Introduction
Methods
Search strategy
Eligibility criteria
Data handling
Analysis and interpretation
Results
Animal studies
Reference | Research protocol (duration and experimental groups) | Probiotic type and dose | Insulin resistance parameters | Effects on glucose metabolism | Other significant outcomes |
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Andersson et al. [18] 2009, Sweden | 18 weeks Groups: Control (HFD diabetic control) Treated Lp DSM 15313 (HFD + probiotic) | Lactobacillus plantarum DSM 15313 2.4 × 10^9 CFU | Plasma insulin in OGTT and IVGTT | At the end of the intervention, insulin levels in response to OGTT (p < 0.05)—but not to IVGTT—were lower in the treated group than the control group. | Body weight increase in the probiotic group seemed to be due to lean mass gain rather than fat mass. IL-6 was below detection limit and signs of systemic inflammation were not detected. No difference in total cholesterol, non-esterified free fatty acids and adiponectin levels were found. |
Kondo et al. [19] 2010, Japan | 8 weeks Groups: Control (HFD diabetic control) B-3L (HFD + B. breve B-3L) B-3H (HFD + B. breve B-3H) | Bifidobacterium breve B-3L 10^8 CFU or Bifidobacterium breve B-3H 10^9 CFU | Plasma insulin and HOMA-IR | Reductions in glucose, insulin and HOMA-IR, plasma glucose were found only in treated groups (p < 0.05) being more pronounced in B. breve B-3H than B-3L. | Supplemented groups had lower mean body and epididymal fat weight. Expressions of adiponectin and proglucagon genes were higher in both probiotic groups; fasting-induced adipose factor expression was higher only in the B-3H group. No change was observed in Bacteroidetes-to-Firmicutes ratio. |
Amar et al. [20] 2011, France | 6 weeks 8 Experiments: Exp.1, 4, 5: control; HFD-fed for 1 wk; HFD-induced diabetic 4 weeks Exp.2: WT control, HFD-fed for 4 weeks, Nod1 −/− NC, Nod1 −/− 4 weeks WT control, HFD-fed for 4 weeks, Nod2 −/− NC, Nod2 −/− 4 weeks WT, ob/ob, ob/ob CD14−/−, CD14 −/− Exp.3: WT control, Myd88 −/− Exp.6, 7: L. lactis, L. lactis leptin Exp.8: NC, HFD + vehicle, HFD + B420 | Bifidobacterium animalis subsp. lactis 420 10^9 CFU | Fasting insulin and AUC after OGTT and IPGTT | In OGTT, Nod2 knockout mice had similar glycemia to HFD-fed WT. Glycemic values of WT HFD-fed were significantly higher than other knockout groups for Nod1 and WT controls. In IPGTT, ob/ob mice had the highest glycemic level compared to ob/ob cd14−/−, WT and cd14 −/− groups (p < 0.05), and these 3 had similar values. In IPGTT, comparing knockouts for myeloid differentiation protein (Myd88) and WT, fasting glucose, insulin and insulin resistance in the Myd88 knockout were increased compared to WT. Glucose intolerance was slightly improved and fasting insulin remained unchanged when comparing to L. lactis and L. lactis leptin groups. Fasting glucose and insulin fell after L. lactis intervention (p < 0.05). | Lack of microbial pattern recognition receptors nucleotide-binding oligomerization domain-containing protein 1 (Nod1) or cluster of differentiation 14 (CD14) prevented intestinal bacteria translocation and inflammation, while Myd88 knockout and ob/ob mouse showed increased translocation. Probiotic treatment can reduce dysbiosis and regulate intestinal bacterial adherence, translocation and metabolism, resulting in improvement of inflammation and metabolic status. |
Zhang et al. [25] 2013, China | 9 weeks or 13 weeks Groups: Control LP (L. casei-Zhang preventive) HMI (hyperinsulinemia model-9 weeks) LT (L. casei Zhang -therapeutic) HMII (hyperinsulinemia model-13 weeks) | Lactobacillus casei Zhang 10^9 CFU | Insulin AUC after OGTT | Fructose-treated group developed impaired glucose tolerance. Compared to HMI group, the LP had a non-significant decrease in the glucose peak, while LT reduced the glycemic peak compared to the HMII group (p = 0.048). During OGTT, the LP group prevented worsening of glucose intolerance, with improvement in glucose tolerance at HMI and in the LT group (p < 0.05). | Probiotic-treated group increased osteocalcin level and improved several markers of liver function and gene expressions (bile acids secretion, decreased malonaldehyde levels and upregulation of liver X receptor alpha, peroxisome proliferator-activated receptor and adiponectin receptor 2 gene expression). |
Toral et al. [28] 2014, Spain | 12 weeks-Exp.1: Control (ND control) Control-treated (ND + probiotic) Obese (HFD diabetic control) Obese-treated (HFD + probiotic) 2 weeks-Exp.2: Control (ND control) Control-treated (ND + probiotic) | Lactobacillus coryniformis CECT5711 10^8 CFU | Fasting insulin, HOMA-IR and AUC after OGTT | AUC after an OGTT (p < 0.01) and HOMA-IR (p < 0.05) were worse in mice under HFD than in controls. Non-treated obese group had higher AUC (p < 0.01) than the probiotic-treated obese group, whose performance was similar to control groups. Probiotic treatment reduced basal glycemia and insulin resistance, and improved glucose tolerance without significant changes in insulinemia. | Treatment induced changes in microbiota composition causing an improvement in gut barrier and metabolic endotoxemia (reduced LPS levels). Also, the decreased TNF-α expression in liver indicated an improved inflammatory status. An endothelial-protective effect was suggested by reversing the endothelial dysfunction related nitric oxide-dependent vasodilatation and restoring the increased vessel superoxide levels by reducing the NADPH oxidase activity and increasing antioxidant enzymes. |
Alard et al. [42] 2016, France | 7 weeks Groups: LFD (ND control) LFD + PBS (ND + multistrain) HFD (HFD diabetic control) HFD + PBS (HFD + multistrain) | Multi-strain mixture: Lactobacillus rhamnosus LMG S-28148 Bifidobacterium lactis LMG P-28149 5 × 10^8 CFU of each strain | Fasting insulin, HOMA-IR and AUC after IPGTT | AUC after IPGTT indicated that HFD-fed animals treated with a multi-strain probiotic mixture reduced fasting glucose and insulin levels (p < 0.05) in contrast to those not treated with probiotics. HOMA-IR was lower in the HFD-mix group compared to the control group (p < 0.05), suggesting greater insulin sensitivity that was confirmed by the IPGTT. | Probiotic mixture remodelled immune cells in adipose tissue and improved adiposity and dyslipidemia. Microbiota composition (increased A. muciniphila and Rikenellaceae and decreased Lactobacillaceae abundances) was changed, expression of the SFCA receptor was restored, ameliorating intestinal uptake of fatty acids. In in vitro simulation of luminal and mucosal environment, the probiotic mixture favored butyrate and propionate production. |
Hsieh et al. [29] 2016, Taiwan | 12 weeks Groups: Control (ND control) Control + HK Lr263 (ND + L. reuteri Lr263 HK) Control + Lr263 (ND + L. reuteri Lr263 live) HFD (HFD diabetic control) HFD + HK Lr263 (HFD + L. reuteri Lr263 HK) HFD + live Lr263 (HFD + L. reuteri Lr263 live) | Lactobacillus reuteri GMNL-263 (HK Lr263) Heat-killed/Lyophilized 2 × 10^9 CFU Lactobacillus reuteri GMNL-263 (Lr263) Live 2 × 10^9 CFU | Fasting insulin, HOMA-IR and AUC after OGTT | HOMA-IR was higher in HFD group than in control one but reduced after treatments with lyophilized or live probiotics (p < 0.05). It did not differ between the control groups. Glycemic values in OGTT revealed that administration of live or lyophilized Lr263 attenuated HFD-induced glycemia increase. No differences in OGTTs of the 3 control groups, with or without probiotics, were observed. Increased insulin and glucose levels in HFD group were reduced by administration of live or lyophilized Lr263 (p < 0.05). | Live or lyofilized probiotics reduced weight gain and improved lipid profile. They suppressed the increased macrophage infiltration in adipose tissue and decreased proinflammatory-associated gene expressions in adipose and hepatic tissues contributing to attenuate hepatic steatosis. Treatment restored the proportion of probiotic bacteria and decreased pathogens improving intestinal barrier. |
Lim et al. [31] 2016, Korea | 4,5 weeks Groups: LFD (ND control) LFD-67 (ND + L. sakei OK67) HFD (HFD diabetic control) HFD-67 (HFD + L. sakei OK67) | Lactobacillus sakei OK67 10^9 CFU | Fasting insulin and AUC after OGTT | Probiotic treatment reduced plasma glucose and AUC after OGTT in animals under HFD (p < 0.05) but not in mice with LFD. Animals fed with HFD increased insulin levels and probiotic treatment reduced the increase in insulinemia (p < 0.05). | Probiotic reduced inflammation by decreasing TNF-α and IL-1β expressions and increasing IL-10 and tight junction protein expressions in the colon. Treatment inhibited NF-κB activation in LPS-stimulated peritoneal macrophages. Downregulated expression of peroxisome proliferator-activated receptor γ, fatty acid synthase, and TNF-α in adipose tissue were also observed. |
Shang et al. [15] 2016, China | 12 weeks Groups: ND (ND control) HFD (HFD diabetic control) HFD-Cb (HFD + probiotic) | Clostridium butyricum CGMCC0313.1 2 × 10^8 CFU | Fasting insulin and glucose tolerance during ITT and OGTT | The performance of OGTT and ITT for treated group revealed an improved glucose tolerance and relatively better insulin sensitivity with a reduced fasting insulinemia. | Treated group had lower weight gain, hepatic steatosis, accumulation of lipids in the liver. Also, lower TNF-α, IL-1B and MCP-1 levels, and higher IL-10 and IL-22 levels were found. SCFA production was restored, claudin-1 and occludin expressions were increased and LPS level decreased. |
Balakumar et al. [33] 2016, India | 24 weeks Groups: NPD (ND control) HFD (diabetic control) HFD + LGG (HFD + L. rhamnosus GG) HFD-MTCC 5690 (HFD + L. rhamnosus MTCC5690) HFD-MTCC 5689 (HFD + L. rhamnosus MTCC5689) HFD + metformin HFD + vildagliptin | Lactobacillus rhamnosus GG 1.5 × 10^9 CFU Lactobacillus plantarum Lp91 (MTCC5690) 1.5 × 10^9 CFU Lactobacillus fermentum Lf1 (MTCC5689) 1.5 × 10^9 CFU | Fasting insulin, HOMA-IR, AUC after OGTT and glucose tolerance during ITT | After 16 weeks, there was a significant improvement in insulin sensitivity (reduction in HOMA-IR, p < 0.05) in all treated groups but not in HFD control. Groups treated with LGG, MTCC5689, metformin or vildagliptin had reductions in glucose levels during OGTT (p < 0.05). All groups treated with drugs or probiotics improved the AUC after ITT but not HFD control group. | Probiotic interventions (especially MTCC5689) reduced lipids, normalized GLP-1 levels and restored endoplasmatic reticulum stress markers. Increased transcription for tight junction markers and decreased LPS levels were also observed. Except for LGG, the other 2 probiotic groups increased transcription for adiponectin in fat tissue. Transcriptions of inflammatory (TNF-α, IL-6 and MCP-1), lipogenesis, and gluconeogenesis gene expression in liver were reduced and normalized by probiotic intervention. |
Zhao et al. [26] 2017, China | 5 weeks Groups: NCD (ND control) NCD + P (ND probiotic) | Akkermansia muciniphila 2 × 10^8 CFU | Fasting insulin and AUC after IPGTT | Despite no change in fasting plasma glucose, supplementation with A. muciniphila to mice fed with a standard diet, IPGTT showed improvement in glucose tolerance (p < 0.01). Fasting insulinemia was comparable between the two groups. | Intervention induced reduction in body weight gain, fat mass and gene expressions related to fatty acid synthesis and transport in liver and muscle—alleviating endoplasmic reticulum stress; and in low-grade inflammation reflected by increased anti-inflammatory factors such as α-tocopherol and β-sitosterol and decreased levels of LPS-binding protein and leptin.. |
Aoki et al. [41] 2017, Japan | 6 weeks Exp.1: NCD (ND control) HFD (HFD diabetic control) HFD BlaG (B. lactis GCL2505) Exp.2: HFD (HFD diabetic control) HFD BlaG (B. lactis GCL2505) HFD BloJ (B. longum JCM1217T) | Bifidobacterium lactis GCL2505 (BlaG) 10^9 CFU Bifidobacterium longum JCM1217T (BloJ) 10^9 CFU | Insulin and AUC after OGTT | Improvement in glucose tolerance assessed by OGTT in BlaG group (p < 0.05) when compared to diabetic control and BloJ groups. No significant difference was detected between the last 2 groups. | BlaG treatment improved metabolic disorders by modulating gut microbiota enhancing Bifidobacterium, reduced visceral fat accumulation and increased GLP-1 and SCFA levels (especially acetate). BloJ had no effect on these parameters. |
Singh et al. [34] 2017, India | 6 weeks Groups: Control (ND control) HFD + SM (HFD diabetic control) HFD + LGG (HFD + L. rhamnosus GG) HFD + 17 (HFD + L. rhamnosus NCDC17) | Lactobacillus rhamnosus GG 8 to 8.5 log CFU Lactobacillus rhamnosus NCDC17 9.5 to 10 log CFU | Fasting insulin and AUC after OGTT | Treated groups had significant reductions in fasting insulin and AUC (p < 0.05) compared to diabetic control group. | LC group had lower plasma glucose, glycated hemoglobin, leptin, TNF-α, IL-6, LDL-c and higher HDL-c levels. Probiotic treatment increased expressions of phosphatidylinositol-3-kinase and glycogen synthase genes and decreased of glycogen synthase kinase 3 beta mRNA. Pancreas histology showed a recovery of islets cells. Improved production of SCFA (mainly acetate and butyrate) and decreased Firmicutes-to-Bacteroidetes ratio were found. |
Li et al. [32] 2017, China | 8 weeks Groups: NC (ND control) DC (HFD diabetic control) P (HFD + pioglitazone) LC (HFD + L. casei) | Lactobacillus casei CCFM419 8 × 10^9 CFU | Fasting insulin, HOMA-IR, AUC after OGTT and glucose tolerance during ITT | Probiotic treated but not control animals showed decreases in HOMA-IR (p < 0.05), indicating improvement in insulin sensitivity in diabetic mice. LC group showed significant lower glucose AUC after OGTT, suggesting that the probiotic could delay the onset of hyperglycemia and ameliorate the impaired glucose tolerance. Probiotic and pioglitazone brought similar results. | LC group had lower fasting and postprandial glucose, glycated hemoglobin, leptin, TNF-α, IL-6 and LDL-c levels and higher HDL-c. Probiotic treatment increased expressions of phosphatidylinositol-3-kinase and glycogen synthase genes and decreased of glycogen synthase kinase 3 beta mRNA. Pancreas histology showed a recovery of islets cells. Also, decreased Firmicutes-to-Bacteroidetes and improved production of SCFA (acetate and butyrate) were found. |
Wang et al. [16] 2017, China | 12 weeks Groups: C (ND control) M (HFD diabetic control) P (HFD + pioglitazone) 10^8 (HFD + L. casei 10^8) 10^9 (HFD + L. casei 10^9) 10^10 (HFD + L. casei 10^10) | Lactobacillus casei CCFM419 10^8 or 10^9 or 10^10 CFU | Fasting insulin, HOMA-IR and glucose AUC during OGTT | Teatment induced lower glucose AUC, insulin level and HOMA-IR (p < 0.05). Probiotic doses of 10^8 and 10^9 CFU showed better ability of improving insulin resistance than 10^10 CFU. | Probiotic groups had lower TNF-α levels and protective effects in islet cells. Acetate, butyrate and GLP-1 levels were increased (at 10^9 and 10^10 CFU doses) and Firmicutes-to-Bacteroidetes ratio reduced. All doses of probiotic had some improvement in lipid profile, but only the 10^9 CFU dose had significant reduction in triglycerides, total cholesterol and LDL-c. The same dose recovered significantly stress oxidative markers (SOD, glutationa, GPx and MDA) and decreased IL-6. |
Bagarolli et al. [43] 2017, Brazil | 5 weeks Groups: C (ND control) CPB (ND + probiotic pool) DIOPF (HFD diabetic control) DIOPB (HFD + probiotic pool) | Mix of Lactobacillus rhamnosus, Lactobacillus acidophilus, Bifidobacterium bifidumi 6 × 10^8 CFU each | Insulin and glucose AUC after an IPGTT and glucose infusion rate during hyperinsulinemic euglycemic clamp | Submitted to IPGTT, DIOPB (HFD + probiotics) animals had better glucose and insulin profiles than DIOPF (HFD control). DIOPF group exhibited a greater reduction in glucose infusion rate compared to control animals. Also, probiotic treatment partially restored insulin sensitivity in DIOPF. Probiotic administration did not change any parameter of normal-fed animals. | Probiotics recovered intestinal permeability, LPS translocation, systemic low-grade inflammation and induced an improvement in hypothalamic insulin and leptin resistance. |
Zhang et al. [27] 2018, China | 4 weeks Groups: NC (ND control) NH (normal high-dose—5 × 10^8 live A. muciniphila) DC (HFD diabetic control) DH (diabetic high-dose-5 × 10^8 live A. muciniphila) DL (diabetic low-dose-5 × 10^6 live A. muciniphila) DP (diabetic-5 × 10^8 pasteurized A. muciniphila) DM (HFD diabetic metformin) | Akkermansia muciniphila 5 × 10^8 live CFU or 5 × 10^6 live CFU or 5 × 10^8 pasteurized CFU | Insulin and glucose AUC after OGTT | NC groups showed milder fluctuations and lower glycemic peak than HFD groups (p < 0.001). No significant difference in insulin and glucose values was observed between the HFD probiotic groups during OGTT; only metformin group had a lower glycemic peak than control (p < 0.05). | All diabetic groups treated had significantly lower hepatic glycogen and TNF-α levels, while DL, DP and DM groups also had significantly lower levels of LPS, MDA, plasminogen activator inhibitor-1 and GLP-1. DC, DP and DM groups had significantly higher triglycerides levels, DM group higher total cholesterol levels, and all diabetic treated groups had significantly higher HDL-c levels. |
Lee et al. [7] 2018, Korea | 5 weeks Groups: control (ND control) HFD (HFD diabetic control) HFD + Ln4 (HFD diabetic + L. plantarum Ln4) | Lactobacillus plantarum Ln4 5 × 10^8 CFU | Fasting insulin, HOMA-IR, AUC after OGTT and glucose tolerance during ITT | Insulin levels decreased significantly in groups treated with probiotic which induced a 40.6% reduction of the increased HOMA-IR value induced by HFD feeding. AUCs obtained from OGTT and ITT reduced significantly. | Ln4 administration strongly attenuated weight gain and reduced levels of triglycerides and adipokines, C-reactive protein, insulin-like growth factor binding protein-3, leptin, lipocalin-2 and MCP-1. Also, it regulated hepatic expression of insulin receptor substrate 2, serine/threonine-protein kinase and AMP-activated protein kinase and improved expression of lipoprotein lipase. |
Kikuchi et al. [40] 2018, Japan | 4 weeks Groups: Chow-Ct (ND control) Chow-400 (ND + probiotic 400 mg/kg dose) HFD-Ct (HFD diabetic control) HFD-200 (HFD + probiotic 200 mg/kg dose) HFD-400 (HFD + probiotic 400 mg/kg dose) | Bifidobacterium longum BR-108 sterilized 200 mg/kg or 400 mg/kg | Insulin AUC after OGTT and glucose AUC after ITT | AUCs obtained from OGTT and ITT showed improvement in insulin resistance and glucose tolerance (p < 0.05) in both, HFD-200 and HFD-400 groups after probiotic treatment. In other groups no significant difference was found. | Supplements of sterilized bacterial cells reduced weight gain, epididymal body fat mass, cholesterol and triglycerides levels, circulating lipopolysaccharides and liver triglycerides and had beneficial effects in intestinal microbiota. |
Natividad et al. [21] 2018, France | 4 weeks Groups: CD (ND control) HFD (HFD diabetic control—low B.wadsworthia) HFD Bw + (HFD + B. wadsworthia) HFD Bw + Lr + (HFD + B. wadsworthia + L. rhamnosus) | Lactobacillus rhamnosus CNCM I-3690 10^9 CFU | Fasting insulin, HOMA-IR and AUC after OGTT | Probiotic induced significant reductions in fasting plasma glucose, insulin and HOMA-IR. AUC obtained by OGTT further revealed that HFD Bw + Lr (mice with abundance of B. wadsworthia and treated with probiotic) tended (p = 0.058) to show a better glycemic control than HFD Bw + . | B. wadsworthia synergizes with HFD worsening systemic and mucosal inflammation. The probiotic intervention showed that it can be at least partly reversed by L. rhamnosus, which was associated with increased butyrate and propionate levels. |
Niibo et al. [35] 2018, Japan | 3 weeks Groups: Control (HFD diabetic control) LG2055 (HFD + probiotic) | Lactobacillus gasseri SBT 2055 (LG2055) 6 × 10^7 CFU | Fasting insulin and in response to OGTT | Both, fasting insulin and in response to OGTT, did not differ between groups. However, in diabetic animals, probiotic administration improved insulin secretion by attenuating inflammation. | Probiotic intervention increased HDL-c, C-peptide, liver glycogen and total SCFA content and decreased inflammatory cytokine levels. Also, higher expressions of insulin genes and insulin promoter factor 1 were found. |
Thiennimitr et al. [8] 2018, Thailand | 12 weeks Groups: ND (ND control) HFD (diabetic control) HFD L.paracasei (HFD + probiotic) HFD XOS (HFD + prebiotic) HFD HII01 + XOS (HFD + synbiotic) | Lactobacillus paracasei HII01 10^8 CFU | Fasting insulin, HOMA-IR and AUC after OGTT | Groups supplemented with probiotic improved insulin sensitivity as indicated by decreased insulin, HOMA-IR and plasma glucose AUC (p < 0.05). | Probiotic treated group improved lipid profile, attenuated dyslipidemia as indicated by decreased total and LDL-cholesterol levels. Also, a decrease in Firmicutes-to-Bacteroidetes ratio was observed. |
Chunchai et al. [37] 2018, Thailand | 12 weeks Groups: NDV (ND control) NDPE (ND control + prebiotic) NDPO (ND control + probiotic) NDC (ND control + synbiotic) HFV (HFD diabetic control) HFPE (HFD + prebiotic) HFPO (HFD + probiotic) HFC (HFD + synbiotic) | Lactobacillus paracasei HII01 10^8 CFU | Fasting insulin, HOMA-IR and AUC after OGTT | In treated groups, insulin level, HOMA-IR and the AUC after OGTT decreased significantly (p < 0.05). | All supplemented groups restored gut and systemic inflammation, cognition function through gut-brain axis, with improved hippocampal plasticity and attenuated brain mitochondrial dysfunction. Hippocampal oxidative stress and apoptosis were significantly decreased, as well as microglial activation leading to restored cognitive function. Lipid parameters (total cholesterol and LDL-c) were also improved. |
Morshedi et al. [38] 2018, Iran | 8 weeks Groups: HC (ND control) DC (HFD diabetic control) DL (HFD diabetic + probiotic) DI (HFD diabetic + prebiotic) DLI (HFD diabetic + synbiotic) DSh (HFD diabetic sham) | Lactobacillus plantarum ATCC 8014 10^7 CFU | Serum insulin | Insulin level increased in the probiotic group compared to the DSh group (p = 0.013), without difference among the supplemented ones (DL, DI, DLI). | LC group had lower plasma glucose, HbA1c, leptin, TNF-α, IL-6, LDL-c and and higher HDL-c levels. Probiotic treatment increased expressions of phosphatidylinositol-3-kinase and glycogen synthase genes and decreased of glycogen synthase kinase 3 beta mRNA. Pancreas histology showed recovery of islets cells. Also, improved SCFA production and decreased Firmicutes-to-Bacteroidetes ratio were observed. |
Wanchai et al. [36] 2018, Thailand | 12 weeks Groups: ND (ND control) NDL (ND + probiotic) HF (diabetic control) HFL (HFD + probiotic) | Lactobacillus paracasei HII01 10^8 CFU | Fasting insulin, HOMA-IR and response to OGTT | Insulin level and HOMA-IR were reduced significantly following probiotic supplementation, as well as plasma glucose levels during OGTT (p < 0.05). | Probiotic supplementation diminished hyperlipidemia (triglycerides and LDL-c) and systemic and kidney inflammation, endoplasmic reticulum stress and apoptosis, leading to a better kidney function. This reduced LPS levels, phosphorylation of NF-kB and c-Jun N-terminal kinase and expressions of TNF-α, IL-6, IL-1B and MCP-1 genes and ameliorated phosphoenolpyruvate carboxykinase expression. |
Natividad et al. [30] 2018, France | 12 weeks Groups: CD MRS (ND control) CD L. reuteri (ND + probiotic) HFD MRS (HFD diabetic control) HFD L. reuteri (HFD + probiotic) | Lactobacillus reuteri CNCM I 5022-10^9 CFU | Fasting insulin, HOMA-IR, AUC after OGTT and glucose tolerance during ITT | The HFD L. reuteri group improved HOMA-IR and glucose clearance and showed a better insulin sensitivity than the non-supplemented mice. | Probiotic group improved liver steatosis, alanine aminotransferase and triglycerides concentrations, intestinal barrier function and restored GLP-1 secretion. |
Yao et al. [39] 2019, China | 16 weeks Groups: ND (ND control) HFD (HFD diabetic control) L (HFD + N1115) FOS (HFD + FOS) Synbiotics (HFD + FOS + L) | Lactobacillus paracasei N1115 2.2 × 10^9 CFU | Fasting insulin, HOMA-IR and AUC after IPGTT | In the 3 supplemented groups, insulin levels and HOMA-IR returned to baseline values and the glucose AUC after IPGTT was improved. | Alterations in inflammatory pathways (TLR4, NF-κB, p38 MAPK) and expression of tight junctions’ proteins (occludin-1 and claudin-1) were restored mainly in the synbiotic-treated animals. Treated groups showed improvements in lipid profile, serum and hepatic TNF-α, IL-1B and monoamine oxidase, postponing cirrhosis. |
Additional findings obtained with single-strain probiotics
Lactobacillus
Bifidobacterium
Akkermansia muciniphila
Clostridium
Additional findings obtained with multiple-strains probiotics
Clinical trials
References | Study design | Participants’ characteristics | Protocol and groups | Probiotic and dose | Insulin resistance parameter | Effects on glucose metabolism | Other outcomes |
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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. |