Research on Gut Microbiota and Metabolomics in Diabetic Kidney Disease

Research on Gut-kidney Axis Regulation of Diabetic Kidney Disease Based on Multi-omics and Bacterio-drug Interaction Control Mechanism

Diabetic kidney disease (DKD) is characterized by high prevalence, multiple pathogenesis, and lack of effective treatment and management strategies. Early detection helps overcome treatment inertia, enables timely medical intervention, maximizes renal function in diabetic patients, and is essential to avoid renal failure and improve clinical outcomes. The gold standard for diagnosis of DKD is renal biopsy, which has the highest accuracy. However, due to the trauma of renal biopsy, the patient acceptance is low, the application scenario is not universal, and it is only used when it is difficult to distinguish diabetic nephropathy from non-diabetic nephropathy, and it is not the preferred diagnostic method for DKD.

In the past decade, with the emergence and application of metabonomics, proteomics, genomics and other multi-omics techniques, more and more studies have recognized the prominent role of intestinal flora disorders and gut-derived metabolites in the occurrence of DKD. Therefore, from the perspective of intestinal flora, using multi-omics techniques to identify enterogenic metabolic markers of DKD and restore intestinal flora balance may be potential strategies for prevention and management of DKD. Modern medicine believes that intestinal flora is not only closely related to diet and digestion, participating in the synthesis, absorption and metabolism of nutrients, but also constituting intestinal barrier and participating in immune defense of the body. Its function is similar to the physiological function of "The spleen governs transportation and transformation".

Based on the traditional Chinese medicine（TCM） pathogenesis of DKD "Spleen Failure to Disperse Essence and Poison Damage Kidney Collateral" proposed by the previous research group, this study intends to use microbiology-metabolomics to deeply study the TCM pathogenesis of DKD, provide scientific basis for it, and guide the theory of traditional Chinese medicine widely used in clinical work of prevention and treatment of diabetic nephropathy.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Disease; Type 2 Diabetes Mellitus (T2DM); Diabetic Nephropathy Type 2

Detailed Description

This study is a single-center, parallel trial design. It is prepared to recruit subjects with type 2 diabetes kidney disease (DKD), Type 2 diabetes mellitus(T2DM), chronic kidney disease (CKD), and healthy individuals based on clinical diagnostic criteria and screening criteria. While observing main indicators such as blood glucose, glycosylated hemoglobin, and renal function, blood, urine, feces, and tongue coating samples are collected and frozen. The 16S rDNA technology, metagenomics technology, targeted and non-targeted metabolomics technology are used to detect the results and analyze the differences. Subsequently, based on the detection results, 4-6 remaining fecal samples from each group will be selected as human-intestinal flora donors for "human-germ-free mouse" faecal microbiota transplantation.

• Study Type: Observational
• Enrollment (Estimated): 720

Contacts and Locations

• Study Contact: Name: Xiang ning Huang, Doctor; Phone Number: 86-18229942526; Email: yirenxinlu@foxmail.com
• Study Contact Backup: Name: Na Tian, Doctor; Phone Number: 86-18374807942; Email: 819062608@qq.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410007
      • Recruiting
      • The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine
      • Contact: Xiang ning Huang, Doctor; Phone Number: 86-18229942526; Email: yirenxinlu@foxmail.com
      • Contact: Na Tian, Doctor; Phone Number: 86-18374807942; Email: 819062608@qq.com
      • Principal Investigator: Tian Na Doctor Tian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients are treated at the Department of Endocrinology or the Department of Nephrology in the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, and those who meet the inclusion criteria. At the same time, healthy people who meet the inclusion criteria are recruited through recruitment advertisements.

Description

Patient inclusion criteria：

1. Age ≥18 years old and ≤75 years old, gender is not limited.
2. Complete demographic data.
3. Meet the diagnostic criteria of the Chinese Guidelines for the Prevention and Treatment of Diabetic Kidney Disease (2021 edition), the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes Mellitus (2020 edition), and the Guidelines for the Screening, Diagnosis, Prevention and Treatment of Chronic Kidney Disease (2017 edition).
4. The patient is informed of the study as approved by the ethics committee.

Healthy population inclusion criteria:

(1) The patient has no known history of infection or risk factors including HIV hepatitis B or C virus syphilis etc. and no current systemic infection; (2) No obesity (body mass index >30) and/or diabetes no history of chronic kidney disease; (3) Approved by the ethics committee patients were informed about the study. Exclusion criteria：

1. A history of infection or other acute disease within one month prior to enrollment.
2. Current state of stress.
3. Other unstable chronic diseases;
4. A history of acute and chronic gastrointestinal diseases, including acute gastroenteritis, functional gastrointestinal diseases, inflammatory bowel disease, celiac disease, and other chronic gastrointestinal diseases.
5. Individuals who have received systemic antibiotics, immunosuppressants, chemotherapy, or chronic treatment with proton pump inhibitors within the past three months will be excluded from participation.
6. Pregnant or lactating women will also be excluded.
7. Individuals who have participated in other drug clinical trials within the past three months will be excluded.
8. Individuals who suffer from mental illness, intellectual disability, confusion, or other conditions that may interfere with their ability to cooperate with the completion of relevant information collection will also be excluded.

Those who were unable to cooperate with the collection of pertinent data were likewise excluded from the study.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Type 2 Diabetes Kidney Disease; Clinical diagnostic criteria consistent with Type 2 Diabetes Kidney Disease
Type 2 Diabetes Mellitus; Clinical diagnostic criteria consistent with Type 2 Diabetes Mellitus(T2DM)
Chronic Kidney Disease; Clinical diagnostic criteria consistent with Chronic Kidney Disease (CKD)
healthy people; Relatively healthy people without diabetes and chronic kidney disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UACR	Urine Albumin-to-Creatinine Ratio	Complete once at enrollment
eGFR	Estimated Glomerular Filtration Rate	Complete once at enrollment
BUN	blood urea nitrogen	Complete once at enrollment
Scr	serum creatinine	Complete once at enrollment
FBG	fasting blood glucose	Complete once at enrollment
HbA1c	Glycosylated Hemoglobin, Type A1C	Complete once at enrollment
GSP	glucosylated serum protein	Complete once at enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
16S rDNA	16S ribosomal DNA identification	Complete once at enrollment
Targeted Metabolomics	Targeted Metabolomics technology detection	Complete once at enrollment
Non-targeted metabolomics	Non-targeted metabolomics technology detection	Complete once at enrollment
mNGS	metagenomic Next Generation Sequencing	Complete once at enrollment

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine
• Collaborators: National Natural Science Foundation of China
• Investigators: Principal Investigator: Juan Huang, Doctor, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine; Study Director: Rong Yu, Doctor, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2022
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: February 13, 2025
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: chronic kidney disease; Type 2 diabetes mellitus; metabolomics; intestinal microbiota; Diabetic Nephropathy Type 2
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Complications; Renal Insufficiency; Diabetes Mellitus, Type 2; Diabetes Mellitus; Kidney Diseases; Renal Insufficiency, Chronic; Diabetic Nephropathies
• Other Study ID Numbers: U21A20411

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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