Table 2.
Description of the included clinical trials
| References | Study design | Participants’ characteristics | Protocol and groups | Probiotic and dose | Insulin resistance parameter | Effects on glucose metabolism | Other outcomes |
|---|---|---|---|---|---|---|---|
| Rajukmar et al. [44] 2014, Japan | Randomized single-blind | 45 healthy subjects, 20-25 years, BMI 18.5–24.9 kg/m2 | Control, probiotic or synbiotic (FOS) group treated for 6 weeks |
Lactobacillus salivarus UBL S22 4 × 10^9 CFU |
Insulin, HOMA-IR | There were reductions (p < 0.05) in HOMA-IR in probiotic and synbiotic groups, greater in the latter. Insulinemia dropped in all groups (p < 0.05), mainly in the synbiotic group. | BMI decreased only in the synbiotic group (p < 0.05). Probiotic and symbiotic groups had significant increase in HDL-c and reductions in total cholesterol, LDL-c, triglycerides and inflammatory markers (hs-CRP, IL-6, IL-1b and TNF-α) with better results in symbiotic one. |
| Tripolt et al. [24] 2015, Austria | Randomized placebo-controlled | 30 subjects with metabolic syndrome, 52 ± 11 and 55 ± 9 years | Control and probiotic treated for 12 weeks |
Lactobacillus casei shirota 1.95 × 10^10 CFU |
Insulin, HOMA-IR, ISI, Matsuda index, QUICKI | Probiotic-treated group improved ISI (p < 0.01) but insulinemia, HOMA-IR, QUICKI and Matsuda did not differ between groups. | Trimethylamine N-oxide levels reduced in both groups and did not differ between them and were not correlated to HOMA-IR. |
| Firouzi et al. [17] 2016, Malaysia | Randomized double-blind controlled parallel | 136 type 2 diabetic subjects under glybenclamide/metformin, 30–70 years, BMI 18.5–40 kg/m2 | Placebo or probiotics group treated for 12 weeks |
Mix of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus lactis, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium infantis 10^10 CFU each strain |
Insulin, HOMA-IR, QUICKI | Group supplemented with mix of strains improved (p < 0.05) insulin levels and HOMA-IR, while placebo group showed only a trend. QUICKI index did not change. | There was an improvement in HbA1c in the probiotic supplementation group compared to placebo. Participants with normal weight had significant improvement in HbA1c and triglycerides with probiotics supplementation when compared to Ow/Ob participants. |
| Soleimani et al. [22] 2017, Iran | Randomized double-blind placebo-controlled parallel | 60 type 2 diabetic subjects under hemodialysis | Placebo or probiotic groups treated for 12 weeks |
Mix of Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum 2 × 10^9 CFU of each strain |
Insulin, HOMA-IR, QUICKI | Group supplemented with a mix of strains had reductions in insulin levels and HOMA-IR (p < 0.05), and an increase in the QUICKI index, indicating improvement in insulin sensitivity. | Subjects who received probiotic supplements showed benefits on biomarkers of inflammation and oxidative stress (hs-CRP, MDA and total antioxidant capacity). They had significant decreases in HOMA-beta, HbA1c, subjective global assessment scores and total iron binding capacity. |
| Tonucci et al. [45] 2017, Brazil | Randomized double-blind placebo-controlled | 50 type 2 diabetic subjects | Control and probiotic treated for 6 weeks |
Mix of Lactobacillus acidophilus La-5, Bifidobacterium animalis BB-12 10^9 CFU of each strain |
Insulin, HOMA-IR | There was no significant change in insulin levels and HOMA-IR in the groups. | Treated group showed significant decreases in fructosamine, HbA1c, total cholesterol and LDL-c levels. Acetate production increased (p < 0.01) and decreased inflammatory status (TNF-α and resistin levels) in both groups. IL-10 reduced (p < 0.001) only in the control group. |
| Hsieh et al. [46] 2018, Taiwan | Randomized double-blind placebo-controlled | 68 type 2 diabetic subjects, 25–70 years, BMI > 18.5 kg/m2 |
3 groups: placebo, live L. reuteri ADR-1 or heat killed L. reuteri ADR-3 treated for 24 weeks |
Lactobacillus reuteri ADR-1 4 × 10^9 CFU or Lactobacillus reuteri ADR-3 2 × 10^10 CFU |
Insulin, HOMA-IR | Supplemented groups had no significant difference in insulin and HOMA-IR. | Live L. reuteri ADR-1 treated group showed reduction in HbA1c and cholesterol, while heat-killed L. reuteri ADR-3 group decreased blood pressure and the inflammatory cytokine IL-1β. ADR-1 group decreased levels of aspartate aminotransferase, alanine aminotransferase and antioxidant proteins (GPX and SOD). |
| Depommier et al. [23] 2019, Belgium | Randomized double-blind placebo-controlled pilot study | 32 insulin resistant, overweight/obese subjects, 18-70 years, BMI > 25 kg/m2 |
3 groups: placebo, pasteurized A. muciniphila, live A. muciniphila treated for 12 weeks |
Pasteurized A. muciniphila 10^10 CFU A. muciniphila live 10^10 CFU |
Insulin, HOMA-IR | Participants receiving both preparations of A. muciniphila reduced insulin levels in ~30%; this effect was significant between the pasteurized A. muciniphila and placebo groups. Both improved HOMA-IR. | Supplementations were safe. Pasteurized A. muciniphila decreased LPS and dipeptidyl peptidase IV activity. This preparation reduced white blood cells count, total cholesterol, LDL-c, AST but not ALT. Whole-body tissue damage and muscle-specific injury were attenuated as reflected by decreased lactate dehydrogenase and creatine kinase levels. |
FOS: fructooligosaccharides; GPX: glutathione peroxidase; HbA1c: glycated hemoglobin; HDL: high density lipoprotein; HOMA: homeostasis model assessment; Hs-CRP: high-sensitivity C-reactive protein; IL: interleukin; IR: insulin resistance; ISI: insulin sensitivity index; OGTT: oral glucose tolerance test; Ow/Ob (overweight/obese); QUICKI: quantitative insulin sensitivity check index; LDL-c: low density lipoprotein; SOD: superoxide dismutase; TNF-α: tumor necrosis factor