To Evaluate the Beneficial Effect of Probiotics on DKD Patients and the Role of Gut Microbiota Modulation

To Evaluate the Beneficial Effect of Probiotics on DKD Patients and the Role of Gut Microbiota Modulation

To evaluate the efficacy of probiotics in the treatment of diabetic kidney disease, this study is designed to explore after consumption of probiotics lactobacillus reuteri ADR-1 and lactobacillus rhamnosus GM-020 composite strain powder sachets for 6 months, whether the improvement of blood sugar, kidney related indicators can further improve the course of diabetic kidney disease. The clinical trial predicted that probiotics can improve diabetic kidney disease by changing the intestinal flora by inhibiting harmful bacteria, reduction of systemic oxidative stress, balance carbohydrate and fat metabolism, further preventing the progress of diabetic kidney disease.

WHO predicts that diabetes will become the seventh leading cause of death in 2030. This disease usually causes complications including hypertension, diabetic kidney disease, neuropathy, skin infection, and a high risk of blindness and so on. It demonstrated that probiotics have beneficial effects on several disorders; these beneficial effects include a reduction in allergic symptoms, a decrease in serum cholesterol levels, the prevention of obesity, and an improvement of the digestive system. In recent years, many studies have pointed out that Lactobacillus affects the progression of diabetes kidney disease by controlling blood sugar. From 2017 to 2020, 8 clinical trials conducted related research to explore the clinical benefits of probiotics on diabetic kidney disease. It was found that the indicators related to kidney function have ameliorated significantly, including improving glomerular function, blood sugar control, insulin metabolism, inflammatory substances in serum, and even oxidative stress factors, etc. In a previous study, Lactobacillus strain ADR-1 was selected to verify the efficacy by utilizing HFD (High-fructose-fed) rats model, the result shows reductions in serum HbA1c and liver injury after oral gavage for 14 weeks. Afterward, a double-blind, randomized, placebo-group human clinical trial was conducted, recruiting 68 subjects with type 2 diabetes to evaluate the intestinal flora and blood sugar-related indicators, among which the metabolic indicators had significant changes. After taking it for 3 and 6 months, HbA1c and cholesterol were significantly reduced compared to the Placebo group, it was also found that the L.reuteri flora had a significant increase in the intestinal flora while the same pattern was found in the Bifidobacterium flora accordingly. This result represents the development of a positive correlation between Lactobacillus and Bifidobacterium for the intestinal flora. Furthermore, GM-020 has been proved by mouse model experiments to slow down kidney diseases, including the improvement of related indicators of renal function, serum urea nitrogen (BUN), and creatinine (Creatinine), and it shows dose-dependent variation. The combination of these two strains of probiotics is predicted to improve the metabolical index of diabetic kidney disease. This clinical trial will explore the health-promoting effect of probiotics on patients with diabetic kidney disease, and fully explore how probiotics can improve the good bacteria and reduce the bad bacteria by changing the intestinal flora to achieve anti-inflammatory effects, Chronic inflammation, reduce systemic oxidative stress, balances carbohydrate and fat metabolism, and prevents the progression of diabetic kidney disease.

Two-strain probiotic supplement includes Lactobacillus reuteri ADR-1 (alive) and Lactobacillus rhamnosus GM-020 ( alive).

Blood samples will be collected to examine the variation of Cys-C (Cystatin C) from baseline at 3 months.

The unit of measurement of blood pressure is mmHg. Both systolic and diastolic blood pressure will be measured.

The unit of measurement of blood pressure is mmHg. Both systolic and diastolic blood pressure will be measured.

Change from baseline in levels of HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) at 3-months

Change from baseline in levels of HOMA-β (Homeostatic Model Assessment for β-cell function) at 3-months

Change from baseline in levels of HOMA-β (Homeostatic Model Assessment for β-cell function) at 6-months

CG will be calculated with creatinine, age, weight, gender. The equation of CG = (((140 - age in years) x (weight in kg)) x 1.23) / (serum creatinine in micromol/l).

CG will be calculated with creatinine, age, weight, gender. The equation of CG = (((140 - age in years) x (weight in kg)) x 1.23) / (serum creatinine in micromol/l).

eGFR will be estimated according to the CKD-EPI Creatinine Equation (2021) which is calculated with serum creatinine, Cystatin C, age, gender.

eGFR will be estimated according to the CKD-EPI Creatinine Equation (2021) which is calculated with serum creatinine, Cystatin C, age, gender.

Blood samples will be collected to examine variation in TG (Triglyceride), TC (Total Cholesterol), VLDL (Very-Low-Density Lipoprotein), LDL (Low-density lipoprotein), HDL (High-density lipoprotein).

Blood samples will be collected to examine variation in TG (Triglyceride), TC (Total Cholesterol), VLDL (Very-Low-Density Lipoprotein), LDL (Low-density lipoprotein), HDL (High-density lipoprotein).

Blood samples will be collected to examine variation in hs-CRP (high-sensitivity C-reactive protein), IL-6 (Interleukin-6), IL-18 (Interleukin-18), IL -1-α (Interleukin-1-α), IL-1β (Interleukin-1 β), TNF-α (Tumor necrosis factor-α), NGAL (Neutrophil Gelatinase-Associated Lipocalin), sTNFR1 (Soluble tumour necrosis factor receptor-1), PGRN (Progranulin). All the indexes will be recorded in in pg/mL.

Blood samples will be collected to examine variation in hs-CRP, IL-6, IL-18, IL-1-α, IL-1β, TNF-α, NGAL, sTNFR1, PGRN. All the indexes will be recorded in in pg/mL.

TIBC will be calculated by summing the values of serum iron and UIBC(unsaturated iron-binding capacity) which is examed from blood samples.

TIBC will be calculated by summing the values of serum iron and UIBC which is examed from blood samples.

Change from baseline in self-record of the International physical activity questionary (IPAQ) in physical assessment at 6 months

The questionnaire will be recorded the laborious activity by the subject himself/herself before and after the treatment.

The analysis of Gut microbiota will utilize DNA sequencing to investigate the intestinal microbiota through stool samples.

Inclusion Criteria: Age between 25 and 80 years old Suffering from type 2 diabetes and stable medication for 3 months Detection of HbA1c before meals between 7% and 10% Stage 1-3a diabetic nephropathies (eGFR > 45 mL/min) Microalbuminuria estimated between 30 to 300 mg/day Exclusion Criteria: Patients with Type I Diabetes Mellius Patients with inflammatory bowel disease, liver disease, liver cirrhosis, systemic lupus erythematosus, malignancy, and high blood pressure. Patients with hypoglycemic coma, Diabetic ketoacidosis, hyperosmolar non-ketotic diabetic coma, or diabetes mellitus acute complications. Acute infection medical history in past 3 month Fasting blood glucose >13.3 mmol/L GPT>100U/L (2.5 times than usual situation) Vulnerable population (Including breeding or pregnant women, prisoner, aboriginal, disabled population) Smoker or Alcoholic Taking Antibiotics in past 1 month Stably taking probiotics supplements in past 1 months (Yogurt or dairy products were excluded) Taking immunosuppressive drug, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers in past 3 months