Alterations of Gut Microbiota and Metabolites in ALD Patients

Gut Microbiota Clinical Trial

Official title:

Alterations of Gut Microbiota and Metabolites in Asian Patients With Alcohol-associated Liver Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05448144
• Other study ID #: UHCT22032
• Status: Recruiting
• Start date: June 1, 2022
• Est. completion date: December 2024

Study information

• Verified date: August 2023
• Source: Wuhan Union Hospital, China
• Contact: Huikuan Chu, M.D.
• Phone: +8613554105386
• Email: 2012xh0827[@]hust.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Alcohol-associated liver disease is one of the most prevalent liver diseases worldwide, and the leading cause of liver transplantation in the U.S. Alcohol-related liver disease is associated with changes in the intestinal microbiota and metabolites.

Description:

Backgrounds:

Alcohol-associated liver disease (ALD) is a common disease caused by alcohol use disorder (AUD), ranging from asymptomatic liver steatosis to alcohol-associated hepatitis (AH), alcoholic cirrhosis and potentially, hepatocellular carcinoma (HCC). ALD is the most common reason for liver transplantation in the United States. Globally, about 2 million people die from liver disease each year and up to 50% of the death with cirrhosis can be attributed to alcohol consumption. In Europe, it has been estimated that 60%-80% of liver-related deaths can be attributed to alcohol consumption. Currently, the pathogenetic mechanisms have not been fully elucidated, but they might be related to oxidative stress, acetaldehyde-induced toxicity, cytokine and chemokine-induced inflammation. There is no effective therapeutic method for ALD till now except for liver transplantation. Recent studies have reported that gut microbiota has an intimate relationship with ALD, which provides broader insights and opportunities for understanding and treating this disease.

Aims:

We aim to map the alterations of gut microbiota and metabolites in patients with different levels of ALD, and to investigate the effects and mechanisms of key strains and their metabolites on the development of ALD, providing a theoretical basis and potential targets for its treatment.

Methods:

Patients who meet the inclusion criteria will sign informed consent, their demographic data, clinical labs, serum, and feces for shotgun metagenomics will be collected at baseline.

Anticipated Results:

Compared to healthy control group, patients with AH or alcohol-associated hepatic cirrhosis will suffer from microbiota dysbiosis and have more microbes and microbial genes associated with inflammation and fibrosis. Gut microbiota-derived metabolites may exacerbate the severity of ALD. Several microorganisms or metabolites can be used as prognostic markers.

Implications and Future Studies:

Results of altered gut microbiome and metabolites could provide potential targets for manipulating intestinal microbiota to prevent or treat ALD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. The group of ALD:

1. aged >18 years;

2. patients who meet the diagnostic criteria of ALD in Chinese Guideline for the Prevention and Management of Alcoholic Liver Disease (2018 Update);

3. history of chronic heavy alcohol consumption;

4. with relatively complete clinical data and good compliance.

2. The group of purely drinking:

1. aged >18 years;

2. history of chronic alcohol consumption;

3. no evidence of fatty liver, hepatitis or liver injury.

3. The group of healthy control:

1. aged >18 years;

2. without history of alcohol consumption;

3. no evidence of fatty liver, hepatitis or liver injury.

Exclusion Criteria:

1. with hepatocellular carcinoma or hepatic metastases;

2. combined with infectious liver diseases, such as hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus and human immunodeficiency virus (HIV);

3. combined with non-infectious liver diseases, such as non-alcoholic fatty liver disease, drug-induced hepatitis, autoimmune liver disease, Immunoglobulin G subclass 4-related liver disease, Wilson's disease, alpha 1-antitrypsin deficiency, Budd-Chiari syndrome, and other congenital liver diseases;

4. combined with severe organic lesions of other organs;

5. pregnant and lactating women.

Related Conditions & MeSH terms

• Gut Microbiota
• Liver Diseases

Intervention

Other:
• Collect stool and blood samples from patients
Collect stool and blood samples from patients

Locations

Country	Name	City	State
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China

Country where clinical trial is conducted

China, 

References & Publications (5)

Chu H, Duan Y, Lang S, Jiang L, Wang Y, Llorente C, Liu J, Mogavero S, Bosques-Padilla F, Abraldes JG, Vargas V, Tu XM, Yang L, Hou X, Hube B, Starkel P, Schnabl B. The Candida albicans exotoxin candidalysin promotes alcohol-associated liver disease. J He — View Citation

Chu H, Duan Y, Yang L, Schnabl B. Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease. Gut. 2019 Feb;68(2):359-370. doi: 10.1136/gutjnl-2018-316307. Epub 2018 Aug 31. — View Citation

Chu H, Williams B, Schnabl B. Gut microbiota, fatty liver disease, and hepatocellular carcinoma. Liver Res. 2018 Mar;2(1):43-51. doi: 10.1016/j.livres.2017.11.005. Epub 2018 Feb 21. — View Citation

Duan Y, Llorente C, Lang S, Brandl K, Chu H, Jiang L, White RC, Clarke TH, Nguyen K, Torralba M, Shao Y, Liu J, Hernandez-Morales A, Lessor L, Rahman IR, Miyamoto Y, Ly M, Gao B, Sun W, Kiesel R, Hutmacher F, Lee S, Ventura-Cots M, Bosques-Padilla F, Vern — View Citation

Jiang L, Chu H, Gao B, Lang S, Wang Y, Duan Y, Schnabl B. Transcriptomic Profiling Identifies Novel Hepatic and Intestinal Genes Following Chronic Plus Binge Ethanol Feeding in Mice. Dig Dis Sci. 2020 Dec;65(12):3592-3604. doi: 10.1007/s10620-020-06461-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The alterations of gut microbiota in different groups	The alterations will be detected by genome sequencing	When subjects are enrolled
Primary	The alterations of gut metabolites in different group	The alterations will be detected by metabolomics	When subjects are enrolled

External Links

•   This web provides information of Human Subjects Protection in this study