Effect of a Probiotic Supplement on Gut Microbiota and Glycemic Control in Patients With Type 1 Diabetes (PRODIAB)

This randomized, double-blind clinical trial aims to evaluate the impact of a nutritional supplement composed of inulin (prebiotic) and tyndallized probiotics (paraprobiotics) on gut microbiota composition, intestinal barrier integrity, and glycemic control in individuals with type 1 diabetes mellitus (T1D). A total of 80 participants will be recruited: 40 with T1D and 40 healthy controls. Each group will be randomly assigned to receive either the active supplement or a placebo for a period of approximately 98 days.

The study will include pre- and post-intervention assessments using stool samples (for microbiota analysis and intestinal inflammation markers like zonulin and calprotectin), continuous glucose monitor (CGM) data, blood tests (for glycemic, hepatic, renal, and lipid profiles), body composition analysis by bioimpedance (including phase angle), and validated questionnaires assessing gastrointestinal symptoms, lifestyle, dietary intake, and diabetes-related quality of life.

The main objectives are to analyze changes in gut microbiota diversity and composition, assess effects on intestinal permeability and inflammation, evaluate the safety and tolerability of the supplement, and determine its impact on metabolic markers such as fasting glucose, HbA1c, glycemic variability, and HOMA-IR.

This project seeks to explore microbiota modulation as a potential complementary therapeutic strategy for improving glycemic control and metabolic health in individuals with T1D. The supplement will be provided in 10 mL gel sticks, containing 4000 mg of inulin and 1000 mg of tyndallized probiotics, taken once daily. The intervention period has been strategically planned to avoid holidays and vacation times to ensure adherence and minimize lifestyle variability.

Participants with type 1 diabetes mellitus will receive a daily 10 mL gel supplement containing 4000 mg of inulin and 1000 mg of tyndallized probiotics for approximately 98 days. The supplement is designed to modulate gut microbiota and improve glycemic control.

Dietary Supplement: Probiotic/Prebiotic Supplement

Participants with type 1 diabetes mellitus will receive a daily 10 mL placebo gel without active ingredients for approximately 98 days. The placebo is organoleptically identical to the supplement to maintain blinding.

Dietary Supplement: Placebo Gel

Healthy participants will receive a daily 10 mL gel supplement containing 4000 mg of inulin and 1000 mg of tyndallized probiotics for approximately 98 days. This arm allows comparison of microbiota and metabolic responses between diabetic and non-diabetic individuals.

Dietary Supplement: Probiotic/Prebiotic Supplement

Healthy participants will receive a daily 10 mL placebo gel without active ingredients for approximately 98 days. The placebo is identical in appearance and flavor to the active supplement.

Dietary Supplement: Placebo Gel

Oral dietary supplement in gel form (10 mL per day) containing 4000 mg of inulin and 1000 mg of tyndallized probiotics. Administered once daily for approximately 98 consecutive days. Produced by Martínez Nieto S.A. (MARNYS®). Intended to modulate gut microbiota and improve glycemic and inflammatory markers.

Oral placebo in gel form (10 mL per day), identical in appearance, texture, and taste to the active supplement, but without probiotic or prebiotic components. Administered once daily for 98 days to maintain blinding and control effects.

Plazo: Baseline and 98 days post-intervention

Variation in the relative abundance and diversity of gut microbiota species assessed by 16S rRNA sequencing from stool samples collected at baseline and after 98 days of intervention.

Plazo: Baseline and 98 days post-intervention

Assessment of changes in fasting glucose levels (mg/dL) via blood test.

Plazo: Baseline and 98 days post-intervention

Assessment of changes in glycated hemoglobin levels (HbA1c, %) via blood test.

Plazo: Baseline and 98 days post-intervention

Assessment of changes in fasting insulin levels via blood test. μU/mL

Plazo: Baseline and 98 days post-intervention

Assessment of changes in insulin resistance estimated using the HOMA-IR index.

Plazo: Baseline and 98 days post-intervention

Assessment of the percentage of time that glucose levels are within the target range using continuous glucose monitoring (CGM).

Plazo: Baseline and 98 days post-intervention

Assessment of the percentage of time with hyperglycemia using CGM.

Plazo: Baseline and 98 days post-intervention

Assessment of the percentage of time with hypoglycemia using CGM.

Plazo: Baseline and 98 days post-intervention

Assessment of average glucose concentration (mg/dL) using CGM.

Plazo: Baseline and 98 days post-intervention

Assessment of glucose coefficient of variation (%) using CGM.

Plazo: Baseline and 98 days post-intervention

Zonulin levels will be measured in fasting plasma samples using ELISA at baseline and after the intervention (ng/mL).

Plazo: Baseline and 98 days post-intervention

Calprotectin levels will be measured in stool samples using immunoassay at baseline and after the intervention (µg/g).

Impact of a Probiotic Supplement on Gut Microbiota and Glycemic Control in Patients With Type 1 Diabetes Mellitus: A Randomized Double-Blind Clinical Trial