Probiotic co-supplementation with absorbent smectite for pancreatic beta-cell function in type 2 diabetes: a secondary-data analysis of a randomized double-blind controlled trials.

Introduction: There is growing evidence from animal and clinical studies suggesting probiotics can positively affect type 2 diabetes (T2D). In a previous randomized clinical study, we found that administering a live multistrain probiotic and absorbent smectite once a day for eight weeks to patients with T2D could reduce chronic systemic inflammatory state, insulin resistance, waist circumference and improve the glycemic profile. However, there is a lack of evidence supporting the efficacy of probiotic co-supplementation with absorbent smectite on pancreatic ß-cell function in T2D. Aim: This secondary analysis aimed to assess the effectiveness of an alive multistrain probiotic co-supplementation with absorbent smectite vs placebo on ß-cell function in T2D patients. Material and methods: We performed a secondary analysis on a previously published randomized controlled trial (NCT04293731, NCT03614039) involving 46 patients with T2D. The main inclusion criteria were the presence of ß-cell dysfunction (%B<60%) and insulin therapy alone or combined with oral anti-diabetic drugs. The primary outcome was assessing ß-cell function as change C-peptide and %B. Results: We observed only a tendency for improving ß-cell function (44.22 ± 12.80 vs 55.69 ± 25.75; р=0.094). The effectiveness of the therapy probiotic-smectite group was confirmed by fasting glycemia decreased by 14% (p=0.019), HbA1c - 5% (p=0.007), HOMA-2 - 17% (p=0.003) and increase of insulin sensitivity by 23% (p=0.005). Analysis of the cytokine profile showed that statistical differences after treatment were in the concentration of both pro-inflammatory cytokines: IL-1ß (22.83 ± 9.04 vs 19.03 ± 5.57; p=0.045) and TNF-α (31.25 ± 11.32 vs 26.23 ± 10.13; p=0.041). Conclusion: Adding a live multistrain probiotic and absorbent smectite supplement slightly improved ß-cell function and reduced glycemic-related parameters in patients with T2D. This suggests that adjusting the gut microbiota could be a promising treatment for diabetes and warrants further investigation through more extensive studies.

Probiotic for Pancreatic ß-Cell Function in Type 2 Diabetes: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

INTRODUCTION: Many clinical studies have proved the effectiveness of probiotics in metabolic disorders associated with insulin resistance. However, the impact of probiotic therapy on pancreatic ß-cell function is ambiguous. The influence of probiotic supplementation vs. placebo on ß-cell function in people with type 2 diabetes (T2D) was assessed in a double-blind, single-center, randomized, placebo-controlled trial (RCT). METHODS: Sixty-eight patients with T2D were selected for participation in the RCT. Patients were randomly allocated to consumption of live multistrain probiotics or a placebo for 8 weeks, administered as a sachet formulation in double-blind treatment. The primary main outcome was the assessment of ß-cell function as change in C-peptide and HOMA-ß (homeostasis model assessment-estimated ß-cell function), which was calculated using the HOMA2 calculator (Diabetes Trials Unit, University of Oxford). Secondary outcomes were the changes in glycemic control-related parameters, anthropomorphic variables, and cytokines levels. Analysis of covariance was used to assess the difference between groups. RESULTS: Supplementation with live multiprobiotic was associated with slight significant improvement of ß-cell function (HOMA-ß increased from 32.48 ± 13.12 to 45.71 ± 25.18; p = 0.003) and reduction of fasting glucose level (13.03 ± 3.46 vs 10.66 ± 2.63 mmol/L and 234.63 ± 62.36 vs 192.07 ± 47.46 mg/dL; p < 0.001) and HbA1c (8.86 ± 1.28 vs 8.48 ± 1.22; p = 0.043) as compared to placebo. Probiotic therapy significantly affects chronic systemic inflammation in people with T2D by reducing pro-inflammatory cytokine levels. CONCLUSIONS: Probiotic therapies modestly improved ß-cell function in patients with T2D. Modulating the gut microbiota represents a new diabetes treatment and should be tested in more extensive studies. TRIAL REGISTRATION: NCT05765292.

Metabolic Benefits of Probiotic Combination with Absorbent Smectite in type 2 Diabetes Patients a Randomised Controlled Trial.

BACKGROUND: Numerous non-drug therapies have emerged in recent years for the prevention and improvement of type 2 diabetes (T2D). However, therapies based on dietary modification and/or microbiota may replace a large part of drug therapies in the coming years. AIM: The aim of the current study was to conduct placebo-controlled randomize clinical trial for the efficiency of a combination of multiprobiotics with smectite absorbent gel (Symbiter-Forte formulation) as an adjunction to the standard anti-diabetic therapy. METHODS: A total of 55 patients met the criteria and were included in double-blind single center RCT, to receive "Symbiter-Smectite" or placebo for 8-weeks administered as a sachet formulation. The primary outcome was the change in HOMA2-IR and insulin sensitivity (% S). Secondary outcomes were glycemic control parameters, ß-cells functional activity, anthropometric parameters and markers of a chronic systemic inflammatory response. RESULTS: Combined use of the probiotic mixture with smectite leads to a significant reduction in HOMA2-IR (3.14±0.97 vs 2.79±0.85; р=0.009) and improvement in % S (34.65±9.92 vs 39.42±12.78; p=0.011) after 8 weeks of the treatment period. Simultaneously, in the secondary outcome analysis lowering of HbA1c, waist circumference but not BMI and pro-inflammatory cytokines IL-1ß (p=0.004), TNF-α (p=0.008), IL-6 (p=0.005) and IL-8 (p=0.042) were detected. In placebo group, changes were insignificant. CONCLUSION: Probiotic with smectite due to its absorbent activity and stabilization mucus layer properties can impact the synergistic enhancement of a single effect, which manifested with a significant reduction in IR, waist circumference, markers of chronic systemic inflammation and improvement of glycemic profile as compared to placebo.

Vitamin D3 deficiency is associated with more severe insulin resistance and metformin use in patients with type 2 diabetes.

BACKGROUND: Vitamin D3 (vit. D3) deficiency is considered as one of the main factors involved in the development of type 2 diabetes (T2D). We assessed insulin resistance (IR), ß-cell functional activity and metabolic profile according to 25(OH) vit. D3 status in patients with T2D. METHODS: The study included 109 patients with T2D, divided in 3 groups: group 1 (N.=11) with normal levels of vit. D3 (>30 ng/mL); group 2 (N.=38) with vit. D3 insufficiency (21-29 ng/mL); and group 3 (N.=60) with vit. D3 deficiency (<20 ng/mL). IR and ß-cell functional activity were assessed as change in C-peptide concentration and homeostasis model assessment-estimated (HOMA) ß-cell function which was calculated using HOMA2 calculator. RESULTS: Patients with vit. D3 deficiency presented significantly higher C-peptide concentration compared to other groups. HOMA2 (3.29±1.89 vs. 2.12±0.71; P=0.049) and hemoglobin (H8b)A1c (9.11±1.63 vs. 7.75±1.06; P=0.016) levels changed significantly only in patients with vit. D3 deficiency compared to diabetics with normal vit. D3 levels. Furthermore, in univariate Pearson's correlation analysis, we observed significant association between vit. D3 levels and C-peptide, insulin sensitivity, HOMA2, triglyceride-glucose index, HbA1c and Body Mass Index, only in the vit. D3 deficiency group. In multivariate logistic regression analysis, poor glycemic control, as defined by HbA1c levels, was independent from metformin use while high density lipoprotein-cholesterol levels were associated with vit. D3 deficiency. CONCLUSIONS: Our study demonstrated that vit. D3 deficiency in patients with T2D was associated with more severe IR, poor glycemic control and obesity compared to normal status or vit. D3 insufficiency.

New insights on strain-specific impacts of probiotics on insulin resistance: evidence from animal study.

BACKGROUND AND AIMS: сomparative animal study of effectiveness of intermittent administration of lyophilized single-, three- and alive multistrain probiotic in short courses on insulin resistance (IR) in rats with experimental obesity. METHODS: 70 rats were divided into 7 groups (n = 10 in each). Rats of group I were left intact. Newborn rats in groups II-VII were administered monosodium glutamate (MSG) (4 mg/g) by injection. Rats in group II (MSG-obesity group) were left untreated. The rats in groups III-V received lyophilized mono-probiotics B.animalis VKL, B.animalis VKB, L.casei IMVB-7280 respectively. The rats in group VI received all three of these probiotic strains mixed together. Group VII was treated with multi-probiotic "Symbiter", containing 14 different live probiotic strains (Lactobacillus, Bifidobacterium, Propionibacterium, Acetobacter genera). RESULTS: Treatment of newborn rats with MSG lead to the development of obesity in all MSG-obesity rats and up to 20-70% after probiotic administration. Additions to probiotic composition, with preference to alive strains (group VII), led to significantly lower rates of obesity, decrease in HOMA-IR (p < 0.001), proinflammatory cytokines levels - IL-1ß (p = 0.003), IL-12Bp40 (p < 0.001) and elevation of adiponectin (p = 0.003), TGF-ß (p = 0.010) in comparison with MSG-obesity group. Analysis of results in groups treated with single-strain probiotics (groups III-V) shows significant decrease in HOMA-IR, but changes were less pronounced as compared to mixture groups and did not achieve intact rats level. Other metabolic parameters were not affected significantly by single strains. CONCLUSION: Our findings provide major clues for how to design and use probiotics with more efficient compositions in obesity and IR management and may bring new insights into how host-microbe interactions contribute to such protective effects.

Neuropathic diabetic foot ulcers treated with cerium dioxide nanoparticles: A case report.

Wound healing in diabetes is frequently impaired and its treatment remains a challenge. The ability of topical application of cerium (Ce) dioxide nanoparticles (CNPs) to accelerate wound healing in an animal model provides a rationale to develop this technology for use in humans affected by traumatic injury, diabetes and burns. We first described a case report of successful topical treatment of neuropathic diabetic foot ulcers with novel gel containing CNPs. The CNPs has bacteriostatic activity, anti-inflammatory properties and can penetrated into the wound tissue and reduced oxidative damage therefore protect regenerative tissue, suggesting a therapeutic potential for topical treatment of diabetic foot ulcers.

Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study.

BACKGROUND: The manipulation of gut microbiota via administration of probiotics has been proposed as a potential strategy for the treatment of non-alcoholic fatty liver disease (NAFLD). Hence, we performed a double-blind single center randomized placebo-controlled trial (RCT) to evaluate the efficacy of coadministration of probiotics with omega-3 vs. placebo in type-2 diabetic patients with NAFLD. METHODS: A total of 48 patients met the criteria for inclusion. They were randomly assigned to receive "Symbiter Omega" combination of probiotic biomass supplemented with flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5%) or placebo for 8-weeks. The primary main outcomes were the change in fatty liver index (FLI) and liver stiffness (LS) measured by Shear Wave Elastography (SWE). Secondary outcomes were the changes in transaminases level, serum lipids and cytokines levels. RESULTS: In probiotic-omega group, FLI significantly decreased from 83.53±2.60 to 76.26±2.96 (P<0.001) while no significant changes were observed in the placebo group (82.86±2.45 to 81.09±2.84; P=0.156). Changes of LS in both groups were insignificant. Analysis of secondary outcomes showed that the coadministration of probiotics with omega-3 lead to significant reduction of serum gamma-glutamyl transpeptidase, triglycerides, and total cholesterol. Chronic systemic inflammatory markers after intervention decrease significantly only in Symbiter Omega group: IL-1ß (P=0.029), TNF-α (P<0.001), IL-8 (P=0.029), IL-6 (P=0.003), and INF-γ (P=0.016). CONCLUSIONS: Coadministration of a live multi-strain probiotic mixture with omega-3 fatty acids once daily for 8 weeks to patients with NAFLD can reduce liver fat, improve serum lipids, metabolic profile, and reduce chronic systemic inflammatory state.

Effect of alive probiotic on insulin resistance in type 2 diabetes patients: Randomized clinical trial.

BACKGROUND: Probiotics have beneficial effect on obesity related disorders in animal models. Despite a large number of animal data, randomized placebo-controlled trials (RCT) concluded that probiotics have a moderate effect on glycemic control-related parameters. However, effect of probiotics on insulin resistance are inconsistent. AIM: In a double-blind single center RCT, effect of alive multistrain probiotic vs. placebo on insulin resistance in type 2 diabetes patient were assessed. METHODS: A total of 53 patients met the criteria for inclusion. They were randomly assigned to receive multiprobiotic "Symbiter" (concentrated biomass of 14 probiotic bacteria genera Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium) or placebo for 8-weeks administered as a sachet formulation. The primary main outcome was the change HOMA-IR (homeostasis model assessment-estimated insulin resistance) which calculated using Matthews et al.'s equation. Secondary outcomes were the changes in glycemic control-related parameters, anthropomorphic variables and cytokines. RESULTS: Supplementation with alive multiprobiotic for 8 weeks was associated with significant reduction of HOMA-IR from 6.85 ±â€¯0.76 to 5.13 ±â€¯0.49 (p = 0.047), but remained static in the placebo group. With respect to our secondary outcomes, HbA1c insignificant decreased by 0.09% (p = 0.383) and 0.24% (p = 0.068) respectively in placebo and probiotics groups. However, in probiotic responders (n = 22, patient with decrease in HOMA-IR) after supplementation a significant reduction in HbA1c by 0.39% (p = 0.022) as compared to non-responders was observed. In addition, from markers of chronic systemic inflammatory state only TNF-α and IL-1ß changes significantly after treatment with probiotics. CONCLUSION: Probiotic therapies modestly improved insulin resistance in patients with type 2 diabetes.

A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial.

BACKGROUND: Probiotics have a beneficial effect on nonalcoholic fatty liver disease (NAFLD) in animal models. Randomized placebo-controlled trials (RCTs) in NAFLD are still lacking in humans despite a large number of data from animal research. AIM: We performed a double-blind single center RCT of live multi-strain probiotic vs. placebo in type 2 diabetes patients with NAFLD. METHODS: A total of 58 patients met the criteria for inclusion. They were randomly assigned to receive the multi-probiotic "Symbiter" (concentrated biomass of 14 probiotic bacteria genera Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium) or placebo for 8-weeks administered as a sachet formulation in double-blind treatment. The primary main outcomes were the changes in fatty liver index (FLI) and liver stiffness (LS) measured by Shear Wave Elastography (SWE). Secondary outcomes were the changes in aminotransferase activity, serum lipids and cytokines (TNF-α, IL-1ß, IL-6, IL-8, and IFN-γ) levels. Analysis of covariance was used to assess the difference between groups. RESULTS: In the probiotic group, FLI significantly decreased from 84.33+/-2.23 to 78.73+/-2.58 (p<0.001) but it did not change in the placebo group (82.57+/-2.45 to 81.6 +/-2.36; p=0.367). In both groups a slight but not significant reduction of LS measured by SWE was detected. Analysis of the secondary outcomes showed that probiotics reduced the level of serum AST and GGT. Among the markers of chronic systemic inflammatory state, only TNF-α and IL-6 levels changed significantly after the treatment with the probiotic. CONCLUSION: The probiotic "Symbiter" reduces liver fat, aminotransferase activity, and the TNF-α and IL-6 levels in NAFLD patients. Modulation of the gut microbiota might represent a new therapy for NAFLD, which should be tested in larger studies.