Understanding how pre- and probiotics affect the gut microbiome and metabolic health.

The gut microbiome, a complex assembly of microorganisms, significantly impacts human health by influencing nutrient absorption, the immune system, and disease response. These microorganisms form a dynamic ecosystem that is critical to maintaining overall well-being. Prebiotics and probiotics are pivotal in regulating gut microbiota composition. Prebiotics nourish beneficial bacteria and promote their growth, whereas probiotics help maintain balance within the microbiome. This intricate balance extends to several aspects of health, including maintaining the integrity of the gut barrier, regulating immune responses, and producing metabolites crucial for metabolic health. Dysbiosis, or an imbalance in the gut microbiota, has been linked to metabolic disorders such as type 2 diabetes, obesity, and cardiovascular disease. Impaired gut barrier function, endotoxemia, and low-grade inflammation are associated with toll-like receptors influencing proinflammatory pathways. Short-chain fatty acids derived from microbial fermentation modulate anti-inflammatory and immune system pathways. Prebiotics positively influence gut microbiota, whereas probiotics, especially Lactobacillus and Bifidobacterium strains, may improve metabolic outcomes, such as glycemic control in diabetes. It is important to consider strain-specific effects and study variability when interpreting these findings, highlighting the need for further research to optimize their therapeutic potential. The aim of this report is therefore to review the role of the gut microbiota in metabolic health and disease and the effects of prebiotics and probiotics on the gut microbiome and their therapeutic role, integrating a broad understanding of physiological mechanisms with a clinical perspective.

Neuromuscular electrical stimulation changes glucose, but not its variability in type 2 diabetes: a randomized clinical trial.

Neuromuscular electrical stimulation (NMES) can be an alternative to conventional exercising. This randomized clinical trial evaluated the effect of NMES in type 2 diabetes patients. Twenty-eight individuals with type 2 diabetes were assigned to NMES (n=14) or NMES-placebo (n=14) applied to knee extensor muscles for 60 minutes. Glucose variability, microvascular function and endothelial function were evaluated through continuous glucose monitoring system, near infrared spectroscopy and flow-mediated dilatation, respectively. Glucose levels (mg/dl) decreased 2h (184 ± 11 vs 223 ±15), 3h (179 ± 12 vs 219 ±14) and 4h (177 ± 12 vs 212 ±12) after NMES, in comparison to NMES-placebo. No differences in glucose variability were found: coefficient of variation (%) at 0-6h (11.4±1.3 vs 11.4±1.2), 6-12h (9.8±1.0 vs 11.6±1.6), 12-18h (15.5±2.0 vs 11.4±2.1), 18-24h (12.8±2.3 vs 10.0±1.6); standard deviation (mg/dl) at 0-6h (21.6±2 vs 24.6±3.5), 6-12h (19.5±1.8 vs 20.3±2.8), 12-18h (29.9±3.5 vs 21.3±2.8),18-24h (22.8±4.1 vs 16.6±2.0) and mean amplitude of glycemic excursions (mg/dl) 54.9±25.0 vs 70.3±35.7. Endothelial and microvascular functions did not change. In conclusion, one acute NMES session was strong enough to trigger glucose reduction in individuals with type 2 DM, but it failed to induce any significant change in glucose variability, endothelial and microvascular functions.

The effect of probiotics, prebiotics or synbiotics on metabolic outcomes in individuals with diabetes: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: The aim was to conduct a systematic review and meta-analysis of randomised controlled clinical trials assessing the effect of probiotic, prebiotic or synbiotic supplementation on gut microbiota and glucose control and lipid levels in individuals with diabetes. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched. The eligibility criteria for the studies was involvement of participants with a diagnosis of type 1 or type 2 diabetes. Metabolic outcomes (glucose control, insulinaemia, and lipid profile) of any probiotic, prebiotic or synbiotic supplementation related to modification of gut microbiota (prebiotics, probiotics and synbiotics) were analysed. We provided a narrative synthesis and meta-analysis of the findings on metabolic outcomes from the studies. Metabolic outcomes were extracted post-intervention and expressed as mean differences (MDs) and 95% CIs between treatment and comparator groups. We pooled the results using a random-effects meta-analysis. The meta-analysis was conducted using Review Manager (RevMan) software. RESULTS: After the removal of duplicates and ineligible studies, 5219 studies were retained for review of titles and abstracts. The number of articles was reduced to 130 by review, for which the full-text articles were obtained and reassessed, 38 of which were included in the final meta-analysis. Overall, the use of prebiotics, probiotics or synbiotics reduced HbA1c levels, but did not reach the threshold for significance (-2.17 mmol/mol, 95% CI -4.37, 0.03; p = 0.05, [-0.20%, 95% CI -0.40 to 0.00; p = 0.05, I2 = 66%]) and had no effect on LDL-cholesterol levels (-0.05 mmol/l; 95% CI -0.14, 0.05, p = 0.35, I2 = 37%). However, their consumption decreased levels of fasting blood glucose (-0.58 mmol/l; 95% CI -0.86, -0.30; p < 0.01, I2 = 60%), total cholesterol (-0.14 mmol/l; 95% CI -0.26, -0.02, p = 0.02, I2 = 39%), triacylglycerols (-0.11 mmol/l; 95% CI -0.20, -0.02, p = 0.01, I2= 21%) and insulinaemia (-10.51 pmol/l; 95% CI -16.68,-4.33, p < 0.01, I2 = 74%), and increased HDL-cholesterol levels (0.04 mmol/l; 95% CI 0.01, 0.07, p < 0.01, I2= 24%). CONCLUSIONS/INTERPRETATION: In individuals with diabetes mellitus, supplementation with probiotics, prebiotics or synbiotics improved metabolic variables, although the magnitude of this effect is low. Our results suggest that consumption of probiotics, prebiotics or synbiotics may be a potential adjuvant treatment for improving metabolic outcomes. REGISTRATION: PROSPERO ID CRD42017080071. Graphical abstract.

Inspiratory Muscle Training on Glucose Control in Diabetes: A Randomized Clinical Trial.

This study evaluated the effects of inspiratory muscle training (IMT) in glucose control and respiratory muscle function in patients with diabetes. It was a randomized clinical trial conducted at the Physiopathology Laboratory of the Hospital de Clínicas de Porto Alegre. Patients with Type 2 diabetes were randomly assigned to IMT or placebo-IMT (P-IMT), performed at 30% and 2% of maximal inspiratory pressure, respectively, every day for 12 weeks. The main outcome measures were HbA1c, glycemia, and respiratory muscle function. Thirty patients were included: 73.3% women, 59.6 ± 10.7 years old, HbA1c 8.7 ± 0.9% (71.6 ± 9.8 mmol/mol), and glycemia 181.8 ± 57.8 mg/dl (10.5 ± 3.2 mmol/L). At the end of the training, HbA1c was 8.2 ±0.3% (66.1 ± 3.3 mmol/mol) and 8.7 ± 0.3% (71.6 ± 3.3 mmol/mol) for the IMT and P-IMT groups, respectively (p = .8). Fasting glycemia decreased in both groups with no difference after training although it was lower in IMT at 8 weeks: 170.0 ± 11.4 mg/dl(9.4 ± 0.6 mmol/L) and 184.4 ± 15.0 mg/dl (10.2 ± 0.8 mmol/L) for IMT and P-IMT, respectively (p < .05). Respiratory endurance time improved in the IMT group (baseline = 325.9 ± 51.1 s and 305.0 ± 37.8 s; after 12 weeks = 441.1 ± 61.7 s and 250.7 ± 39.0 s for the IMT and P-IMT groups, respectively; p < .05). Considering that glucose control did not improve, IMT should not be used as an alternative to other types of exercise in diabetes. Higher exercise intensities or longer training periods might produce better results. The clinical trials identifier is NCT03191435.

Effects of grape juice consumption on muscle fatigue and oxidative stress in judo athletes: a randomized clinical trial.

Physiological levels of reactive oxygen species (ROS) are important for intracellular and extracellular redox regulation in signaling and defense processes. Strenuous exercise can also contribute to this imbalance, and the muscle fatigue, evidenced by impaired strength or power generation, can be caused by various reasons, including oxidative stress. Antioxidants can prevent the formation of ROS by intercepting free radicals. Twenty judo athletes were included in this randomized, double-blind clinical trial into grape juice and placebo groups, and they consumed grape juice or placebo daily for 14 days in a crossover model. The outcomes were analyzed before and after combat simulations. The upper limb strength was higher in the grape juice group than in the placebo (p [group] = 0.003). The lipid damage levels were 10% higher in the placebo group (p [interaction] = 0.048). During the pre-exercise, the placebo group showed 19% more DNA damage than the grape juice group. The superoxide dismutase activity was 80% lower in the grape juice group (p [interaction] < 0.001). The consumption of grape juice can improve parameters of oxidative stress by reducing the lipid and DNA damage.

Comparison of the effects of two antioxidant diets on oxidative stress markers in triathletes.

Intense exercise generates an imbalance in the redox system. However, chronic exercise can yield antioxidant adaptations. A few studies with humans have investigated the effects of antioxidant diets on athletes. Therefore we compared the effects of two dietary interventions on oxidative stress in competitive triathletes. Thirteen male triathletes were selected and divided into 2 groups: one that had a regular antioxidant diet (RE-diet) and the other that had a high antioxidant diet (AO-diet). The diet period was 14 days and blood samples were collected before and after this period. The AO-diet provided twice the dietary reference intake (DRI) of α-tocopherol (30 mg), five times the DRI of ascorbic acid (450 mg), and twice the DRI of vitamin A (1800 g), while the RE-diet provided the DRI of α-tocopherol (15 mg), twice the DRI of ascorbic acid (180 mg) and the DRI of vitamin A (900 µg). The oxidative stress parameters evaluated were: thiobarbituric acid reactive substances (TBARS), total reactive antioxidant potential (TRAP), total sulfhydryl, carbonyl, superoxide dismutase (SOD) activity, hydrogen peroxide consumption and glutathione peroxidase (GPx) activity. We observed, after the diet period, an increase in sulfhydryl, TRAP, TBARS and SOD activity, and a decrease in carbonyl levels. However, no changes were found in hydrogen peroxide consumption or GPx activity. We concluded that antioxidant-enriched diets can improve the redox status of triathletes.

The impact of dietary, surgical, and pharmacological interventions on gut microbiota in individuals with diabetes mellitus: A systematic review.

AIMS: To conduct a systematic review assessing the association between dietary, surgical, and pharmacological interventions and changes in the gut microbiota of individuals with diabetes. METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were searched focusing on the effects of dietary, bariatric surgery, and pharmacological interventions on gut microbiota in adults with diabetes. Studies were classified based on qualitative changes using a simple vote-counting method, evaluating reduction, no effect, or an increase in the gut microbiota outcomes. RESULTS: 6,004 studies were retained to review their titles and abstracts. A total of 149 full-text articles were reassessed, of which 49 were included in the final analysis. This review indicates that dietary, surgical, and pharmacological interventions increase or decrease bacterial populations from more than 60 families, genera, or species. In general, the interventions led to an increase in the bacterial population from phylum Firmicutes, mainly Lactobacillus species, compared to the gram-negative bacterial population from phylum Bacteroidetes. CONCLUSIONS: The results of the included studies suggest that interventions aimed at reducing species related to uncontrolled diabetes and increasing species related to the healthy gut are potential adjuvants in treating diabetes; however, well-conducted interventional studies targeting gut microbiota are necessary.

C-reactive protein and blood pressure variability in type 2 hypertensive diabetic patients.

OBJECTIVE: Increased blood pressure (BP) variability and inflammation are included among the factors recognized as potential predictors of cardiovascular events in type 2 diabetes and hypertension. This study aimed to evaluate whether C-reactive protein (CRP) is associated with increased BP variability in diabetic-hypertensive patients. PATIENTS AND METHODS: We carried out a cross-sectional study with 285 diabetic-hypertensive patients, evaluating laboratory characteristics and 24-h ambulatory BP monitoring. SD, coefficient of variation (CV%), time-rate index of 24-h systolic BP (SBP), and 24-h BP patterns were evaluated. Pearson's χ-test, Student's t-test, and the Mann-Whitney test were used to compare the groups. Groups were defined by CRP of up to 3 mg/l (low) and more than 3 mg/l (high). RESULTS: The age of the patients was 59 (54-62) years; 101 (35%) were men. There was an increase in office SBP [137 (127-148) vs. 145 (130-157) mmHg] and DBP [79 (73-86) vs. 82 (76-91) mmHg] in the high CRP group. Blood pressure variability indexes were not different among groups [SD: 11.2 (9-15) vs. 12.2 (10-15) mmHg; CV%: 8.6 (7-11) vs. 9.4 (7-12); time rate: 0.55±0.12 vs.12.2 (10-15) mmHg/min]. In addition, BMI (29.3±3.8 vs. 30.9±3.6 kg/m), total cholesterol [166 (148-190) vs. 177 (156-210) mg/dl], and HbA1c [7.5% (6.6-8.9) vs.8.3% (7.1-9.9)] were higher in the high CRP group. CONCLUSION: In patients with diabetes and hypertension, higher CRP levels are linked to cardiometabolic derangements, although they are not associated with increased BP variability.

LipoCardium: endothelium-directed cyclopentenone prostaglandin-based liposome formulation that completely reverses atherosclerotic lesions.

Atherosclerosis is a multifactorial inflammatory disease of blood vessels which decimates one in every three people in industrialized world. Despite the important newest clinical approaches, currently available strategies (e.g. nutritional, pharmacological and surgical) may only restrain the worsening of vascular disease. Since antiproliferative cyclopentenone prostaglandins (CP-PGs) are powerful anti-inflammatory agents, we developed a negatively charged liposome-based pharmaceutical formulation (LipoCardium) that specifically direct CP-PGs towards the injured arterial wall cells of atherosclerotic mice. In the blood stream, LipoCardium delivers its CP-PG contents only into activated arterial wall lining cells due to the presence of antibodies raised against vascular cell adhesion molecule-1 (VCAM-1), which is strongly expressed upon inflammation by endothelial cells and macrophage-foam cells as well. After 4 months in a high-lipid diet, all low-density lipoprotein receptor-deficient adult control mice died from myocardium infarction or stroke in less than 2 weeks, whereas LipoCardium-treated (2 weeks) animals (still under high-lipid diet) completely recovered from vascular injuries. In vitro studies using macrophage-foam cells suggested a tetravalent pattern for LipoCardium action: anti-inflammatory, antiproliferative (and pro-apoptotic only to foam cells), antilipogenic and cytoprotector (via heat-shock protein induction). These astonishing cellular effects were accompanied by a marked reduction in arterial wall thickness, neointimal hyperplasia and lipid accumulation, while guaranteed lifespan to be extended to the elderly age. Our findings suggest that LipoCardium may be safely tested in humans in a near future and may have conceptual implications in atherosclerosis therapy.