Alterations of Gut Microbiota and Metabolites in ALD Patients

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

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.

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.

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.