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The goal of this study is to evaluate the efficacy of metformin on insulin sensitivity and vascular endothelial function with respect to gut microbiota and metabolome in women with established insulin resistance and its tolerance after 12 weeks of probiotic therapy.
The hypothesis is probiotic therapy in women with established insulin resistance undergoing metformin treatment increases the drug's efficacy to improve insulin sensitivity and intestinal endothelial function, and reduces gastrointestinal side effects.
Study participants will be randomly assigned to 2 groups, taking a probiotic (GS) or a placebo (GP). The randomization scheme will be computer-generated using permuted blocks of block size 4.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| the group GS | Experimental | probiotic treatment group, ca. 20 participants |
|
| the group GP | Placebo Comparator | placebo group, ca. 20 participants |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| the group GS (probiotic) | Dietary Supplement | The probiotic-supplemented group will receive 2 capsules of freeze-dried powder of a probiotic mixture containing the following bacterial strains twice a day, 3-month: Bifidobacterium lactis W52, Lactobacillus brevis W63, Lactobacillus casei W56, Lactococcus lactis W19, Lactococcus lactis W58, Lactobacillus acidophilus W37, Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Lactobacillus salivarius W24 |
| Measure | Description | Time Frame |
|---|---|---|
| Qualitative assessment of intestinal microbiota in stool samples | gut bacteria species in stool will be assessed using the shallow shotgun sequencing method, NGS (Next Generation Sequencing) | up to 10 months |
| Quantitive change in intestinal microbiota in stool samples | determination of quantitative (Colony forming units - CFU) changes in bacteria in the stool - the shallow shotgun sequencing method, NGS (Next Generation Sequencing) molecular analysis will be used to assess the changes | up to 10 months |
| Intestinal metabolome in stool samples | metabolomic analysis (endogenous metabolism (catabolism of amino acids, lipids), biotransformation products under the influence of xenobiotics (e.g., caffeine), fatty acid biosynthesis, fatty acid derivatives, glycolysis, gluconeogenesis, biosynthesis of primary bile acids, amino acid metabolism, sphingolipid metabolism, unknown metabolites, non-targeted metabolome, short-chain fatty acids) will be performed on a quadrupole mass spectrometer coupled with a time-of-flight (QToF) analyzer connected to the AB Sciex - TripleTOF® 6600+ high performance liquid chromatograph (UHPLC) | up to 10 months |
| Indicators of insulin sensitivity and carbohydrate metabolism | Analysis of biochemical indicators related to insulin resistance such as concentrations of glucose, insulin, insulin-like growth factor (IGF-1), hemoglobin A1C (HgA1C), myoglobin | up to 10 months |
| Evaluation of indicators in stool | Determination of intestinal inflammatory index - fecal calprotectin, determination of intestinal permeability index - fecal zonulin and determination of intestinal membrane inflammatory index sIgA in feces (RT-PCR and Western blotting). |
| Measure | Description | Time Frame |
|---|---|---|
| Gastrointestinal disorders questionnaire | assessment of gastrointestinal disorders using the Rome IV Questionnaire for adults (selected questions on irritable bowel syndrome, constipation and diarrhea); the statements of the questionnaire relate to frequency and intensity of disorders; higher scores mean worse outcome | up to 10 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joanna Karolkiewicz, Prof | Poznan University of Physical Education | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Poznan University of Physical Education | Poznan | 61-871 | Poland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41852479 | Derived | Ratajczak M, Bilska A, Musialik K, Skonieczna-Zydecka K, Loniewski I, Gogojewicz A, Karolkiewicz J. Multi-strain probiotic reduces gastrointestinal side effects in women with elevated HOMA-IR index treated with metformin: a 12-week randomised controlled trial. Front Endocrinol (Lausanne). 2026 Mar 3;17:1765741. doi: 10.3389/fendo.2026.1765741. eCollection 2026. |
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|
| the group GP (placebo) | Dietary Supplement | The placebo group will receive 2 capsules consisting of the probiotic product carrier, which is corn starch and maltodextrin, twice a day, 3-month. |
|
| up to 10 months |
| Indicators of lipid metabolism | Concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, oxidatively modified LDL lipoprotein (oxLDL), paraoxonase (PON) activity, proprotein convertase subtilisin/kexin 9 (PCSK-9) | up to 10 months |
| Transcription factors regulating carbohydrate and lipid metabolism | Peroxisome proliferator-activated receptor (PPARγ; NR1C3), PPARγ coactivator, coactivator 1 α ( PGC -1α) | up to 10 months |
| Adipokines and myokines | Analysis of biochemical indicators related to insulin resistance such as leptin, adiponectin, resistin, wisfatin, retinol-binding protein type 4 (RBP4), lipocalin-2, proprotein convertase subtilisin/kexin type 9 (PCSK9) | up to 10 months |
| Indicators of inflammation | C-reactive protein (hsCRP), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF-alpha), lipocalin-2 | up to 10 months |
| Indicators of vascular endothelial function | Analysis of biochemical indicators related to insulin resistance and endothelial function, such as endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), homocysteine, plasminogen activator inhibitor 1 (PAI-1), adhesion molecules (sVCAM-1, ICAM-1), monocyte chemoattractant 1(MCP-1), matrix metalloproteinases (MMP-9 and MMP-2), cytosolic fatty acid binding proteins (FABPs) | up to 10 months |
| Indicators of a disrupted intestinal barrier in the blood | zonulin, intestinal fatty acid binding protein (I-FABP) | up to 10 months |
| Body mass analysis (BMI, kg/m^2) |
determination of body weight and composition using the electrical bioimpedance method |
| up to 10 months |
| Body composition analysis (percent of total body mass | assessment of bone, fat and fat-free mass using the electrical bioimpedance method | up to 10 months |
| Composite measure of Diet composition assessed by food diaries | assessment of protein, fat, carbohydrates, fibre, minerals and vitamins intake using food diaries (grams) | up to 10 months |
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D019936 | Probiotics |
| ID | Term |
|---|---|
| D019587 | Dietary Supplements |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |
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