ROLIVER - Prospective Cohort for the Identification of Liver Microbiota

Completed

• Conditions: To Generate Microbial Hypotheses Putatively Responsible for the Onset of Liver Fibrosis

• Registration Number: NCT03511573
• Lead Sponsor: Tîrgu Mureș Emergency Clinical County Hospital, Romania

Brief Summary

The existence of an adipose tissue microbiota causally involved in the triggering of a low grade inflammation could resemble what observed in liver fibrosis. To generate microbial hypotheses putatively responsible for the onset of liver fibrosis we sequenced the 16SrDNA gene from liver biopsies from 36 obese patients (ROLIVER cohort) and describe an original mathematical approach to decipher signatures of early stage of liver fibrosis F0, F1, F2.

Detailed Description

Liver diseases and notably fibrosis are featured by a gut microbiota dysbiosis with a large diversity. Classical statistical analyses does not allow to discriminate between the different low score of liver fibrosis F0,F1,F2. The existence of an adipose tissue microbiota causally involved in the triggering of a low grade inflammation could resemble what observed in liver fibrosis. To generate microbial hypotheses putatively responsible for the onset of liver fibrosis we sequenced the 16SrDNA gene from liver biopsies from 36 obese patients (ROLIVER cohort) and describe an original mathematical approach to decipher signatures of early stage of liver fibrosis F0, F1, F2. We identified that Protebacteria as the main phyla in liver with Pseudomonadaceae and Proteobacteriaceae families representing \~60% of the 16SrDNA gene diversity. While primary component analyses were unable to discriminate between the three groups the partial least square discriminant analysis appears as a powerful tool to identify signatures predictive for each group. We further constructed a matrix of interacting OTU clusters surrounding early scores of liver fibrosis. Eventually, we applied the tfidf approach to exemplify the rare variables which could be carrying some information suitable to refine the diagnosis. Altogether, we here propose a mathematical approach suitable for precise identification of bacteria putatively involve in the progressive development of liver fibrosis that represent hence a new therapeutic opportunity.

Study Timeline

• Study Start: 2014-01-01
• Primary Completion: 2016-12-31
• Study Completion: 2017-01-31
• Status Verified: 2018-04
• Study First Submitted: 2018-04-18
• Study First Submitted QC: 2018-04-18
• Last Update Submitted: 2018-04-18
• Study First Posted: 2018-04-30
• Last Update Posted: 2018-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• bariatric patients
• morbid obesity patients

Exclusion Criteria

• serious chronic associated illness (heart failure, cirrhosis, panhypopituitarism or autoimmune diseases), consumption of alcohol (> 20 g ethanol intake per day), related use of medication (use of laxatives, fiber supplements or probiotics in the previous 6 weeks), inflammatory disorders and use of immunomodulatory drugs. Other exclusion criteria were: history of bariatric surgery, use of anti-obesity drugs in the previous 3 months, recent (last 2 months) or on-going antibiotic use, excessive use of vitamin D supplementation; active or recent (last 3 months), participation in a weight loss program or weight change of 3 kg during the past 3 months, pregnant or planning pregnancy within 6 months or breastfeeding women, drug abuse, and other reasons identified by the Investigator.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
a positive or a negative linear regression between 16SrDNA sequences and liver fibrosis scores	36 months	the frequency of some 16SrDNA in the liver should be positively or negatively correlated with the score of liver fibrosis