increasingly acknowledged. This meta-analysis aimed to summarize the effects of probiotics in GDM, focusing on lifestyle intervention and pre-intervention washout, in addition to metabolic, inflammation, oxidative stress, and pregnancy outcomes. Three electronic databases (i.e., PubMed, Scopus, and CENTRAL) were searched from inception until October 2020. A meta-analysis was performed, and the effect sizes were reported as either mean differences or odds ratios with 95% confidence intervals. Altogether, 10 randomized controlled trials enrolling 594 participants were included. The meta-analysis indicated that probiotics supplementation effectively reduced fasting plasma glucose by 3.10 mg/dL, and subgroup analyses suggested that the duration of intervention, number of species, pre-intervention washout period, and dietary intervention may determine the effects of probiotics. Probiotics also reduced the level of inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and malondialdehyde), incidence of macrosomia, and newborn hospitalization. In conclusion, this meta-analysis suggests that probiotics may have positive effects on metabolic, inflammation, oxidative stress, and neonatal outcomes in women with GDM. Additionally, diet and pre-intervention washout may modify the effects of probiotics. Future studies are warranted on a larger scale to ascertain the clinical significance.