Eradication of Helicobacter Pylori Improves Metabolic Syndrome Through Modulation of Gut Microbiota.

Mechanisms of Gut Microbiota in Improving Metabolic Syndrome-Related Parameters Following Helicobacter Pylori Eradication

The Role of Gut Microbiota in the Mechanism of Helicobacter pylori Eradication-Induced Amelioration of Metabolic Syndrome-Related Parameters

Study Sponsor: Nanjing First Hospital Principal Investigator: Dr. Wanli Liu Department: Gastroenterology Study Duration: February 2025 - August 2025

Key Information for Patients and Families

1. What is this study about? This study aims to understand how treating a common stomach infection caused by Helicobacter pylori (Hp) might improve metabolic health issues like high blood sugar, cholesterol problems, or obesity (collectively called metabolic syndrome). Specifically, it explores whether adding probiotics (good bacteria) or a natural compound called berberine (BBR) to standard Hp treatment can enhance these benefits by improving gut bacteria balance.

2. Who can participate? Patients: Adults aged 18-65 with both Helicobacter pylori infection (confirmed by a breath test) and newly diagnosed metabolic syndrome (based on waist size, blood sugar, cholesterol, or blood pressure).

   Healthy Volunteers: Adults aged 18-65 with no Hp infection and normal metabolic health (to compare results).

   Exclusions:

   Allergy to study medications (e.g., penicillin).

   Previous Hp treatment, recent antibiotic/steroid use, pregnancy, or serious medical conditions (e.g., liver/kidney disease).

3. What will participants do?

   Treatment Groups:

   Group A: Take two medications (vonoprazan + amoxicillin) for 14 days.

   Group B: Take the two medications + probiotics (Bifidobacterium tablets).

   Group C: Take the two medications + berberine (a plant-based supplement).

   Tests:

   Before treatment: Breath test, blood tests (blood sugar, cholesterol, inflammation markers), stool sample analysis (gut bacteria), and body measurements (weight, waist size).

   After treatment (1 month): Repeat tests to check Hp eradication and metabolic improvements.

4. Possible Benefits and Risks

   Benefits:

   Free Hp treatment and metabolic health monitoring.

   Potential improvement in blood sugar, cholesterol, or weight.

   Contribution to future treatments for metabolic syndrome.

   Risks:

   Mild side effects (e.g., nausea, diarrhea, stomach pain) from medications.

   Discomfort from blood draws or stool sample collection.

5. How are participants protected? All treatments are FDA-approved or widely used in clinical practice.

Ethical review ensures participant safety.

You can withdraw at any time without affecting your regular care.

Information for Health Care Providers

1. Study Design Type: Prospective, single-center, open-label, randomized controlled trial.

   Population: 140 participants (120 Hp+ patients with metabolic syndrome; 20 Hp- healthy controls).

   Intervention:

   Group A: Vonoprazan (20 mg bid) + amoxicillin (1 g tid) for 14 days.

   Group B: Group A + Bifidobacterium tetragenous probiotic (3 tablets tid).

   Group C: Group A + berberine (3 tablets tid).

   Primary Outcomes:

   Hp eradication rate (confirmed by urea breath test).

   Changes in metabolic parameters (fasting glucose, HbA1c, lipid profile).

   Gut microbiota composition (16S rRNA sequencing).

   Secondary Outcomes:

   Multi-omics analysis (inflammation markers, endotoxins, short-chain fatty acids, bile acids).

2. Scientific Rationale Hp and Metabolic Syndrome: Epidemiological evidence links Hp infection to metabolic dysfunction, possibly via chronic inflammation. Eradication may partially reverse insulin resistance and dyslipidemia.

   Gut Microbiota as Mediator: Hp eradication alters gut microbiota, which regulates metabolic homeostasis through metabolites (e.g., SCFAs), bile acid metabolism, and inflammatory pathways. Probiotics/BBR may enhance these effects.

3. Methodology Randomization: Block randomization (block size = 4) using SAS 9.4.

   Assessments:

   Metabolic Parameters: Fasting glucose, HbA1c, lipid profile, BMI.

   Microbiome: 16S rRNA sequencing (α/β diversity, taxa abundance).

   Multi-omics: ELISA (TNF-α, IL-6), GC-MS (SCFAs), UPLC-MS (bile acids).

   Statistical Analysis:

   Microbiome: QIIME2, LEfSe, PICRUSt2.

   Multi-omics: limma, SparCC, sPLS-DA.

   Clinical data: ANOVA, χ² tests (SPSS v25.0).

4. Clinical Implications Clarify whether probiotics or BBR add value to Hp eradication in improving metabolic health.

Identify gut microbiota-driven mechanisms linking Hp eradication to metabolic benefits.

Resources for Participants

Study Flowchart:

Screening: Breath test, blood/stool tests (1 week).

Treatment: 14 days of medication.

Follow-up: Repeat tests at 1 month.

Contact Information:

Dr. Wanli Liu: +86-18951670222

Nanjing First Hospital Gastroenterology Department.

FAQ Sheet:

Can I take my regular medications? Yes, unless they interfere with Hp treatment (e.g., PPIs).

What if I miss a dose? Contact the study team immediately.

Ethical Compliance Approved by the Institutional Review Board of Nanjing First Hospital.

Complies with the Declaration of Helsinki and China's ethical guidelines.

Informed consent required for participation.

Study Overview

• Status: Recruiting
• Conditions: Metabolic Syndrome; HELICOBACTER PYLORI INFECTIONS
• Intervention / Treatment: Drug: Vonoprazan-Amoxicillin Dual Therapy; Drug: Vonoprazan-Amoxicillin with Bifidobacterium tetravaccae; Drug: Vonoprazan-Amoxicillin with Berberine

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Wanli Liu; Phone Number: +86 18951768998; Email: 18951768998@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Recruiting
      • Nanjing First Hospital, Nanjing Medical University
      • Contact: Ruolin Peng; Phone Number: +86 15913195399; Email: 3480502961@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• For H. pylori-naïve infected patients with newly diagnosed metabolic syndrome (MS):

  1. Aged 18-65 years;
  2. Confirmed H. pylori-positive status by urea breath test (UBT), with no prior eradication therapy;
  3. Newly diagnosed MS according to the Chinese Diabetes Society (CDS, 2004 Chinese criteria) ;
  4. Voluntarily join the trial and sign informed consent.

• For H. pylori-negative healthy controls with normal metabolism:

  1. Aged 18-65 years;
  2. Confirmed H. pylori-negative status by UBT;
  3. Normal metabolic parameters (e.g., blood glucose, lipid profile, blood pressure) without MS;
  4. Voluntarily join the trial and sign informed consent.

Exclusion Criteria:

1. Hypersensitivity to study drugs (e.g., penicillin, amoxicillin, vonoprazan);
2. Active peptic ulcer confirmed by endoscopy;
3. Prior history of H. pylori eradication therapy;
4. Use of medications for metabolic regulation (e.g., hypoglycemic agents, lipid-lowering drugs, weight-loss drugs)
5. Recent use of antibiotics or bismuth (within 4 weeks) or H2-receptor antagonists/PPIs (within 2 weeks) before enrollment;
6. Current use of corticosteroids, NSAIDs, or anticoagulants;
7. History of esophageal or gastric surgery;
8. Pregnant or breastfeeding women;
9. Severe comorbidities (e.g., hepatic, cardiovascular, pulmonary, renal diseases, inflammatory bowel disease);
10. Chronic alcohol abuse (>40 g/day for men, >20 g/day for women);
11. Malignancies (e.g., gastric mucosa-associated lymphoid tissue [MALT] lymphoma).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotics Group	Drug: Vonoprazan-Amoxicillin with Bifidobacterium tetravaccae; Patients receive oral vonoprazan 20 mg twice daily, amoxicillin 1000 mg three times daily, and Bifidobacterium tetravaccae probiotic tablets (3 tablets three times daily) for 14 days.
Experimental: VA group	Drug: Vonoprazan-Amoxicillin Dual Therapy; Patients receive oral vonoprazan 20 mg twice daily and amoxicillin 1000 mg three times daily for 14 days. This regimen is a standard dual therapy for Helicobacter pylori eradication.
Experimental: BBR Group	Drug: Vonoprazan-Amoxicillin with Berberine; Patients receive oral vonoprazan 20 mg twice daily, amoxicillin 1000 mg three times daily, and berberine hydrochloride tablets (3 tablets three times daily) for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Helicobacter pylori Eradication Rate	Post-treatment follow-up at 1 month
Change in Serum Triglycerides	Baseline and 1 month post-treatment.
Change in HDL Cholesterol	Baseline and 1 month post-treatment.
Change in Blood Pressure	Baseline and 1 month post-treatment.
Change in Waist Circumference	Baseline and 1 month post-treatment.
Change in Fasting Plasma Glucose	Baseline and 1 month post-treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in gut microbiota alpha-diversity, assessed by 16S rRNA gene sequencing		Baseline and 1 month post-treatment.
Change in gut microbiota beta-diversity, assessed by 16S rRNA gene sequencing		Baseline and 1 month post-treatment.
Identification of differentially abundant bacterial taxa (Genus level), assessed by 16S rRNA gene sequencing and statistical modeling (e.g., LEfSe or DESeq2)		Baseline and 1 month post-treatment.
Serum Levels of Inflammatory Cytokines (Including TNF-α, CRP, IL-6, and IL-8)	measured by enzyme-linked immunosorbent assay (ELISA) in serum.	Baseline and 1 month post-treatment.
Endotoxins	measured by limulus amebocyte lysate (LAL) assay in serum	Baseline and 1 month post-treatment.
Gut microbiota-derived metabolites	measured by liquid chromatography-mass spectrometry (LC-MS)	Baseline and 1 month post-treatment.

Collaborators and Investigators

• Sponsor: Nanjing First Hospital, Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: August 29, 2025
• First Submitted That Met QC Criteria: December 14, 2025
• First Posted (Actual): December 29, 2025

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Nutritional and Metabolic Diseases; Metabolic Syndrome; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Heterocyclic Compounds, 4 or More Rings; Benzylisoquinolines; Berberine Alkaloids; Berberine
• Other Study ID Numbers: KY20250327-12

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