Impact of Intestinal Microbiota on Uremic Toxins Productions

NCT04768309 | Completed

• 1 other identifier: 69HCL20_1078
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CKD; Uremia

Keywords

CKD; uremic toxin; probiotics; intestinal microbiota; artificial intestine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Uremic toxins production

  48 hours after instillation of fresh feces in the human intestine simulator

• Production of short-chain fatty acids (SCFA)

  48 hours after instillation of fresh feces in the human intestine simulator

• Intestinal permeability in a human intestine simulator

  48 hours after instillation of fresh feces in the human intestine simulator

• Biochemical parameters

  48 hours after instillation of fresh feces in the human intestine simulator

• Biochemical parameters

  48 hours after instillation of fresh feces in the human intestine simulator

Study Arms (2)

CKD group

EXPERIMENTAL

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

Healthy volunteers group

OTHER

Adult without chronic treatment, without renal dysfunction

Other: Ex vivo exploration of the effect of a probiotic over precursor indole production

Interventions

Ex vivo exploration of the effect of a probiotic over precursor indole production OTHER

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.

CKD group; Healthy volunteers group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Lyon Sud University Hospital

Pierre-Bénite, Rhône, 69310, France

Location

Related Publications (1)

• Beau A, Natividad J, Benoit B, Delerive P, Duboux S, Feng Y, Jammes M, Barnel C, Sequino G, Pinteur C, Glorieux G, Fouque D, Vidal H, Koppe L. A specifically designed multi-biotic reduces uremic toxin generation and improves kidney function. Gut Microbes. 2025 Dec;17(1):2531202. doi: 10.1080/19490976.2025.2531202. Epub 2025 Jul 12.

  PMID: 40650408 RESULT

MeSH Terms

Conditions

Uremia

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: February 24, 2021
• Study Start: June 4, 2021
• Primary Completion: July 13, 2021
• Study Completion: July 13, 2021
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

FR (1)