Modulation of Gut Microbiota Composition and Gut Permeability Profiles by Multispecies Synbiotic Supplementation in Hemodialysis Patients

Chronic kidney disease (CKD) patients undergoing maintenance hemodialysis experience profound alterations in their gut microbiota, leading to dysbiosis and increased gut permeability. This disruption facilitates the translocation of endotoxins and gut-derived uremic toxins such as indoxyl sulfate and p-cresyl sulfate into the systemic circulation, contributing to heightened systemic inflammation, cardiovascular disease risk, and accelerated CKD progression.

Synbiotic supplementation, particularly multispecies formulations, has emerged as a promising therapeutic strategy to restore gut microbial balance, enhance intestinal barrier integrity, and reduce the systemic burden of deleterious microbial metabolites. These probiotics potentially improve clinical outcomes by modulating inflammatory pathways and decreasing circulating levels of uremic toxins.

Despite these insights, few clinical trials have comprehensively assessed the effects of multispecies synbiotic on fecal microbiome composition, gut permeability and uremic toxin profiles in hemodialysis patients. This pilot study aims to fill this gap by evaluating the modulatory effects of a 12-week multispecies synbiotic intervention.

Study Overview

• Status: Recruiting
• Conditions: Hemodialysis; Gut -Microbiota; Gut Permeability; Uremic Toxins; Symbiotic
• Intervention / Treatment: Dietary supplement: Multispecies Synbiotic Supplementation

Detailed Description

Study Design and Objectives

This investigation is a single-arm, open-label pilot trial designed to assess the impact of a multispecies synbiotic supplementation on gut-derived uremic toxins and fecal microbiota composition over 12 weeks in adults with in a group of hemodialysis patients.

The primary objectives are to:

• Evaluate changes in fecal microbiomes,
• Assess the serum levels of uremic toxins and gut permeability markers

Study Population

• Inclusion criteria: Adults aged 18 years or older receiving maintenance hemodialysis patients for at least 3 months
• Exclusion criteria:
• Use of probiotic supplements within the last month;
• Hospitalization within the past month for acute infections or CKD-related complications;
• History of major intestinal surgeries (gastrectomy, cholecystectomy; appendectomy allowed);
• Presence of viral hepatitis, liver cirrhosis, active malignancy, advanced congestive heart failure, or thyroid disorders;
• Use of antibiotics or immunosuppressive therapy within the preceding three months.

Sample Size Justification This pilot study targets 30 participants, which provides adequate power (80%, alpha 0.05) to detect a medium effect size (Cohen's d = 0.6) on the primary outcome, serum indoxyl sulfate levels. Calculations based on expected changes from 8.0 mg/L to 6.5 mg/L with SD of 2.5 mg/L indicate a required sample size of ~24; the sample size accounts for potential dropouts to ensure study robustness.

Study Procedures

• Baseline assessments:
• Measurement of serum and urine uremic toxins,
• Measurement of gut permeability markers
• Fecal microbiome analysis
• Intervention:

Participants will receive Renobiome multispecies synbiotic containing 30 billion CFUs per capsule, including strains of Lactobacillus rhamnosus (strain ID pending), Lactobacillus salivarius LS 159, Lactobacillus pentosus LPE 588, and Lactococcus lactis LL 358 with additional prebiotics

• Dose: One capsule twice daily (morning and evening), with or without food, taken with room-temperature water.
• Storage: Capsules to be kept below 25°C, in a dry, light-protected environment.
• Follow-up and Monitoring:
• At 4 weeks: Monitoring and documentation of gastrointestinal symptoms and adverse events.
• At 12 weeks: Repeat evaluations identical to baseline, including blood and urine tests.

Compliance and Safety

• Adherence will be tracked via regular follow-up contacts.
• An adherence rate of 80-100% is considered acceptable.
• All adverse drug reactions and any unexpected events will be recorded throughout the study duration.

Biological Sample Collection and Laboratory Methods

• Blood Sampling:
• Fasting blood samples will be collected following an 8-hour fast.
• Samples will be centrifuged at 3,000 rpm for 10 minutes within 1 hour post-collection.
• Serum aliquots (200 μL) will be stored at -80°C until batch analysis.
• Intestinal permeability markers: Intestinal fatty acid-binding protein (I-FABP), diamine oxidase (DAO),and zonulin (human)
• Concentrations of indoxyl sulfate (IS), p-cresyl sulfate (PCS), indole acetic acid (IAA), and indolelactic acid (ILA) in serum and urine will be determined by high-performance liquid chromatography (HPLC) according to established protocols.
• Fecal microbiome analysis

Ethical Considerations

• Written informed consent will be obtained from all participants before enrollment.
• The study will be conducted in compliance with Taiwanese Good Clinical Practice (GCP) guidelines, local regulatory requirements, and the Declaration of Helsinki.
• Ethical approval has been granted by the Institutional Review Board of Tungs' Taichung MetroHarbour Hospital.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Paik Seong Lim, PhD; Phone Number: +886935045292; Email: jamespslim@gmail.com

Study Locations

• Taiwan
  • Wuqi District
    • Taichung, Wuqi District, Taiwan, 435
      • Recruiting
      • Tungs' Taichung Metroharbour Hospital
      • Contact: Paik Seong Lim, PhD; Phone Number: +886935045292; Email: jamespslim@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18 years or older receiving maintenance hemodialysis patients for at least 3 months

Exclusion Criteria:

1. Use of probiotic supplements within the last month;
2. Hospitalization within the past month for acute infections or CKD-related complications;
3. History of major intestinal surgeries (gastrectomy, cholecystectomy; appendectomy allowed);
4. Presence of viral hepatitis, liver cirrhosis, active malignancy, advanced congestive heart failure, or thyroid disorders;
5. Use of antibiotics or immunosuppressive therapy within the preceding three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Multispecies synbiotic; Participants will receive Renobiome multispecies synbiotic containing 30 billion CFUs per capsule, including strains of Lactobacillus rhamnosus (strain ID pending), Lactobacillus salivarius LS 159, Lactobacillus pentosus LPE 588, and Lactococcus lactis LL 358. • Dose: One capsule twice daily (morning and evening), with or without food, taken with room-temperature water. • Storage: Capsules to be kept below 25°C, in a dry, light-protected environment.

Dietary supplement: Multispecies Synbiotic Supplementation; Participants will receive Renobiome multispecies synbiotic containing 30 billion CFUs per capsule, including strains of Lactobacillus rhamnosus (strain ID pending), Lactobacillus salivarius LS 159, Lactobacillus pentosus LPE 588, and Lactococcus lactis LL 358. • Dose: One capsule twice daily (morning and evening), with or without food, taken with room-temperature water. • Storage: Capsules to be kept below 25°C, in a dry, light-protected environment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate changes in fecal microbiomes	This study employed **whole genome sequencing (WGS)** for fecal microbial analysis.Alpha diversity is estimated by species richness using the Chao1 index at the OTU level. A rarefaction curve is generated by randomly selecting a subset of sequencing data from each sample to represent the number of observed species, and a species accumulation curve is plotted to show the occurrence of new OTUs (species) with continuous sampling. For beta diversity, Bray-Curtis dissimilarities at the OTU level are calculated and analyzed using the vegan package. Differential abundance analysis was performed using statistical methods appropriate for compositional microbiome and functional gene data (such as LEfSe, ANCOM-BC, ALDEx2, MaAsLin2, or DESeq2). Multiple hypothesis testing was adjusted using the Benjamini-Hochberg false discovery rate (FDR) correction.	1 years
Assess the serum levels of uremic toxins	Concentrations of indoxyl sulfate (IS), p-cresyl sulfate (PCS), indole acetic acid (IAA), and indolelactic acid (ILA) in serum and urine will be determined by high-performance liquid chromatography (HPLC) according to established protocols.	1 years
Assess the serum levels of and gut permeability markers	Quantification of gut permeability markers, such as intestinal fatty acid-binding protein (I-FABP), diamine oxidase (DAO), and zonulin concentrations, using validated ELISA kits.	1 years

Collaborators and Investigators

• Sponsor: Tungs' Taichung Metroharbour Hospital
• Investigators: Study Chair: Paik Seong Lim, PhD, Tungs' Taichung Metroharbour Hospita

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 25, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: gut microbiome; gut permeability; uremic toxins; hemodialysis patients; multispecies synbiotic
• Other Study ID Numbers: 114109; TTMHH-R1150028 (Other Grant/Funding Number: Tungs' Taichung Metroharbor Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all collected IPD, all IPD that underlie results in a publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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