Clinical trial NCT05793190: Gut Mycobiome Profile in Alcoholic Liver Disease.
Official title: Feal Mycobiome Profiling Depending on Alcoholic Liver Disease Severity.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Alcoholic Liver Disease
Lead sponsor: Chuncheon Sacred Heart Hospital
Sponsor class: OTHER
First posted: 2023-03-31
Enrollment: 500
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Total number of 500 participants were enrolled in this clinical trial, out those 500 participants only 120 were met with the inclusion criteria therefore 380 participants were excluded from this clicial trial. Fecal samples were collected prospectively from 120 participants including Healthy Control (HC=20), Alcoholic hepatitis (AH=30), alcoholic cirrhosis (AC=30), Acute-on-Chronic Liver Failure (ACLF=15), Alcoholic cirrhosis (AC=25).

Brief summary: The fecal mycobiome, which refers to the community of fungi that resides in the human gut, is an important component of the gut microbiome. Research has shown that changes in the gut microbiome, including alterations in the fecal mycobiome, may play a role in the development and progression of alcoholic liver disease (ALD).One study published in the journal Gut Microbes found that individuals with ALD had a different gut microbiome composition compared to healthy individuals, including alterations in the levels of certain fungal species. Specifically, the study found that there was an increase in the abundance of the fungal genus Saccharomyces in individuals with ALD. This is significant because Saccharomyces is known to produce ethanol, which can contribute to liver damage in individuals with ALD.Another study published in the journal PLOS One found that there were differences in the levels of fungal metabolites in the fecal samples of individuals with ALD compared to healthy individuals. Specifically, the study found that there were higher levels of certain fungal metabolites, including acetaldehyde and ethanol, in the fecal samples of individuals with ALD.These findings suggest that the fecal mycobiome may play an important role in the development and progression of ALD. Maintaining a healthy gut microbiome through a balanced diet and other lifestyle factors may be an important strategy for preventing and managing ALD, and further research into the role of the fecal mycobiome in this condition is warranted.

Detailed description: Fecal samples were collected prospectively from 120 participants including Healthy Control (HC=20), Alcoholic hepatitis (AH=30), alcoholic cirrhosis (AC=30), Acute-on-Chronic Liver Failure (ACLF=15), Alcoholic Hepatocellular carcinoma (AHCC=25). Mycobial DNA were isolated from collected fecal samples by using DNeasy powersoil pro kit and subjected for nuclear ribosomal RNA internal transcribed spacer (ITS) gene sequencing were performed using the MiSeq sequencer on the illumine platform and based on the phylogenetic relationship, ITS-based Mycobiome Taxonomic Profiling was performed to discovery gut mycobial compositional shift along with ALD severity progression. To discover compositional shift along with ALD severity progression, various statistical analysis method is going to be performed which includes standard mean based differential analysis such ANOVA, Principle component analysis to established the basic compositional variation in all the groups.

Eligibility criteria: Inclusion Criteria:

* Adult patients admitted to Chuncheon Sacred Hallym hospital with a diagnosis of ALD will be screened and potentially recruited.
* ALD patients will be identified based on the recent American Association of the Study of Liver Disease (AASLD) guidelines:

  1. onset of jaundice within 8 weeks,
  2. ongoing consumption of ethanol of \>40 for women or \>60 in men for 6 months or \<60 days of abstinence before onset of jaundice,
  3. Aspartate transaminase (AST\>50), AST:ALT\>1.5 and both \<400 IU/L,
  4. Total bilirubin \>3, or liver biopsy showing histologic features of ALD.

Exclusion Criteria:

* If patients have a history of inflammatory bowel disease, irritable bowel syndrome, gastrointestinal malignancy, or gastrointestinal surgery.
* Patients with acute pancreatitis or history of chronic pancreatitis will also be excluded. The diagnosis of acute pancreatitis and chronic pancreatitis will be ascertained from their history and physical.

Primary outcomes:
measure: Gut mycobiome compositional signature in Alcoholic liver diseases
timeFrame: 2 years
measure: Gut mycobiome biomarkers identification for early detection of decompensated alcoholic liver disease
timeFrame: 2 years
measure: Health beneficial Gut Mycobiome identification in alcoholic liver disease
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Chuncheon
country: Korea, Republic of
facility: Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital
state: Gangwondo
Study officials:
affiliation: Chuncheon Sacred Hallym hospital
name: Ki Tae Suk, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Demir M, Lang S, Hartmann P, Duan Y, Martin A, Miyamoto Y, Bondareva M, Zhang X, Wang Y, Kasper P, Bang C, Roderburg C, Tacke F, Steffen HM, Goeser T, Kruglov A, Eckmann L, Starkel P, Fouts DE, Schnabl B. The fecal mycobiome in non-alcoholic fatty liver disease. J Hepatol. 2022 Apr;76(4):788-799. doi: 10.1016/j.jhep.2021.11.029. Epub 2021 Dec 10.
citation: Hindson J. Distinct faecal mycobiome in patients with NAFLD. Nat Rev Gastroenterol Hepatol. 2022 Feb;19(2):79. doi: 10.1038/s41575-022-00576-z. No abstract available.
citation: Mbaye B, Borentain P, Magdy Wasfy R, Alou MT, Armstrong N, Mottola G, Meddeb L, Ranque S, Gerolami R, Million M, Raoult D. Endogenous Ethanol and Triglyceride Production by Gut Pichia kudriavzevii, Candida albicans and Candida glabrata Yeasts in Non-Alcoholic Steatohepatitis. Cells. 2022 Oct 27;11(21):3390. doi: 10.3390/cells11213390.
citation: Lang S, Duan Y, Liu J, Torralba MG, Kuelbs C, Ventura-Cots M, Abraldes JG, Bosques-Padilla F, Verna EC, Brown RS Jr, Vargas V, Altamirano J, Caballeria J, Shawcross D, Lucey MR, Louvet A, Mathurin P, Garcia-Tsao G, Ho SB, Tu XM, Bataller R, Starkel P, Fouts DE, Schnabl B. Intestinal Fungal Dysbiosis and Systemic Immune Response to Fungi in Patients With Alcoholic Hepatitis. Hepatology. 2020 Feb;71(2):522-538. doi: 10.1002/hep.30832. Epub 2019 Aug 20.
citation: Zeng S, Schnabl B. Roles for the mycobiome in liver disease. Liver Int. 2022 Apr;42(4):729-741. doi: 10.1111/liv.15160. Epub 2022 Jan 17.