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.

Study Overview

• Status: Completed
• Conditions: CKD; Uremia
• Intervention / Treatment: Other: Ex vivo exploration of the effect of a probiotic over precursor indole production

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Rhône
    • Pierre-Bénite, Rhône, France, 69310
      • Lyon Sud University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CKD group; CKD adult patients stage 4-5 Without diabetes BMI between 18 and 30 kg/m2	Other: Ex vivo exploration of the effect of a probiotic over precursor indole 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.
Other: Healthy volunteers group; Adult without chronic treatment, without renal dysfunction	Other: Ex vivo exploration of the effect of a probiotic over precursor indole 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Production of precursor of one of major uremic toxins: indole	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uremic toxins production	Concentration of various uremic toxins in a human intestine simulator (p-cresyl sulfate, p-cresol, indole-3-acetic acid, etc.).	48 hours after instillation of fresh feces in the human intestine simulator
Production of short-chain fatty acids (SCFA)	Concentration of short-chain fatty acids (SCFA) (acetate, propionate, butyrate, isobutyrate, isovalerate and isocaproate) human intestine simulator	48 hours after instillation of fresh feces in the human intestine simulator
Intestinal permeability in a human intestine simulator	It will be measured by the electrical transepithelial resistance of the intestinal cells.	48 hours after instillation of fresh feces in the human intestine simulator
Biochemical parameters	Concentration of ammonium and lactate in a human intestine simulator.	48 hours after instillation of fresh feces in the human intestine simulator
Biochemical parameters	pH levels of the human intestine simulator.	48 hours after instillation of fresh feces in the human intestine simulator
Biochemical parameters	Volume of gas production in a human intestine simulator.	48 hours after instillation of fresh feces in the human intestine simulator
Intestinal microbiota composition	Study of the composition of the intestinal microbiota by 16s analysis	48 hours after instillation of fresh feces in the human intestine simulator

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2021
• Primary Completion (Actual): July 13, 2021
• Study Completion (Actual): July 13, 2021

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: probiotics; CKD; uremic toxin; intestinal microbiota; artificial intestine
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Uremia
• Other Study ID Numbers: 69HCL20_1078

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No