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Table 2 Description of the included clinical trials

From: Probiotics supplementation and insulin resistance: a systematic review

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.

  1. 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