Effects of Berberine on the Human Gut Microbiome

Effects of Berberine on the Human Gut Microbiome: An Exploratory Study in Healthy Volunteers and Patients With Colorectal Adenomas

Berberine hydrochloride is a conventional component in Chinese medicine. In recent years, anticancer activity of berberine hydrochloride have been explored. The aim of this study is to investigate the effect of berberine hydrochloride on the human gut microbiome.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Adenomas; Colorectal Cancers
• Intervention / Treatment: Drug: Berberine Hydrochloride

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

Contacts and Locations

• Study Contact: Name: Ziran Kang, M.D.; Phone Number: (86)18826429521; Email: renekang@foxmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Outpatients undergoing colonoscopy at Renji Hospital who meet the following criteria:

1. Aged 18-75 years;
2. Had at least one but no more than six histologically confirmed colorectal adenomas (including tubular, tubulovillous, and villous adenomas) removed within 6 months prior to enrollment;
3. Provide informed consent for this study and are able to comply with the requirements for collecting qualified stool specimens, peripheral blood specimens, and providing relevant lifestyle and medical history information.

Healthy subjects who meet the following criteria:

1. Aged 18-75 years;
2. Have undergone colonoscopy within 6 months prior to enrollment with no histologically confirmed colorectal adenomas (including tubular, tubulovillous, and villous adenomas);
3. Provide informed consent for this study and are able to comply with the requirements for collecting qualified stool specimens, peripheral blood specimens, and providing relevant lifestyle and medical history information.

Exclusion Criteria:

The following outpatients undergoing colonoscopy at Renji Hospital:

1. Incomplete resection of adenoma during colonoscopy;
2. Individuals at high risk for hereditary colorectal cancer;
3. Regular use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, calcium, or vitamin D (defined as daily intake of ≥100 mg aspirin and ≥1200 mg calcium for at least 3 months);
4. History of subtotal gastrectomy, total gastrectomy, or partial enterectomy;
5. History of severe cardiac, hepatic, renal disease, or cancer;
6. Severe constipation or psychiatric disorders;
7. Pregnant, breastfeeding, or planning to become pregnant;
8. Undergone colonoscopy with inadequate bowel preparation (rated as "poor" or "insufficient" according to the Aronchik scale) or short observation time (withdrawal time <6 minutes).
9. Use of antibiotics, probiotics, or prebiotics within 1 month prior to enrollment.

The following healthy subjects:

1. Individuals at high risk for hereditary colorectal cancer;
2. Regular use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, calcium, or vitamin D (defined as daily intake of ≥100 mg aspirin and ≥1200 mg calcium for at least 3 months);
3. History of subtotal gastrectomy, total gastrectomy, or partial enterectomy;
4. History of severe cardiac, hepatic, renal disease, or cancer;
5. Severe constipation or psychiatric disorders;
6. Pregnant, breastfeeding, or planning to become pregnant;
7. Undergone colonoscopy with inadequate bowel preparation (rated as "poor" or "insufficient" according to the Aronchik scale) or short observation time (withdrawal time <6 minutes).
8. Use of antibiotics, probiotics, or prebiotics within 1 month prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Berberine hydrochloride administration	Drug: Berberine Hydrochloride; Oral Administration of Berberine Hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative abundance of Akkermansia in fecal samples as measured by quantitative PCR (qPCR)	Fecal samples will be collected at baseline (prior to berberine hydrochloride administration) and after treatment. The relative abundance of Akkermansia will be quantified using quantitative PCR (qPCR) targeting species-specific 16S rRNA gene sequences. Results will be expressed as the relative abundance normalized to total bacterial load (ΔCt method). Changes from baseline to post-treatment will be calculated for each participant and summarized across the study population.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative abundance and diversity of gut microbiota in fecal samples as assessed by 16S rRNA gene sequencing	Fecal samples will be collected at baseline (prior to berberine hydrochloride administration) and after treatment. Gut microbiota composition will be analyzed using 16S rRNA gene sequencing. Outcomes will include: relative abundance of bacterial taxa at the phylum and genus levels (excluding Akkermansia where applicable), and; alpha diversity indices (Shannon index). Changes from baseline to post-treatment will be calculated for each participant and summarized across the study population.	2 weeks
Plasma concentration of indole-3-pyruvic acid (IPyA) as measured before and after berberine hydrochloride administration	Peripheral blood samples will be collected at baseline (prior to berberine hydrochloride administration) and after treatment. The concentration of indole-3-pyruvic acid (IPyA) in plasma will be quantified using a validated analytical method (liquid chromatography-mass spectrometry, LC-MS). Changes in IPyA concentration from baseline to post-administration will be calculated for each participant and summarized across the study population.	2 weeks
Fecal concentration of indole-3-pyruvic acid (IPyA) as measured before and after berberine hydrochloride administration	Fecal samples will be collected at baseline (prior to berberine hydrochloride administration) and after treatment. The concentration of indole-3-pyruvic acid (IPyA) in fecal samples will be quantified using a validated analytical method (liquid chromatography-mass spectrometry, LC-MS). Changes in IPyA concentration from baseline to post-administration will be calculated for each participant and summarized across the study population.	2 weeks
Number of participants with abnormal liver and renal function laboratory values	Blood samples will be collected at baseline (prior to berberine hydrochloride administration) and after treatment. Liver function will be assessed by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and albumin. Renal function will be evaluated using serum creatinine (Cr) and blood urea nitrogen (BUN). Abnormal laboratory values will be defined according to institutional reference ranges. The number and proportion of participants with abnormal values after treatment will be reported. Changes from baseline for each parameter will also be summarized descriptively.	2 weeks
Proportion of VEGFA-positive cells in adenoma tissue as assessed by immunohistochemistry	Adenoma tissue samples will be obtained at the time of endoscopic resection for patients with colorectal adenomas, before and after administration of hydrochloride berberine. Immunohistochemical staining will be performed to detect vascular endothelial growth factor A (VEGFA) expression. The proportion of VEGFA-positive cells will be quantified by calculating the percentage of positively stained cells among total cells in representative high-power fields. Results will be summarized descriptively across participants. If applicable, comparisons with baseline or between subgroups may be explored.	Baseline and at follow-up colonoscopy (approximately 6 months [±2 months] after treatment)

Collaborators and Investigators

• Sponsor: Jing-yuan Fang, MD, Ph. D
• Collaborators: Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Jingyuan Fang, M.D., Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): October 15, 2026

Study Registration Dates

• First Submitted: March 22, 2026
• First Submitted That Met QC Criteria: April 6, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: colorectal cancers; colorectal adenomas; human gut microbiome; Berberine hydrochloride
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: KY2025-112-B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No