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

NCT07313007 · Status: NOT_YET_RECRUITING · Phase: NA · Type: INTERVENTIONAL · Enrollment: 24

Last updated 2026-04-03

No results posted yet for this study

Summary

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

Conditions

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

Interventions

PROCEDURE

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

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.

Sponsors & Collaborators

  • Hospices Civils de Lyon

    lead OTHER

Study Design

Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2026-05-01
Primary Completion
2026-11-01
Completion
2026-11-01

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07313007 on ClinicalTrials.gov