To Generate Microbial Hypotheses Putatively Responsible for the Onset of Liver Fibrosis
Conditions
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.
Interventions
PROCEDUREbariatric 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.
Sponsors
Tîrgu Mureș Emergency Clinical County Hospital, Romania
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Outcome results
None listed