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Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials.
Zheng, Y, Zhang, Z, Tang, P, Wu, Y, Zhang, A, Li, D, Wang, CZ, Wan, JY, Yao, H, Yuan, CS
Frontiers in immunology. 2023;14:1143548
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Intestinal barrier function is closely related to the pathogenesis of various immune and inflammatory diseases. The intestinal microbiota plays an essential role in maintaining gut homeostasis and functionality in the presence of pro-inflammatory and anti-inflammatory microbes. The aim of this study was to comprehensively evaluate the role of probiotics in contributing to intestinal barrier function, and the related immune function, inflammatory status, and gut microbiota composition. This study was a systematic review of 28 articles (qualitative synthesis), and a meta-analysis of 26 randomised controlled trials. Results showed that probiotics could significantly improve intestinal barrier function according to specific indicators. The meta-analysis also indicated that probiotic supplementation could reduce inflammatory factors. Furthermore, it also demonstrated that probiotics could modulate gut microbiota compositions by elevating the abundances of Bifidobacterium and Lactobacillus. Authors conclude that probiotics could improve intestinal barrier function to some extent, but more high-quality randomised controlled studies are needed to reach a solid conclusion.
Expert Review
Conflicts of interest:
None
Take Home Message:
The probiotics Bifidobacterium and Lactobacillus may be beneficial for health by addressing imbalances in gut bacteria (dysbiosis), reducing inflammation in the gut and improving the integrity and function of the gut barrier
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Probiotics are microorganisms that are considered beneficial to health. The aim of this study was to assess the role of probiotics in protecting intestinal barrier function as well as their effects on the composition of gut microbiota, inflammatory status, and immune function for reducing the risk of related diseases.
Methods
26 randomised controlled trials (RCTs) published between 2005-2021 with a total population of n=1891 (n = 955 Intervention, n = 936 controls)) were included in the meta-analysis. Outcome measures were categorised under indicators relating to intestinal barrier function, inflammatory markers, immune function and microbiota composition. Studies were conducted worldwide with participants being healthcare patients or athletes. Study durations ranged from 3 days to 6 months. Different dosages and forms of probiotics were used. Data was pooled for Bifidobacterium, Lactobacillus, Enterobacteriaceae and Enterococcus species.
Results
Gut barrier function in the probiotic groups was improved as measured by transepithelial resistance (TER) mean difference (MD) 5.27 {95% CI, 3.82 to 6.72, p = < 0.00001], lipopolysaccharide (LPS) standardised mean difference (SMD) -0.47 (95% CI, -0.85 to -0.09, p = 0.02), serum zonulin SMD -1.58 (95% CI,-2.49 to -0.66, p = 0.0007), and endotoxin SMD -3.20 (95% CI, -5.41 to - 0.98, p = 0.005).
The inflammatory markers interleukin 6 (IL-6), C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-a) were also improved compared to control groups. Lactobacillus (95% CI p=0.02) and Bifidobacterium (95% CI, p=0.01) enhanced microbial composition, however, Enterobacteriaceae and Enterococcus species did not. Immune function as measured by Immunoglobulin A (IgA), Immunoglobulin G IgG and Immunoglobulin M (IgM) were not improved.
Conclusion
The findings of this study suggest that intestinal barrier function and microbial composition could be improved using probiotics. They were also found to help alleviate inflammation. Further studies of high quality are however needed to confirm these results.
No conflicts of interest were reported.
Clinical practice applications:
The use of the probiotics Bifidobacterium and Lactobacillus may be beneficial for:
- supporting the integrity of gut barrier function
- improving the composition of gut microbiota
- lowering inflammation
Considerations for future research:
High heterogeneity between studies may affect the applicability of the results. Future research development should focus on the following areas:
- testing methods
- study durations
- measuring indicators
- the type and dose of probiotics
Abstract
BACKGROUND Probiotics play a vital role in treating immune and inflammatory diseases by improving intestinal barrier function; however, a comprehensive evaluation is missing. The present study aimed to explore the impact of probiotics on the intestinal barrier and related immune function, inflammation, and microbiota composition. A systematic review and meta-analyses were conducted. METHODS Four major databases (PubMed, Science Citation Index Expanded, CENTRAL, and Embase) were thoroughly searched. Weighted mean differences were calculated for continuous outcomes with corresponding 95% confidence intervals (CIs), heterogeneity among studies was evaluated utilizing I2 statistic (Chi-Square test), and data were pooled using random effects meta-analyses. RESULTS Meta-analysis of data from a total of 26 RCTs (n = 1891) indicated that probiotics significantly improved gut barrier function measured by levels of TER (MD, 5.27, 95% CI, 3.82 to 6.72, P < 0.00001), serum zonulin (SMD, -1.58, 95% CI, -2.49 to -0.66, P = 0.0007), endotoxin (SMD, -3.20, 95% CI, -5.41 to -0.98, P = 0.005), and LPS (SMD, -0.47, 95% CI, -0.85 to -0.09, P = 0.02). Furthermore, probiotic groups demonstrated better efficacy over control groups in reducing inflammatory factors, including CRP, TNF-α, and IL-6. Probiotics can also modulate the gut microbiota structure by boosting the enrichment of Bifidobacterium and Lactobacillus. CONCLUSION The present work revealed that probiotics could improve intestinal barrier function, and alleviate inflammation and microbial dysbiosis. Further high-quality RCTs are warranted to achieve a more definitive conclusion. CLINICAL TRIAL REGISTRATION https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=281822, identifier CRD42021281822.
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The Effects of Sesamin Supplementation on Obesity, Blood Pressure, and Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Sun, Y, Ren, J, Zhu, S, Zhang, Z, Guo, Z, An, J, Yin, B, Ma, Y
Frontiers in endocrinology. 2022;13:842152
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Cardiovascular disease is characterised by modifiable risk factors such as hypertension, elevated cholesterol and obesity. Sesamin, a lignin found in sesame seeds, is suggested to have anti-obesity, antihypertensive, and cholesterol-lowering properties. Therefore, this systematic review and meta-analysis investigated the effectiveness of sesamin as an adjuvant therapy for cardiovascular disease. A total of seven randomised controlled trials are included in this systematic review and meta-analysis. Four studies used 200 mg/day sesamin dosage, and intervention duration ranged from twenty-eight to sixty days. This systematic review and meta-analysis showed improvements in total cholesterol, low-density lipoprotein cholesterol and systolic blood pressure. However, the improvements depended on the duration of sesamin intervention, study design and health status. Further robust studies are required to evaluate the benefits of sesamin in improving cardiovascular disease risk factors due to the high heterogeneity of the included studies in sesamin dosage, participant characteristics and study design. However, healthcare professionals can use the results of this study to understand the potential of sesamin to act as a safe, healthy, and sustainable adjuvant therapy in modifying cardiovascular disease risk factors.
Abstract
AIMS: Sesamin, the main lignin constituent of sesame, plays a pivotal role in regulating physical state. Some studies have evidenced that the supplementation of sesamin may decrease cardiovascular disease risk. The goal of this systematic review was to summarize evidence of the effects of sesamin supplementation on obesity, blood pressure, and lipid profile in humans by performing a meta-analysis of randomized controlled trials. DATA SYNTHESIS Five databases (PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus) were searched electronically from inception to July 2021 to identify randomized controlled trials that assessed the impact of sesamin on obesity, blood pressure, and lipid profile. Weighted mean difference (WMD) and standard deviation (SD) were used to present the major outcomes. CONCLUSIONS Seven trials (n = 212 participants) were included in the overall analysis. Results showed that sesamin supplementation caused a great reduction in TC (WMD: -10.893 mg/dl, 95% CI: -19.745 to -2.041, p = 0.016), LDL-c (WMD: -8.429 mg/dl, 95% CI: -16.086 to -0.771, p = 0.031), and SBP (WMD: -3.662 mmHg, 95% CI: -6.220 to -1.105, p = 0.005), whereas it had no effect on HDL-c, TG, DBP, or weight. Subgroup analysis showed that duration, parallel design, and unhealthy status can affect TC, LDL-c, and SBP evidently. We did not discover a strong link between indicators' changes and duration of supplementation. Sesamin can be used as an obtainable dietary supplement to improve blood pressure and blood lipids, and further as a health product to prevent cardiovascular diseases.
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Association of gestational diabetes mellitus with overall and type specific cardiovascular and cerebrovascular diseases: systematic review and meta-analysis.
Xie, W, Wang, Y, Xiao, S, Qiu, L, Yu, Y, Zhang, Z
BMJ (Clinical research ed.). 2022;378:e070244
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Gestational diabetes mellitus, defined as glucose intolerance with first onset during pregnancy, usually resolves after birth, however, a growing number of long-term observational studies suggest that the impact persists over time. The increased cardiovascular risk in women with gestational diabetes mellitus has been increasingly recognised. The aim of this study was to quantify the risks of overall and type specific cardiovascular and cerebrovascular diseases in women with gestational diabetes mellitus. This study is a systematic review and meta-analysis of fifteen studies. The study included almost nine million women. Results show that participants with a history of gestational diabetes mellitus were at significantly increased risks of cardiovascular and cerebrovascular diseases in general and at variable risks for most common types of cardiovascular and cerebrovascular diseases. Authors conclude that their findings highlight the need for early intervention in women at high risk of gestational diabetes mellitus, and for continuous monitoring of women with a history of gestational diabetes mellitus after pregnancy.
Abstract
OBJECTIVE To quantify the risk of overall and type specific cardiovascular and cerebrovascular diseases as well as venous thromboembolism in women with a history of gestational diabetes mellitus. DESIGN Systematic review and meta-analyses. DATA SOURCES PubMed, Embase, and the Cochrane Library from inception to 1 November 2021 and updated on 26 May 2022. REVIEW METHODS Observational studies reporting the association between gestational diabetes mellitus and incident cardiovascular and cerebrovascular diseases were eligible. Data, pooled by random effects models, are presented as risk ratios (95% confidence intervals). Certainty of evidence was appraised by the Grading of Recommendations, Assessment, Development, and Evaluations. RESULTS 15 studies rated as moderate or serious risk of bias were included. Of 513 324 women with gestational diabetes mellitus, 9507 had cardiovascular and cerebrovascular disease. Of more than eight million control women without gestational diabetes, 78 895 had cardiovascular and cerebrovascular disease. Compared with women without gestational diabetes mellitus, women with a history of gestational diabetes mellitus showed a 45% increased risk of overall cardiovascular and cerebrovascular diseases (risk ratio 1.45, 95% confidence interval 1.36 to 1.53), 72% for cardiovascular diseases (1.72, 1.40 to 2.11), and 40% for cerebrovascular diseases (1.40, 1.29 to 1.51). Women with gestational diabetes mellitus showed increased risks of incident coronary artery diseases (1.40, 1.18 to 1.65), myocardial infarction (1.74, 1.37 to 2.20), heart failure (1.62, 1.29 to 2.05), angina pectoris (2.27, 1.79 to 2.87), cardiovascular procedures (1.87, 1.34 to 2.62), stroke (1.45, 1.29 to 1.63), and ischaemic stroke (1.49, 1.29 to 1.71). The risk of venous thromboembolism was observed to increase by 28% in women with previous gestational diabetes mellitus (1.28, 1.13 to 1.46). Subgroup analyses of cardiovascular and cerebrovascular disease outcomes stratified by study characteristics and adjustments showed significant differences by region (P=0.078), study design (P=0.02), source of data (P=0.005), and study quality (P=0.04), adjustment for smoking (P=0.03), body mass index (P=0.01), and socioeconomic status (P=0.006), and comorbidities (P=0.05). The risk of cardiovascular and cerebrovascular diseases was, however, attenuated but remained significant when restricted to women who did not develop subsequent overt diabetes (all gestational diabetes mellitus: 1.45, 1.33 to 1.59, gestational diabetes mellitus without subsequent diabetes: 1.09, 1.06 to 1.13). Certainty of evidence was judged as low or very low quality. CONCLUSIONS Gestational diabetes mellitus is associated with increased risks of overall and type specific cardiovascular and cerebrovascular diseases that cannot be solely attributed to conventional cardiovascular risk factors or subsequent diabetes.
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Consumption of ultra-processed foods and health outcomes: a systematic review of epidemiological studies.
Chen, X, Zhang, Z, Yang, H, Qiu, P, Wang, H, Wang, F, Zhao, Q, Fang, J, Nie, J
Nutrition journal. 2020;19(1):86
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Unhealthy diets are recognized as a major determinant of the occurrence of non-communicable diseases (NCDs). The aim of this study was to summarize the evidence for the association between ultra-processed food (UPFs) consumption and health outcomes. This study is a systemic review of 20 published epidemiological studies (12 cohort and 8 cross-sectional studies), with a total of 334,114 participants and 10 diseases. Results indicate a positive association between UPFs consumption and risk of all-cause mortality, overall cardiovascular diseases, coronary heart diseases, cerebrovascular diseases, hypertension, metabolic syndrome, overweight and obesity, depression, irritable bowel syndrome, overall cancer, postmenopausal breast cancer, gestational obesity, adolescent asthma and wheezing, and frailty. However, on the contrary, there was not an obvious association with cardiovascular disease mortality, prostate and colorectal cancer, gestational diabetes mellitus and gestational overweight. Authors conclude that their findings encouraged a decrease in UPFs consumption and an increase in the proportion of unprocessed or minimally processed foods, such as fruits and vegetables.
Abstract
BACKGROUND Consumption of ultra-processed foods (UPFs) plays a potential role in the development of obesity and other diet-related noncommunicable diseases (NCDs), but no studies have systematically focused on this. This study aimed to summarize the evidence for the association between UPFs consumption and health outcomes. METHODS A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies. Epidemiological studies were included, and identified studies were evaluated for risk of bias.A narrative review of the synthesized findings was provided to assess the association between UPFs consumption and health outcomes. RESULTS 20 studies (12 cohort and 8 cross-sectional studies) were included in the analysis, with a total of 334,114 participants and 10 health outcomes. In a narrative review, high UPFs consumption was obviously associated with an increased risk of all-cause mortality, overall cardiovascular diseases, coronary heart diseases, cerebrovascular diseases, hypertension, metabolic syndrome, overweight and obesity, depression, irritable bowel syndrome, overall cancer, postmenopausal breast cancer, gestational obesity, adolescent asthma and wheezing, and frailty. It showed no significant association with cardiovascular disease mortality, prostate and colorectal cancers, gestational diabetes mellitus and gestational overweight. CONCLUSIONS This study indicated a positive association between UPFs consumption and risk of several health outcomes. Large-scale prospective designed studies are needed to confirm our findings.
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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.