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NCT Number: NCT07313007

Assessment of Gut Microbiota-Derived Amino Acid Metabolite Production in Patients With MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver disorders ranging from simple steatosis-a relatively benign and non-progressive condition-to metabolic dysfunction-associated steatohepatitis (MASH), characterized by hepatocellular inflammation. MASLD is now the leading cause of chronic liver disease worldwide, affecting approximately one in three adults, particularly those with obesity or type 2 diabetes.

Recent studies have highlighted a strong interconnection between the gut microbiota, the liver, metabolism, and the immune system, collectively referred to as the gut-liver axis. Alterations in the gut microbiota are observed at all stages of MASLD, and several microbial metabolites-such as trimethylamine, bile acids, short-chain fatty acids, and ethanol-have been implicated in disease progression.

Emerging evidence points to a role for gut-derived metabolites of tryptophan (Trp) and phenylalanine (Phe), including phenylacetic acid (PAA), 3-(4-hydroxyphenyl)-lactate (HPL), and phenyllactate (PL). These compounds have been associated with the severity of MASLD, particularly with hepatic steatosis and fibrosis. Elevated plasma levels of aromatic amino acids (AAAs), such as L-phenylalanine and L-tyrosine, are also correlated with increased hepatic fat content.

A newly identified Phe-derived metabolite, N-acetyl-phenylalanine (NAPA), together with PAA, HPL, and PL, has been shown to correlate with hepatic steatosis. These metabolites can induce steatosis both in vitro and in vivo, acting through the disruption of endoplasmic reticulum-mitochondria interactions. They therefore represent potential new therapeutic targets.

These four metabolites of interest (NAPA, PAA, HPL, PL) can be produced both by gut bacteria and through endogenous human metabolism. Positive correlations between plasma NAPA concentrations and specific bacterial species have been observed, although the responsible taxa remain to be identified.

HYPOTHESIS

We hypothesize that the gut microbiota of MASLD patients produces aromatic amino acid-derived metabolites, contributing to the elevated plasma concentrations observed in these patients

Two complementary strategies will be used : Human Microbiota Culture and Fecal Microbiota Transplantation

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Key information

Conditions

MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Centre Hospitalier Lyon Sud Service Endocrinologie, Diabète et nutrition

Pierre-Bénite, 69495, France

Location status: Recruiting

Location contact

Cyrielle CAUSSY, MD, PhD

CONTACT

[email protected]

+33 4 78 86 44 48

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • For patients and healthy volunteers:
  • Age between 18 and 80 years.
  • Non-diabetic participant (fasting blood glucose < 1.26 g/L, or absence of insulin therapy or oral antidiabetic medication).
  • Body mass index (BMI) between 18 and 30 kg/m².
  • For women of childbearing potential, use of at least one recognized effective contraceptive method.
  • Very regular bowel movements every 24 to 48 hours.
  • Participant living within 100 km of the Lyon Sud Hospital Center (CHLS).
  • Participant willing to participate in the study and providing written informed consent.
  • Participant affiliated with the general French Social Security system or an equivalent scheme.
  • For patients:
  • Presence of MASLD according to the definition of the European Association for the Study of the Liver (EASL), defined by hepatic steatosis on imaging performed within the previous year (abdominal ultrasound, abdominal CT scan, magnetic resonance imaging, or controlled attenuation parameter (CAP) measured by FibroScan) and at least one cardiometabolic criterion among: dyslipidemia, arterial hypertension, overweight (BMI ≥ 25 kg/m²), impaired glucose tolerance, or type 2 diabetes.
  • No history of liver transplantation.
  • No excessive alcohol consumption (less than 20 g/day for women and less than 30 g/day for men).
  • Patient followed in the Endocrinology, Diabetes and Nutrition Department at Lyon Sud Hospital.

Exclusion criteria

  • For patients and healthy volunteers:
  • Participant with active inflammatory, infectious, cardiovascular, or neoplastic disease.
  • Participant with a history of colectomy, small bowel resection, or cholecystectomy.
  • Participant who received antibiotics, prebiotics, or probiotics within the past 3 months.
  • Participant using laxatives (more than 2 doses per day over the past 3 months).
  • Participant with chronic constipation.
  • Pregnant, parturient, or breastfeeding women.
  • Participant deprived of liberty by judicial or administrative decision.
  • Participant receiving psychiatric care.
  • Participant institutionalized for reasons other than research.
  • Adult participant under legal protection (guardianship or trusteeship).
  • Participant who does not understand the French language and cannot provide informed consent.
  • Participant already enrolled in a study presenting a conflict of interest with the present study.
  • For healthy volunteers
  • Known liver disease
  • No long-term drug medication except oral contraception for women.

Treatment and study plan

stool sampling, dietary assessment, and collection of blood and urine samples

Procedure

MASLD group includes individuals receiving routine clinical care for liver-related conditions. During their scheduled medical visits, participants undergo standard clinical assessments and routine blood tests. Additional research-specific procedures-such as stool sampling, dietary assessment, and collection of blood and urine samples-are carried out without altering routine patient management. A fraction of blood sample is used for NAPA measurement. Stool samples are collected at home and returned directly to the Endocrinology, Diabetes and Nutrition Department within 24 hours after collection.

Healthy volunteers undergo the same research-specific procedures as patients but exclusively for research purposes, with no routine-care-related assessments.

Primary outcomes

  1. Concentration of NAPA in Stool Culture Medium

    Time frame: Within 30 days after Visit 1 (sample collection and analysis performed at a single time point)

    Quantification of the metabolite N-acetyl-phenylalanine (NAPA) in the culture medium of stool samples cultivated using the MiPro in vitro human gut microbiota culture system.

Secondary outcomes

  1. Concentration of Selected AAA-Derived Metabolites in Stool Culture Medium

    Time frame: Within 30 days after Visit 1 (sample collection and analysis performed at a single time point)

    Quantification of selected aromatic amino acid (AAA)-derived metabolites in the culture medium of stool samples cultivated using the MiPro in vitro human gut microbiota culture system.

  2. Gut Microbiota Composition in Stool Samples

    Time frame: Within 30 days after Visit 1 (sample collection and analysis performed at a single time point)

    Characterization of gut microbiota composition in stool samples who produce NAPA or other metabolites of interest, to identify bacterial species potentially involved in metabolite production. Microbiota profiling will be performed on a stool sample using bacterial DNA sequencing methods (16S rRNA gene sequencing or shotgun metagenomics).

  3. Concentration of NAPA in plasma

    Time frame: Baseline Visit 1 (sample collection and analysis performed at a single time point)

    The quantification of NAPA level will be performed on plasma samples

Study contacts

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

Cyrielle CAUSSY, MD, PhD

CONTACT

[email protected]

+33 4 78 86 44 48

Dominique DELAUNAY, PhD

CONTACT

[email protected]

+33 4 72 11 00 64

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Official study title

Evaluation of the Production of Amino Acid-Derived Metabolites by the Gut Microbiota of Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Acronym: MASLD-GUT

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Dec 31, 2025
Registry last updated
Jun 22, 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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