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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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X
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.
2.
Are probiotics, prebiotics, and synbiotics beneficial in primary thyroid diseases? A systematic review with meta-analysis.
Zawadzka, K, Kałuzińska, K, Świerz, MJ, Sawiec, Z, Antonowicz, E, Leończyk-Spórna, M, Abadi, AK, Trofimiuk-Müldner, M, Bała, MM
Annals of agricultural and environmental medicine : AAEM. 2023;30(2):217-223
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Irregularities in intestinal microbial composition are thought to be correlated with thyroid dysfunction. Supplementation of prebiotics, probiotics and synbiotics are gaining momentum in recent times in improving health in general. This systematic review of randomised controlled trials was conducted to summarise the up-to-date evidence on the therapeutic potential of prebiotics, probiotics and synbiotics in the treatment of thyroid disease. The meta-analysis did not show beneficial effects on thyroid hormone balance, BMI or levothyroxine dosage reduction. Supplementation with Lactobacillus and Bifidobacterium resulted in improvement in constipation and a statistically non-significant reduction in thyroid-stimulating hormone in adult participants with hypothyroidism. Further robust long-term studies are required to evaluate the efficacy of prebiotics, probiotics and synbiotics in thyroid disease treatment as the availability of the number of studies included in this systematic review was limited. However, healthcare professionals can use the review to understand the current evidence in this area and the correlation between gut microbial alterations and thyroid disease.
Abstract
INTRODUCTION AND OBJECTIVE A number of studies indicate the presence of a thyroid-gut axis and the important influence of the gut microbiota on thyroid function. As prebiotics, probiotics and synbiotics show therapeutic potential in the treatment of intestinal dysbiosis, the aim of this review is to evaluate the efficacy of their supplementation in primary thyroid diseases. REVIEW METHODS Electronic databases (Ovid MEDLINE, Embase, CENTRAL), registers of clinical trials, and grey literature up to 6 October 2022 were searched for randomised controlled trials (RCTs) meeting pre-specified inclusion criteria. The protocol was registered in PROSPERO (CRD42021235054). BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE After screening 1,721 references, two RCTs were identified, which included 136 hypothyroid participants in total. Meta-analysis of the results after eight weeks of supplementation with predominantly Lactobacillus and Bifidobacterium strains indicated a clinically and statistically nonsignificant decrease in TSH (MD -0.19 mIU/L; 95% CI -0.43 to 0.06; I2= 0%), and no effect on fT3 levels (MD 0.01 pg/mL; 95% CI-0.16 to 0.18; I2= 0%). Data from single studies indicated no significant change in the levels of fT4, thyroid auto-antibodies, BMI, levothyroxine doses, and severity of symptoms measured with validated scales. Only constipation scores showed significant improvement (MD -8.71 points in the Faecal Incontinence Questionnaire; 95% CI -15.85 to -1.57; I2= 0%). SUMMARY Low-certainty evidence from two randomised trials, suggests that routine administration of probiotics, prebiotics or synbiotics may result in little to no benefit in patients with primary hypothyroidism.
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Gluten and FODMAPs Relationship with Mental Disorders: Systematic Review.
Aranburu, E, Matias, S, Simón, E, Larretxi, I, Martínez, O, Bustamante, MÁ, Fernández-Gil, MDP, Miranda, J
Nutrients. 2021;13(6)
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There is growing evidence that gluten and FODMAPs, such as fermentable oligosaccharides, disaccharides, monosaccharides and polyols, can cause gastrointestinal symptoms, inflammation, and immune responses in patients with celiac disease and irritable bowel syndrome. In addition, a high intake of gluten and FODMAPs may also be associated with neurological and psychiatric disorders. Thirteen studies were included in this systematic review to examine the relationship between gluten and FODMAP consumption and illnesses affecting the central nervous system. In addition, the studies examined the effects of potential dietary strategies that consider gluten and FODMAP intake on mental disorders, anxiety, depression, schizophrenia, Alzheimer’s disease, and autism spectrum disorders. Several possible mechanisms identified in this systematic review could contribute to neurological and psychiatric disorders, including the release of proinflammatory cytokines, immune responses, gut dysbiosis, intestinal permeability, and interactions between the gut-brain axis. In patients with fibromyalgia, celiac disease, and irritable bowel syndrome, avoiding or limiting gluten may reduce depression, anxiety, and cognitive impairment. However, the effects of a low-FODMAP diet on the central nervous system are inconclusive. There is some evidence that gluten-free diets can improve cognition in schizophrenia patients. In addition, those with autism spectrum disorders may benefit from a gluten-free diet and a low-FODMAP diet. Further robust research is required to evaluate the beneficial effects of interventions that avoid or restrict the consumption of foods high in FODMAPs and gluten. However, healthcare professionals can use the results of this systematic review to understand the potential benefits of therapeutic interventions that consider the intake of FODMAPs and gluten on illnesses affecting the central nervous system and their possible mechanisms of action.
Abstract
Nowadays, gluten and FODMAP food components (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) are increasingly studied due to their possible relation with extraintestinal-associated conditions. In recent years, gluten-free diets (GFD) and low-FODMAP diets (LFD) are becoming more popular not only in order to avoid the food components that cause intolerances or allergies in some people, but also due to the direct influence of marketing movements or diet trends on feeding habits. Likewise, neurological and psychiatric diseases are currently of increasing importance in developed countries. For this reason, a bibliographic systematic review has been carried out to analyse whether there is a pathophysiological relationship between the dietary intake of gluten or FODMAPs with mental disorders. This review collects 13 clinical and randomized controlled trials, based on the PRISMA statement, which have been published in the last ten years. Based on these results, limiting or ruling out gluten or FODMAPs in the diet might be beneficial for symptoms such as depression, anxiety (7 out of 7 articles found any positive effect), or cognition deficiency (improvements in several cognition test measurements in one trial), and to a lesser extent for schizophrenia and the autism spectrum. Nevertheless, further studies are needed to obtain completely reliable conclusions.
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Postoperative changes of the microbiome: are surgical complications related to the gut flora? A systematic review.
Lederer, AK, Pisarski, P, Kousoulas, L, Fichtner-Feigl, S, Hess, C, Huber, R
BMC surgery. 2017;17(1):125
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Infections following gastrointestinal surgery are common and patients routinely receive antibiotic medications to reduce the risks involved. Recent reviews have suggested that some of these complications might be related to the patient’s gut bacteria profile. This systematic review of 10 studies, including 677 patients, aimed to identify the relationship between post-operative infections and the gut microbiome. All studies reported a post-operative change to the gut flora, with 5 studies showing a reduction in bacteria present. Surgery tended to lead to an increase in disease causing bacteria and a reduction in health giving bacteria. The rate of post-operative complications was lower in the groups treated with pre- and pro-biotics, suggesting that there might be a relationship between gut flora and infections following surgery. There remains uncertainty however, due to the shortcomings of the methodologies employed by the studies.
Abstract
BACKGROUND The purpose of this review was to identify the relationship between the gut microbiome and the development of postoperative complications like anastomotic leakage or a wound infection. Recent reviews focusing on underlying molecular biology suggested that postoperative complications might be influenced by the patients' gut flora. Therefore, a review focusing on the available clinical data is needed. METHODS In January 2017 a systematic search was carried out in Medline and WebOfScience to identify all clinical studies, which investigated postoperative complications after gastrointestinal surgery in relation to the microbiome of the gut. RESULTS Of 337 results 10 studies were included into this analysis after checking for eligibility. In total, the studies comprised 677 patients. All studies reported a postoperative change of the gut flora. In five studies the amount of bacteria decreased to different degrees after surgery, but only one study found a significant reduction. Surgical procedures tended to result in an increase of potentially pathogenic bacteria and a decrease of Lactobacilli and Bifidobacteria. The rate of infectious complications was lower in patients treated with probiotics/symbiotics compared to control groups without a clear relation to the systemic inflammatory response. The treatment with synbiotics/probiotics in addition resulted in faster recovery of bowel movement and a lower rate of postoperative diarrhea and abdominal cramping. CONCLUSIONS There might be a relationship between the gut flora and the development of postoperative complications. Due to methodological shortcomings of the included studies and uncontrolled bias/confounding factors there remains a high level of uncertainty.