Evaluation of the Production of Amino Acid-Derived Metabolites by the Gut Microbiota of Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
概览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Concentration of NAPA in Stool Culture Medium
概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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:
排除标准
- •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.
研究组 & 干预措施
MASLD Group
Patients with metabolic dysfunction-associated steatotic liver disease Participants in this group are adults (18-80 years) with confirmed MASLD based on recent imaging and at least one associated cardiometabolic risk factor. These patients are already monitored in the Endocrinology, Diabetes, and Nutrition Department at Lyon Sud Hospital.
干预措施: stool sampling, dietary assessment, and collection of blood and urine samples (Procedure)
Healthy Volunteers Group
Healthy volunteers meet the general inclusion criteria shared with the patient group but do not present MASLD or other cardiometabolic diseases and do not have any liver pathology.
Their participation serves as a control group for comparison with MASLD patients in the context of the study's biological and metabolic analyses.
干预措施: stool sampling, dietary assessment, and collection of blood and urine samples (Procedure)
结局指标
主要结局
Concentration of NAPA in Stool Culture Medium
时间窗: 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.
次要结局
- Concentration of Selected AAA-Derived Metabolites in Stool Culture Medium(Within 30 days after Visit 1 (sample collection and analysis performed at a single time point))
- Gut Microbiota Composition in Stool Samples(Within 30 days after Visit 1 (sample collection and analysis performed at a single time point))
- Concentration of NAPA in plasma(Baseline Visit 1 (sample collection and analysis performed at a single time point))