Glucose Parameters, Inflammation Markers, and Gut Microbiota Changes of Gut Microbiome-Targeted Therapies in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

2025-06-09
The Journal of clinical endocrinology and metabolism 110(10)
- Xin Zhou
- Wenbin Zheng
- Wen Kong
- Jiaoyue Zhang
- Yunfei Liao
- Jie Min
- Tianshu Zeng

PubMed: 40489582
DOI: 10.1210/clinem/dgaf340

Study Design

Type: Meta-Analysis
Sample size: n = 3,390
Population: subjects with T2DM
Methods: Meta-analysis of 54 randomized controlled trials; four databases were searched for RCTs that included subjects with T2DM who received MTTs

Purpose

This meta-analysis aims to summarize the effects of gut microbiome-targeted therapies (MTTs) on glucometabolic, inflammatory factors and gut microbiota in patients with type 2 diabetes mellitus (T2DM).

Methods

Four databases were searched for randomized controlled trials (RCTs) that included subjects with T2DM who received MTTs. All results were presented as standardized mean difference (SMD) or mean difference (MD) and 95% CIs. In addition, subgroup analyses were performed according to region, type of MTTs, number of probiotic strains, probiotics dose, prebiotics dose, duration of MTTs, mean age, and baseline body mass index.

Results

A total of 54 RCTs were included, encompassing 60 groups and 3390 subjects. Overall, MTTs intervention decreased fasting plasma glucose (MD = -7.97 mg/dL [95% CI = -10.82, -5.12]; P < .00001), 2-hour postprandial blood glucose (MD =  -43.30 mg/dL [95% CI = -75.83, -10.77]; P = .009), fasting insulin (MD = -1.73 uU/mL [95% CI = -2.63, -0.84]; P = .0001), HbA1c (MD = -0.28%, [95% CI = -0.39, -0.17]; P < .00001), and homeostatic model assessment of insulin resistance (MD =-0.53 [95% CI = -0.85, -0.20]; P = .0002). Furthermore, MTTs supplementation reduced high-sensitivity C-reactive protein, tumor necrosis factor alpha, and lipopolysaccharides. Meanwhile, the levels of interleukin-10 were increased. Moreover, the abundance of Actinobacteria, Lactobacillus, and Lactobacillus casei subgroup increased.

Conclusion

MTTs modestly improved glucometabolic parameters, reduced pro-inflammatory cytokines, and enriched beneficial microbes (eg, Actinobacteria, Lactobacillus) in subjects with T2DM. However, heterogeneity and limited long-term data highlight the need for large-scale RCTs.

Research Insights

Bifidobacterium bifidum BB-06→Improved Glycemia
MTTs intervention decreased fasting plasma glucose... 2-hour postprandial blood glucose... fasting insulin... HbA1c... and homeostatic model assessment of insulin resistance
Effect
Beneficial
Effect size
Small
Bifidobacterium bifidum BB-06→Improved Gut Microbiota
the abundance of Actinobacteria, Lactobacillus, and Lactobacillus casei subgroup increased.
Effect
Beneficial
Effect size
Small
Bifidobacterium bifidum BB-06→Reduced Inflammation
MTTs supplementation reduced high-sensitivity C-reactive protein, tumor necrosis factor alpha, and lipopolysaccharides. Meanwhile, the levels of interleukin-10 were increased.
Effect
Beneficial
Effect size
Small
Bifidobacterium bifidum Bb-02→Improved Glycemia
MTTs intervention decreased fasting plasma glucose... 2-hour postprandial blood glucose... fasting insulin... HbA1c... and homeostatic model assessment of insulin resistance
Effect
Beneficial
Effect size
Small
Bifidobacterium bifidum Bb-02→Improved Gut Microbiota
the abundance of Actinobacteria, Lactobacillus, and Lactobacillus casei subgroup increased.
Effect
Beneficial
Effect size
Small
Bifidobacterium bifidum Bb-02→Reduced Inflammation
MTTs supplementation reduced high-sensitivity C-reactive protein, tumor necrosis factor alpha, and lipopolysaccharides. Meanwhile, the levels of interleukin-10 were increased.
Effect
Beneficial
Effect size
Small
Bifidobacterium breve Bb-18→Improved Glycemia
MTTs intervention decreased fasting plasma glucose... 2-hour postprandial blood glucose... fasting insulin... HbA1c... and homeostatic model assessment of insulin resistance
Effect
Beneficial
Effect size
Small
Bifidobacterium breve Bb-18→Increased Beneficial Gut Microbiota
the abundance of Actinobacteria, Lactobacillus, and Lactobacillus casei subgroup increased.
Effect
Beneficial
Effect size
Small
Bifidobacterium breve Bb-18→Reduced Inflammation
MTTs supplementation reduced high-sensitivity C-reactive protein, tumor necrosis factor alpha, and lipopolysaccharides. Meanwhile, the levels of interleukin-10 were increased.
Effect
Beneficial
Effect size
Small
Bifidobacterium lactis Bb-02→Improved Glycemia
MTTs intervention decreased fasting plasma glucose... 2-hour postprandial blood glucose... fasting insulin... HbA1c... and homeostatic model assessment of insulin resistance
Effect
Beneficial
Effect size
Small
Bifidobacterium lactis Bb-02→Improved Glycemic Control
MTTs intervention decreased fasting plasma glucose (MD = -7.97 mg/dL [95% CI = -10.82, -5.12]; P < .00001), 2-hour postprandial blood glucose (MD = -43.30 mg/dL [95% CI = -75.83, -10.77]; P = .009), fasting insulin (MD = -1.73 uU/mL [95% CI = -2.63, -0.84]; P = .0001), HbA1c (MD = -0.28%, [95% CI = -0.39, -0.17]; P < .00001), and homeostatic model assessment of insulin resistance (MD = -0.53 [95% CI = -0.85, -0.20]; P = .0002).
Effect
Beneficial
Effect size
Moderate
Bifidobacterium lactis Bb-02→Increased Beneficial Gut Microbiota
the abundance of Actinobacteria, Lactobacillus, and Lactobacillus casei subgroup increased.
Effect
Beneficial
Effect size
Small
Bifidobacterium lactis Bb-02→Reduced Inflammation
MTTs supplementation reduced high-sensitivity C-reactive protein, tumor necrosis factor alpha, and lipopolysaccharides. Meanwhile, the levels of interleukin-10 were increased.
Effect
Beneficial
Effect size
Small
Lactobacillus acidophilus L-92→Improved Glycemia
MTTs intervention decreased fasting plasma glucose... 2-hour postprandial blood glucose... fasting insulin... HbA1c... and homeostatic model assessment of insulin resistance
Effect
Beneficial
Effect size
Small
Lactobacillus acidophilus L-92→Improved Gut Microbiota
the abundance of Actinobacteria, Lactobacillus, and Lactobacillus casei subgroup increased.
Effect
Beneficial
Effect size
Small
Lactobacillus acidophilus L-92→Reduced Inflammation
MTTs supplementation reduced high-sensitivity C-reactive protein, tumor necrosis factor alpha, and lipopolysaccharides. Meanwhile, the levels of interleukin-10 were increased.
Effect
Beneficial
Effect size
Small
Lactobacillus acidophilus LA-02→Improved Glycemia
MTTs intervention decreased fasting plasma glucose... 2-hour postprandial blood glucose... fasting insulin... HbA1c... and homeostatic model assessment of insulin resistance
Effect
Beneficial
Effect size
Small
Lactobacillus acidophilus LA-02→Improved Gut Microbiota
the abundance of Actinobacteria, Lactobacillus, and Lactobacillus casei subgroup increased.
Effect
Beneficial
Effect size
Small
Lactobacillus acidophilus LA-02→Reduced Inflammation
MTTs supplementation reduced high-sensitivity C-reactive protein, tumor necrosis factor alpha, and lipopolysaccharides. Meanwhile, the levels of interleukin-10 were increased.
Effect
Beneficial
Effect size
Small