Impact of Intestinal Microbiota on Uremic Toxins Productions (GUTCOL)

Assessment of the Production of Uremic Toxins by the Gut Microbiota of Patients With Chronic Kidney Disease: in Vitro Test

Chronic renal failure (CKD) affects 3 million people in France and is characterized by the accumulation of uremic toxins (UTs) such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS) which participate in cardiovascular complications and disturbance of the carbohydrate metabolism associated with CKD. These UTs are not eliminated by dialysis due to their high affinity for albumin and alternative strategies to dialysis must be developed to decrease the production of TUs in patients not yet in dialysis. The dysregulation of the intestinal microbiota observed during CKD increases the generation of UTs in the intestine, by the transformation of amino acids derived from proteins (such as tyrosine and tryptophan transformed respectively into PCS and, IS). Thus, modulation of the intestinal microbiota seems to be an attractive target for reducing the production of UTs and the comorbidities associated with CKD. Some studies have demonstrated the potential interest of probiotics in lowering the plasma concentration of UTs, but the effects remain unclear. In order to test the interest of probiotics during CKD, the investigators have, in collaboration with the Nestlé laboratory and the ProDigest platform, the possibility of testing probiotics using a human intestine simulator before the investigation of experimental and human models. For this the investigators would need a collection of fresh stools. The fresh stools will be instilled in artificial intestine to test the efficacy of selected probiotics on UTs production.

Fresh feces in chronic kidney patients and healthy volunteers will be collected. The feces will be instilled in artificial intestine with and without selected probiotics and production of uremic toxins will be measured.

The main endpoint is the concentration of the precursor of indoxyl sulfate (indole) in the lumen of the artificial intestine with a microbiota of a patient with CKD compared to the concentration of indol in the lumen of artificial intestine with a microbiota from a patient with CKD and supplemented with a probiotic (supplied by Nestlé)

Indoles production will be measured 48 hours after instillation of fresh feces in the artificial intestine

Concentration of various uremic toxins in a human intestine simulator (p-cresyl sulfate, p-cresol, indole-3-acetic acid, etc.).

Concentration of short-chain fatty acids (SCFA) (acetate, propionate, butyrate, isobutyrate, isovalerate and isocaproate) human intestine simulator

Inclusion Criteria: Age between 18 and 80 years old Non diabetic (fasting blood glucose <1.26 g / L, or lack of insulin or oral antidiabetic treatment) BMI between 18 and 30 kg / m² Patient with CKD stage 4-5 ( eDFG < 30 ml/min/1.73m2 CKD-EPI) Not dialyzed No history of kidney transplant Patient followed in the nephrology department of Pr FOUQUE at the Lyon Sud hospital center Exclusion Criteria: Active inflammatory, infectious, cardiovascular or neoplastic disease Colectomy, resection of the small intestine or cholecystectomy Patient having received antibiotics, prebiotics, probiotics in the last 3 months. Patient using laxatives (more than 2 doses per day for the last 3 months) Known renal pathology or known urologic malformation (healthy volunteer only)