ROLIVER - Prospective Cohort for the Identification of Liver Microbiota (ROLIVER)

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.

Study Overview

• Status: Completed
• Conditions: To Generate Microbial Hypotheses Putatively Responsible for the Onset of Liver Fibrosis
• Intervention / Treatment: Procedure: bariatric and other laparoscopic surgery

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 Type: Observational
• Enrollment (Actual): 36

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Eligible participants were males or females with a BMI over 35 and comorbidities or over 40.

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Tîrgu Mureș Emergency Clinical County Hospital, Romania

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): December 31, 2016
• Study Completion (Actual): January 31, 2017

Study Registration Dates

• First Submitted: April 18, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (Actual): April 30, 2018

Study Record Updates

• Last Update Posted (Actual): April 30, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: TirguMECCH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No