Article - Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials.

Plain Language Summary

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

Reviewer: Gail Brady

15th Feb 2024

Conflict 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

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

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

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Abstract

[{"label":"BACKGROUND","text":"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."},{"label":"METHODS","text":"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."},{"label":"RESULTS","text":"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-\u03b1, and IL-6. Probiotics can also modulate the gut microbiota structure by boosting the enrichment of Bifidobacterium and Lactobacillus."},{"label":"CONCLUSION","text":"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."},{"label":"CLINICAL TRIAL REGISTRATION","text":"https:\/\/www.crd.york.ac.uk\/PROSPERO\/display_record.php?RecordID=281822, identifier CRD42021281822."},{"copyright":"Copyright \u00a9 2023 Zheng, Zhang, Tang, Wu, Zhang, Li, Wang, Wan, Yao and Yuan."}]