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NCT Number: NCT07519681

Effects of Berberine on the Human Gut Microbiome

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.

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Key information

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

  • Aged 18-75 years;
  • 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;
  • 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:

  • Aged 18-75 years;
  • Have undergone colonoscopy within 6 months prior to enrollment with no histologically confirmed colorectal adenomas (including tubular, tubulovillous, and villous adenomas);
  • 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:

  • Incomplete resection of adenoma during colonoscopy;
  • Individuals at high risk for hereditary colorectal cancer;
  • 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);
  • History of subtotal gastrectomy, total gastrectomy, or partial enterectomy;
  • History of severe cardiac, hepatic, renal disease, or cancer;
  • Severe constipation or psychiatric disorders;
  • Pregnant, breastfeeding, or planning to become pregnant;
  • Undergone colonoscopy with inadequate bowel preparation (rated as "poor" or "insufficient" according to the Aronchik scale) or short observation time (withdrawal time <6 minutes).
  • Use of antibiotics, probiotics, or prebiotics within 1 month prior to enrollment.

The following healthy subjects:

  • Individuals at high risk for hereditary colorectal cancer;
  • 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);
  • History of subtotal gastrectomy, total gastrectomy, or partial enterectomy;
  • History of severe cardiac, hepatic, renal disease, or cancer;
  • Severe constipation or psychiatric disorders;
  • Pregnant, breastfeeding, or planning to become pregnant;
  • Undergone colonoscopy with inadequate bowel preparation (rated as "poor" or "insufficient" according to the Aronchik scale) or short observation time (withdrawal time <6 minutes).
  • Use of antibiotics, probiotics, or prebiotics within 1 month prior to enrollment.

Treatment and study plan

Berberine Hydrochloride

Drug

Oral Administration of Berberine Hydrochloride

Primary outcomes

  1. Relative abundance of Akkermansia in fecal samples as measured by quantitative PCR (qPCR)

    Time frame: 2 weeks

    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.

Secondary outcomes

  1. Relative abundance and diversity of gut microbiota in fecal samples as assessed by 16S rRNA gene sequencing

    Time frame: 2 weeks

    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. Plasma concentration of indole-3-pyruvic acid (IPyA) as measured before and after berberine hydrochloride administration

    Time frame: 2 weeks

    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.

  3. Fecal concentration of indole-3-pyruvic acid (IPyA) as measured before and after berberine hydrochloride administration

    Time frame: 2 weeks

    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.

  4. Number of participants with abnormal liver and renal function laboratory values

    Time frame: 2 weeks

    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.

  5. Proportion of VEGFA-positive cells in adenoma tissue as assessed by immunohistochemistry

    Time frame: Baseline and at follow-up colonoscopy (approximately 6 months [±2 months] after treatment)

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Ziran Kang, M.D.

CONTACT

[email protected]

(86)18826429521

Sponsors and collaborators

Lead sponsor

Jing-yuan Fang, MD, Ph. D

Other

Collaborators

  • Shanghai Jiao Tong University School of Medicine

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2026
Study completion
2026
First posted
Apr 9, 2026
Registry last updated
May 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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