ROLIVER - Prospective Cohort for the Identification of Liver Microbiota

Study Overview
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Brief Summary
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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
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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.

Official Title
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ROLIVER - Prospective Cohort for the Identification of Liver Microbiota

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

Intervention / Treatment
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* Procedure: bariatric and other laparoscopic surgery


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: bariatric and other laparoscopic surgery|We have obtained liver samples during laparoscopic surgical procedures in the majority of cases. The majority of laparoscopic procedures were sleeve gastrectomies performed for morbid obesity as a primary restrictive procedure; in 5 cases the liver biopsies were performed during laparoscopic cholecystectomies.|

What is the study measuring?
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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 |